Production process of mucoadhesitive polymeric nanoparticles with low water content, nanotechnological composition, and their uses

Description

[001] The present invention falls within the areas of aerosol technology and nanotechnology, and relates to a process for obtaining low water content polymeric nanocapsules, as well as obtaining aerosol products, preferably in the form of post-expandable foam, from the pressurization of a suspension of nanocarriers, preferably low water content polymeric nanocapsules, with and without mucoadhesive coating, with and without active substance, for human or veterinary use and with wide industrial applicability in various market segments, mainly pharmaceutical and cosmetic. FUNDAMENTALS OF THE INVENTION

[002] The technology described in the present invention stands out for belonging to the global aerosol market valued at US$40.06 billion in 2024 and expected to reach US$53.13 billion by 2029 at a compound annual growth rate (CAGR) of more than 5.5% from 2024 to 2029, which is primarily driven by product innovation, increased consumption of personal care products, and investments in the medical industry. Although there are several potential markets to absorb the present invention, the pharmaceutical, personal care (personal hygiene, perfumery and cosmetics) and household (household cleaning products) markets stand out.

[003] In the United States of America (USA), aerosol products belong to a significant and growing industry, with an estimated value of 14.18 billion in 2022. The US aerosol market is growing due to the expansion of the personal and home care industry. Petition 870260072434, dated 07 / 21 / 2026, page 6 / 63 2 / 55 The presence of a robust manufacturing base of personal care companies, such as Estée Lauder, Johnson & Johnson, and Procter & Gamble in the US, is considered to have a positive impact that will further boost market demand for aerosols.

[004] Aerosol technology is embedded in the pharmaceutical market, which has focused on the development of aerosol pharmaceutical forms and emerging therapies, such as the pressurized aerosol therapy group. Aerosol products enable convenient and hygienic self-administration of topical pharmaceutical preparations on the skin, body cavities, and mucous membranes, including the vaginal and colorectal areas. Equally important is the incorporation of cutting-edge technologies such as nanotechnology, which allows overcoming obstacles related to unfavorable physicochemical characteristics, low bioavailability, and toxicity, as well as enabling targeted and programmed treatment in the administration of drugs and active substances for the treatment of various diseases.

[005] Brazil is the fourth largest global consumer of aerosols, totaling 1.32 billion units in 2022, with a per capita consumption of 6.5 units. The personal hygiene category (deodorants, antiperspirants, hairspray, shaving foam, hair mousse, nail dryer, among others) represents a significant 66% of this amount. Regarding the personal hygiene, perfumery, and cosmetics market, Brazil ranks fourth among the largest consumers of cosmetic products in the world, according to data from the Brazilian Association of Personal Hygiene, Perfumery and Cosmetics (ABIHPEC). According to data from the aforementioned association, the cosmetics market has been growing at an average of 10% per year, being one of the most dynamic sectors of Brazilian industry, and remains aligned with... Petition 870260072434, dated 07 / 21 / 2026, page 7 / 63 3 / 55 expectations for product development that meet the main global trends in this market. According to Gueisa Silvério, International Business Manager at ABIHPEC, Brazilian companies are betting on active compounds derived from Brazilian biodiversity (63.6% of the products presented had this characteristic), design (57.6% of the products), nanotechnology (48.5% of the products rely on this differential) and sustainable production as differentiators showcased at Cosmoprof Bologna 2022.

[006] Regarding household cleaning products, it is noteworthy that the current relevance of these products was driven by the COVID-19 pandemic, caused by the new coronavirus SARS-CoV-2, allowing cleaning to reach a new level in consumer relations, mainly in relation to awareness of the use of personal antiseptics and the disinfection of environments and surfaces as a public health tool. This fostered the addition and launch of new products to the brands' portfolio, especially aerosol disinfectants, such as 70% alcohol, in addition to research and development of new technologies supported by nanobiotechnology, through the development of nanocarriers (to mitigate transmission) and biosensors (for the rapid diagnosis of the presence of the virus).According to Paulo Engler, Executive Director of the Brazilian Association of Industries of Hygiene, Cleaning and Sanitizing Products for Domestic and Professional Use (ABIPLA): "Brazil is the fourth largest market for sanitizing products in the world and has been playing a leading role in Latin America." According to the 19th edition of the ABIPLA Yearbook (2024), there was a 5.6% growth in the sector's production levels, which reached a turnover of US$ 7.5 billion in 2023. In 2022, the total was US$ 7 billion.

[007] Finally, it is known that the aerosol market is consolidated by nature and, therefore, investment in the development of aerosol products conveying Petition 870260072434, dated 07 / 21 / 2026, page 8 / 63 4 / 55 nanocarriers are attractive and promising, and have a guaranteed consumer market, as they address and reinforce the importance of innovation even within the most traditional and established sectors of this market. STATE OF THE ART

[008] The efficacy and convenience of a topical drug can be strategically improved by reformulating its composition into an aerosol product. As an example, a clinical trial is cited (BlumePeytavi, U. et al. A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women. J. Am. Acad. Dermatol., v. 6, n. 6, p. 1126-1134, 2011) which demonstrated that a single application of 5% minoxidil foam was more effective than the 2% solution in treating androgenetic alopecia in women and men because it increases the absorption of minoxidil by the hair follicles. Concomitantly, a significant reduction in skin irritation was observed with the application of the foam compared to the solution, although the latter was 2.5 times lower.

[009] Another clinical study (Puig, L; Carreterob, G. Update on Topical Treatments for Psoriasis: The Role of Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam. Actas Dermo-Sifiliográficas, v. 110, n. 2, p.115-123, 2019) demonstrated that the drug calcipotriol 0.005% plus 0.064% betamethasone dipropionate (Cal / BD) in aerosol foam has superior efficacy to ointment in the treatment of adult patients with psoriasis vulgaris of the body (trunk and limbs) because the active substances are dissolved in volatile propellants that evaporate when the product is applied to the skin. In this way, a supersaturated foam layer containing Cal / BD is created, allowing greater penetration of the drug through the epidermis. Petition 870260072434, dated 07 / 21 / 2026, page 9 / 63 5 / 55

[010] Despite promising findings, aerosol pharmaceutical forms, by themselves, are not capable of effectively overcoming the obstacles related to the physicochemical characteristics that impact the efficiency and therapeutic efficacy of drugs. Therefore, it is essential to adopt an efficient strategy for delivering drugs at controlled and sustained levels after administration.

[011] Document BR1020120220369 (2012) entitled Finasteride and minoxidil polymeric nanoparticle, preparation process, aqueous suspension containing the same, pharmaceutical composition, and its use, describes a topical pharmaceutical composition preferably containing finasteride and minoxidil nanocapsoids for the treatment of alopecia, enabling the efficient penetration of these drugs into the hair follicles. The document mentions the use of some components that are also part of the composition of the present invention, including the possible use of propylene glycol in the organic phase as a co-solvent. However, propylene glycol is used at a lower concentration, therefore there is no mention of obtaining the low-water-content nanoparticle suspension or of the self-formation of stable aerosol foams for topical administration of active substances.

[012] Document US8460641B2 (2007) entitled Microemulsion process and composition, describes an oil-in-water microemulsion or submicrometer emulsion that can be dispensed as an aerosol foam or mousse whose composition features at least one pharmaceutically active compound, an occlusive agent and one or more dispersed lipophilic surfactants, water, at least one hydrophilic surfactant and a non-surfactant amphiphilic type compound, being characterized as a method of treating corticosteroid-responsive dermatoses. Petition 870260072434, dated 07 / 21 / 2026, p. 10 / 63 6 / 55

[013] Document US9265727B1 (2016) entitled Spray foam corticosteroid product, describes a foamable pharmaceutical composition containing an active compound (clobetasol propionate), a foaming agent, water, a fatty alcohol, a surface-active agent, a buffer, and a propellant contained in a pressurized container for the topical treatment of skin diseases. The difference of the present invention lies in mitigating inconveniences related to the need to invert the container to dispense the foam, the rigidity of the dispensed foam, which may require excessive friction, and the waste involved in dispensing, and the ease of use of the foam on the affected area by the patient.

[014] Pressurized pharmaceutical foams also offer distinct advantages over other pharmaceutical forms intended for vaginal application, mainly because they are able to access the folds of the vaginal mucosa. Regarding rectal administration, enemas are still the main pharmaceutical form used. However, rectal foams are the most tolerated by patients due to convenient administration and minimal discomfort and leakage. Their main advantage is the combination of multidirectional distribution, generally inaccessible with the use of other pharmaceutical forms, and drug penetration after application, allowing the drug to come into intimate and uniform contact with the mucosa, mainly colorectal and vaginal.

[015] Document EP0794767B1 (1958) entitled Stable budesonide solutions, method of preparing them and use of these solutions as enema preparations and pharmaceutical foams, describes stable budesonide solutions dissolved in water, alcohol or a water-alcohol mixture of pH 6.0 or lower. The formulations also contain sodium EDTA, cyclodextrin or mixtures thereof, enabling their preparation and use in pharmaceutical preparations, in particular enemas and Petition 870260072434, dated 07 / 21 / 2026, page 11 / 63 7 / 55 pharmaceutical foams.

[016] Document US8217082B2 (2012) entitled Packaged stable enema solution or suspension containing 5-aminosalicyclic acid, describes a packaged enema comprising a stable suspension of 5-aminosalicylic acid (5-ASA) contained within a substantially oxygen-free liquid carrier medium, said liquid carrier medium having an antioxidant material for the 5-ASA, dispensing with the use of antioxidant agents that are irritating to the colonic mucosa; at least one application bottle containing said dosage suspension disposed in a sealed barrier package, substantially oxygen-free and an oxygen scavenger disposed within said barrier package in order to prevent oxygen migration to said suspension during storage.

[017] Propylene glycol is characterized as a pharmaceutically acceptable carrier according to document US20170112776A1 (2004) entitled Coated controlled release polymer particles as efficient oral delivery vehicles for biopharmaceuticals, which describes a composition that can be formulated as a plurality of nanoparticles or microparticles in vehicles such as glycols and surfactants, namely propylene glycol and TWEEN™ 80, respectively, to produce an edible or inhalable drug.

[018] Document JP2016511268A (2014) entitled Pharmaceutical composition for rectal administration, which describes a pharmaceutical composition for rectal administration in the form of a foam containing fidaxomicin whose aqueous medium comprises a water-soluble alkane, ethanol, polyalcohol, propylene glycol, glycerol, polyethylene glycol, polypropylene glycol or combinations thereof. Petition 870260072434, dated 07 / 21 / 2026, page 12 / 63 8 / 55

[019] Document US3384541A (1964) entitled Spermicidal vaginal pharmaceutical concentrate for producing nonaqueous foam with aerosol propellants, describes a non-aqueous pharmaceutical composition containing a higher proportion of propylene glycol in a lower proportion of an ethoxylated alcohol, being a base composition for the production of pharmaceutical foams including spermicidal preparations that can be applied as an aerosol foam in the vaginal canal. The ethoxylated alcohol acts as a foaming agent, emulsifier, detergent, wetting agent and viscosity former.

[020] The use of propylene glycol in commercially available rectal foam formulations is documented in public assessment reports from drug evaluation committees. Specifically, the medications Salofalk® 1g / dose and Budenofalk® 2mg / dose, produced by the pharmaceutical company Dr. Falk Pharma, are cited. In the Salofalk® aerosol rectal foam, whose active substance is mesalazine (an anti-inflammatory agent used to treat IBD, 5-ASA), propylene glycol enabled the production of foam from a non-aqueous base because mesalazine is insoluble in water within the required pH range. In the Budenofalk® aerosol rectal foam, whose active substance is budesonide (a glucocorticosteroid with a high local anti-inflammatory effect used to treat IBD), propylene glycol conferred self-preservation properties to the medication, thus eliminating the need for preservatives in the final formulation such as sorbic acid.

[021] Rectal administration of budesonide via rectal foams has advantages in terms of convenience of use, but there is the problem of providing budesonide solutions that are stable enough to be delivered as an aerosol. Due to its lipophilicity, budesonide is practically insoluble in water, but is readily soluble in soluble organic alcohols. When using Petition 870260072434, dated 07 / 21 / 2026, page 13 / 63 9 / 55 solubilizers, such as ethyl alcohol, isopropanol, or propylene glycol, allow a sufficient quantity of the active ingredient to be brought into solution. However, solutions obtained in this way are insufficiently stable for pharmaceutical use, since large quantities of the active ingredient decompose in a short time. Regarding mesalazine, which is insoluble in water despite being hydrophilic, its solubility would preclude the production of dense and stable foams, since aqueous suspensions form foams with unfavorable technological characteristics if solvents and emulsifying components were not incorporated.

[022] Some essential characteristics that should be considered in the design of traditional enema and foam formulations stand out, as they can impact their efficiency and effectiveness, including: (i) evaluation of the limiting physicochemical characteristics of suspended or solution-based drugs considering degradation due to pH change, solubility, lipophilicity, photosensitivity, selectivity, adhesion, bioavailability and efficacy; (ii) addition of constituents that enable the maintenance of the formulation's stability, such as EDTA and cyclodextrins; (iii) addition of sulfite compounds and / or other antioxidants that have irritating properties in the intestine, but which are necessary for the stabilization of drugs in suspension such as 5-ASA; (iv) the development of a suspension and its packaging, filling and sealing process free of oxygen and under a nitrogen atmosphere (or other substantially inert gas) increasing the value of the final product; (v) need to thicken the transport vehicle Petition 870260072434, dated 07 / 21 / 2026, page 14 / 63 10 / 55 (water, alcohol or an aqueous-alcoholic fluid) with natural or synthetic thickeners, such as gums, acrylates or modified celluloses; (vi) use of solubilizing agents.

[023] All these limitations can be overcome or mitigated with the use of modern drug delivery technologies such as nanotechnology, which was selected in the present invention aiming at the efficient topical delivery of drugs and active substances mainly, but not exclusively, to the skin, body cavities and mucous membranes, including the colorectal mucosa, for the treatment of IBD. Specifically highlighted is the development of mucoadhesive nanostructured drug delivery systems, aiming to target and increase the residence time of drugs and active substances mainly in human mucous membranes.

[024] The term mucoadhesion was first introduced in 1980 and describes the bioadhesive bond that is established between a mucoadhesive system (non-biological nature) and the mucus layer (biological nature) that coats the surface of mucous membranes in various regions of the body. The incorporation of drugs into nanostructured mucoadhesive systems aims to enhance their efficiency by allowing a longer retention / residence time in the underlying mucosa, leading to an increased concentration gradient that favors drug absorption and localization and increases its local and / or systemic bioavailability (Carvalho et al., 2010; Vijayavani & Maravajhala, 2018). The binding capacity of these nanosystems to mucins determines their mucoadhesive behavior.

[025] Mucoadhesion occurs when a mucoadhesive system (non-biological in nature) adheres to the mucus layer (biological in nature) that lines the surface of the body's mucous membranes. Petition 870260072434, dated 07 / 21 / 2026, page 15 / 63 11 / 55 Chitosan is one of the most widely used cationic adhesive biopolymers in the development of mucoadhesive drug delivery systems due to its biocompatibility, biodegradability, and non-toxicity. Mucoadhesive systems increase the retention time of the active substance in the target mucosa, leading to an increased concentration gradient that favors its absorption, bioavailability, and efficacy.

[026] Documents JP2015520197A (2012) entitled Mucoadhesive nanoparticle delivery system, US9878000B2 (2012) entitled Mucoadhesive nanoparticle composition comprising immunosuppressant and methods of use thereof, US8257740B1 (2011), entitled Pharmaceutical composition of nanoparticles, describe mucoadhesive nanoparticle delivery systems prepared from or coated with chitosan that allow physical interactions of these systems with the inner mucus-secreting layer. However, there is no mention in these and other documents about mucoadhesive nanoparticle systems with low water content in their formulation, preparation method, physicochemical characteristics of both the nanoparticles (after being subjected to the pressurization process) and the technological characteristics of the foams obtained.

[027] Document BRPI0904083B1 (2009) entitled Method for obtaining vesicles (nanocapsules) with a polymeric double layer and positive charge, amphiphilic vesicles with a polymeric double layer and positive charge and their use, describes pharmaceutical and cosmetic compositions containing amphiphilic PCL nanocapsules coated with chitosan capable of simultaneously carrying hydrophilic and hydrophobic actives. The organic phase contains dexamethasone as a lipophilic active, PCL polymer, surfactant and oily vehicle. The aqueous phase contains an ethoxylated hydrophilic surfactant or mixtures thereof, and the coating phase comprises the complex Petition 870260072434, dated 07 / 21 / 2026, page 16 / 63 12 / 55 chitosan-polymyxin B.

[028] The invention CN105407718B (2014) entitled The particle of coating and composition including it, provides a composition that may contain microparticles or nanoparticles encapsulating zinc pyrithione, adapalene, minoxidil, ketoconazole, benzoyl peroxide, sitafloxacin, triclosan, fluconazole, climbazole, clinafloxacin, tetrahydrogen flavin, curcumin, titanium dioxide granules, zinc oxide, chloroxylenol, ascorbic acid or any other combined group. The coating of the particles is carried out with a lipid species, protein and / or cationic molecule such as chitosan. The said composition is indicated for use in compositions of personal care products (shampoo for removing flaking or hair conditioner) and skin care products (creams, gel, toothpaste, mouthwash and chewing gum).

[029] Curcumin (CC), extracted from the root of the Curcuma longa plant, is a naturally occurring flavonoid with pleiotropic characteristics and proven efficacy in the treatment of inflammatory bowel diseases (IBD) in animal models (Epstein et al., 2010; Carrol et al., 2011; Beloqui et al., 2014; Kesharwani et al., 2018) and validated in clinical trials where administration was performed orally and topically (enema) (Beloqui et al., 2014; Singla et al., 2014; Lang et al., 2015; Langhorst et al., 2015; Cheifetz et al., 2017). Furthermore, curcumin is indicated for induction therapy in patients with mild to moderately active ulcerative colitis who do not respond to mesalazine (5-asa) and who do not tolerate dose escalation to immunomodulators or biologics, and is also used in combination with mesalazine in patients who do not respond to oral and / or topical administration (Lang et al., 2015).Furthermore, despite being a multi-target pleiotropic chemopreventive natural agent, curcumin exhibits unique physicochemical characteristics. Petition 870260072434, dated 07 / 21 / 2026, page 17 / 63 13 / 55 unfavorable factors that limit its therapeutic efficacy make it eligible for encapsulation in nanocarriers.

[030] Document CN104414976B (2013) entitled A kind of curcumin nanoparticles and preparation method thereof, describes the preparation of curcumin nanoparticles using the polymer methoxy-polyethylene glycol-polycaprolactone in a ratio of 1 part curcumin to 5-10 parts polymer. The curcumin and polymer are dissolved in an organic solvent which is subsequently removed by evaporation, resulting in a film to which the aqueous phase is added. The curcumin nanoparticles are obtained by filtering the solution with a microporous membrane.

[031] Document CN109010846B (2017) entitled Polyethylene glycol-chitosan-curcumin polymer, drug-loaded nanoparticles thereof and preparation method, describes a formulation of polyethylene glycol-chitosan-curcumin nanoparticles whose purpose is to encapsulate or conjugate hydrophobic or anticancer active substances. The preparation is carried out in six steps and involves the reaction of curcumin with succinic anhydride, activation of the carboxyl group of carboxylated polyethylene glycol, reaction of the activated carboxyl group with acetic acid solution containing chitosan and curcumin, for 48–96 hours under a protective gas atmosphere, and subsequent purification.

[032] Document CA2952335A1 (2016) entitled Therapeutic delivery formulations and systems comprising cannabinoids and terpenes, describes rectal enemas comprising o / w emulsions whose active ingredients (cannabinoids and terpenes) of the formulation are delivered in emulsions and preferably in microemulsions and nanoemulsions.

[033] Document EP2578209A1 (2011) entitled Nanoparticulate composition containing antibiotics for intramammary administration in animals, describes two types Petition 870260072434, dated 07 / 21 / 2026, p. 18 / 63 14 / 55 of polymeric nanocapsules, including mucoadhesive ones, to encapsulate various drugs such as benzathine cloxacillin for veterinary purposes, including the treatment of mastitis in dairy cattle via intramammary administration. This document states that its colloidal dispersions are prepared by the interfacial deposition method of a pre-formed polymer followed by displacement with water-miscible and oil-immiscible solvents and hydrophobic polymers. The polymer poly-βcaprolactone (PCL) and low molecular weight chitosan are used to obtain mucoadhesive nanocapsules with a size and zeta potential of 291 nm and +16 mV, respectively, and an encapsulation efficiency of 87%. In contrast, the PCL nanocapsules coated with low molecular weight chitosan of this patent were prepared by self-assembly using the pre-formed polymer interfacial deposition technique (Fessi et al., 1989; Bender et al., 2012) and exhibited superior physicochemical characteristics with a size and zeta potential of 212.6 ± 3.1 nm and +23.6 ± 0.2 mV, respectively, and an encapsulation efficiency of 99%.

[034] Currently, there is no patent document that mentions the inherent nanotechnological characteristics of the mucoadhesive polymeric nanocapsules described in the present invention, namely: the use of the PCL polymer and its chitosan coating in obtaining nanocapsule suspensions produced with low water content, differentiating them from classic colloidal suspensions. Nor is it mentioned whether it is possible to obtain and maintain the stability of colloidal systems developed in a dispersed medium consisting of water and polyol, as proposed in the present invention. Furthermore, there is no mention describing the possibility of altering the surface properties of low-water-content mucoadhesive nanocapsules such as those proposed in the present invention, easily enabling the modification or functionalization of the surface of the Petition 870260072434, dated 07 / 21 / 2026, page 19 / 63 15 / 55 nanoparticles, which is a desirable characteristic for site-directed drug delivery.

[035] Regarding the route of administration, there is no patent document yet that discusses the rectal administration of mucoadhesive polymeric nanocapsules, including those with low water content such as those proposed in this document, that are capable of nanoencapsulating, including, natural active substances and, in particular, curcumin. It is also noteworthy that there are no patent documents that mention obtaining other types of low water content nanocarriers, preferably coated with chitosan, as described in the present invention. Since, for absorption to occur, drugs need to be able to penetrate the mucus layer to reach the epithelium of the cells lining the mucosa, including the colorectal mucosa, impacting the bioavailability and efficacy of the active substance.

[036] Another aspect of the present invention is an aerosol product, but not exclusively, in the form of a post-expandable foam obtained from the pressurization of a suspension of low-water-content polymeric nanocapsules coated (mucoadhesive) or uncoated with a biopolymer, such as chitosan. This nanotechnology platform can be used, but not exclusively, for pharmaceutical purposes aimed at administering drugs and active substances to the skin, body cavities and mucous membranes.

[037] Aerosol foams have several advantages when administered to the skin, body cavities, or mucous membranes. On the skin, the less compact structure of the foam allows for easier spreading, as well as the ability to cover a large area with a relatively small amount of liquid. In body cavities and mucous membranes, especially vaginal and colorectal, the main advantage of the foam is the significant increase in Petition 870260072434, dated 07 / 21 / 2026, page 20 / 63 16 / 55 its volume after application, allowing drugs and active substances to come into closer contact with the target mucosa. In addition, they allow for comfortable self-administration, influencing patient adherence to the proposed treatment.

[038] Despite the aforementioned advantages, commercially available aerosol foam formulations are scarce. This is partly due to the stabilization of a composition in aerosol foam form and the high cost of the technology. Regarding patent documents describing aerosol products for human or veterinary use, it is noteworthy that there are no pharmaceutical compositions or products with technology equivalent to that presented in the present invention.

[039] The vagina has a self-cleaning system, continuous vaginal flow, which, combined with the law of gravity, reduces the residence time of active substances inside the vaginal cavity. Thus, mucoadhesion is a fundamental characteristic for a drug delivery system in the vaginal cavity. Documents US3384541A (1964) entitled Spermicidal vaginal pharmaceutical concentrate for producing nonaqueous foam with aerosol propellants; US005314904A (1992) entitled Pharmaceutical compositions containing rifaximin for treatment of vaginal infections; JPH0984855A (1995) entitled Aerosol preparation for administer medicine to rectum or vagina and US8226972B2 (2002) entitled Vaginal delivery of drugs, US20170231909A1 (2017) entitled Foam prepared from nanoemulsions and uses, address the topical administration of pharmaceutical compositions in foam form for the treatment of local conditions or for use in contraception.

[040] Document US8795635B2 (2008) entitled Substantially non-aqueous foamable petrolatum based Petition 870260072434, dated 07 / 21 / 2026, page 21 / 63 17 / 55 pharmaceutical and cosmetic compositions and their uses, refers to stable, non-aqueous, non-alcoholic, non-silicone foaming vehicle compositions comprising petrolatum or mixtures thereof and at least one foaming agent. When water is present, the foaming composition may be an emulsion, microemulsion, or nanoemulsion. In contrast to the present invention, the low-water nanotechnology platform composition is self-foaming after being subjected to a pressurization process without the need for at least one surfactant or foaming agent. It is also noteworthy that the present invention has polymeric nanocapsule-type nanocarriers, which are more stable in physiological media when compared to nanoemulsions.

[041] US patent application US11219631B2 (2010) entitled Foamable compositions, breakable foams and their uses, describes a substantially surfactant-free foamable composition containing a short-chain alcohol, water, polymer, fatty alcohol or fatty acid or a combination of fatty alcohol and fatty acid and propellant. In one or more embodiments, the active agent is encapsulated in particles, microparticles, nanoparticles, microcapsules, microspheres, nanocapsules, nanospheres, liposomes, niosomes, polymer matrix, silica gel, graphite, nanocrystals or microsponges.

[042] Document AU2005204341A1 (2005) entitled Body cavity foams, describes an alcohol-free foam composition for application to a body cavity or mucosal surface containing at least one organic carrier, a polar solvent, an emollient and mixtures thereof, at least one surfactant, at least one bioadhesive polymeric agent, a gelling agent, a film-forming agent and a liquefied or compressed propellant gas. The compositions also have at least one active agent carried on nanoparticles. Petition 870260072434, dated 07 / 21 / 2026, page 22 / 63 18 / 55 with a diameter of 200 nm to 400 nm.

[043] Document WO2014135891A1 (2014) entitled Pharmaceutical composition for rectal administration, refers to an aerosol pharmaceutical composition for rectal administration in the form of a foam comprising fidaxomicin and the actives in manometric form having an average particle size less than or equal to about 2,000 nm, preferably less than or equal to about 1,000 nm.

[044] It is noteworthy that the present invention enables the encapsulation of active substances in nanocarriers, preferably of the type of polymeric nanocapsules coated with chitosan, providing them with mucoadhesive capacity that allows the drug to be directed and accumulated preferentially in mucous membranes, including the colorectal mucosa. Since chitosan increases the bioadhesiveness of the nanoparticles due to non-covalent interactions (ionic interaction and hydrogen bonds) with mucin chains, which is the main and major constituent protein of mucus, which has a negative charge, increasing the residence time and, consequently, the effectiveness, due to intimate contact between the nanoencapsulated active ingredient and the target mucosa.

[045] Document US20220142921A1 (2015) entitled Enema for rectal application, describes an enema containing budesonide for rectal application in liquid or foam form, to be administered at 1.5 to 2.5 mg of budesonide twice daily for 6 weeks, aiming at the treatment and prevention of recurrence of inflammatory bowel disease. The foam was prepared from a solution of budesonide dissolved in alcohols, and also includes a preservative, emulsifier and an aqueous solution containing EDTA. Finally, the resulting solution can be delivered as an aerosol, in a single or multiple dose device, the propellant gas of which is preferably a hydrocarbon such as Petition 870260072434, dated 07 / 21 / 2026, page 23 / 63 19 / 55 isobutane, n-butane, or a mixture of propane and n-butane.

[046] The present invention overcomes limitations and disadvantages identified in the aforementioned patent documents by enabling the vectorization of hydrophobic drugs and active substances in low-water-content mucoadhesive polymeric nanocapsules capable of targeting, accumulating, and increasing the residence time in mucous membranes, including the colorectal mucosa, due to the mucoadhesive coating of the nanocarriers with chitosan. This avoids the use of solubilizing agents such as ethyl alcohol, isopropanol, or propylene glycol, and their insufficiently stable solutions for pharmaceutical use, since large quantities of non-nanoencapsulated actives decompose in a short time. It also avoids other agents such as chelating agents or antioxidants, allowing a reduction in the amount of irritating constituents in the formulation. Additionally, the nanotechnology platform is self-foaming after being subjected to a pressurization process.

[047] Document US20170231909A1 (2017) entitled Foam prepared from nanoemulsions and uses, comprises a foam obtained from a foamable oil-in-water nanoemulsion that includes oil nanoglobules, a stabilizing agent, a nonionic surfactant, an ionic surfactant or a polymeric agent, a liquefied or compressed propellant gas, water and other compounds. Intended for topical administration to treat, relieve or prevent disorders of the skin, body cavity or mucous surface.

[048] Document JP2018506554A (2016) entitled Nanoparticle Composition, describes a topical nanoparticle composition of a water-soluble and water-sensitive active substance or a pharmaceutically acceptable salt that does not contain water. In one of its preferred embodiments, the topical nanoparticle composition is a foam or Petition 870260072434, dated 07 / 21 / 2026, p. 24 / 63 20 / 55 aerosol, the non-aqueous liquid vehicle is a silicone and / or mineral oil fluid, there is at least one blowing agent and one surfactant. In addition to a non-aqueous vehicle (which may act as a foam disintegrant), there is at least one rheology modifier and one propellant. In contrast, the present invention also allows the delivery of drugs, active substances and / or cosmetic actives carried in a suspension of adaptable low-water nanocarriers, either by the possibility of obtaining various types of low-water nanostructures; or by the possibility of performing a mucoadhesive coating or by functionalizing the surface of the low-water nanostructures, and these characteristics were not described in the aforementioned document. The nanotechnology platform proposed in the present invention enables the administration of water-insoluble drugs and active substances by various routes of administration, including the rectal route.Furthermore, it has the ability to self-form good quality foams after being subjected to the pressurization process, which eliminates or mitigates the concern of maintaining a balance with foam-forming excipients such as those described in this document.

[049] Document US20210023226A1 (2020) entitled Surfactant-free, water-free foamable composition and breakable foams and their uses, describes a substantially surfactant-free and foaming agent-free foam composition that includes a hydrophobic solvent, a model active ingredient (Tetracycline), a wax and a propellant. In one or more other embodiments, when the active ingredient is partially soluble or insoluble, it is presented as a suspension or may be encapsulated in particles, microparticles, nanoparticles, microcapsules, microspheres, nanocapsules, nanospheres, liposomes, niosomes, polymeric matrix, silica gel, graphite, Petition 870260072434, dated 07 / 21 / 2026, page 25 / 63 21 / 55 nanocrystals or microsponges. However, as cited in the aforementioned document, although some active compounds are effectively inert in the described compositions, other active compounds are very sensitive to degradation and can react, break down, or easily reorganize.

[050] In the pharmaceutical market, there are not many topical aerosol products available for application to the skin, mucous membranes, and body cavities, especially aerosol foams. Furthermore, the available products do not contain nanocarriers in their composition, such as: • NitroMist® 0.4 mg, every 4 or 5 minutes, up to 3 doses, Evus Pharmaceuticals: used in acute attacks and prophylaxis of angina. Drug: nitroglycerin. • Oluxfoam® 0.05%, Stiefel Laboratories: indicated for the treatment of moderate to severe plaque psoriasis of the scalp and mild to moderate plaque psoriasis of body regions outside the scalp. Drug: clobetasol propionate. • Epifoam® 1% / 1% / 10g, Meda Pharmaceutis®: used to relieve inflammatory manifestations and itching of skin conditions responsive to corticosteroids (dermatoses). Drug: pramoxine hydrochloride and hydrocortisone acetate. • Salofalk® 1 g / 30 ml, Dr. Falk Pharma: used in the treatment of active and mild ulcerative colitis of the sigmoid colon and rectum. Drug: mesalazine. • Budenofalk® 2mg / 25ml, Dr. Falk Pharma: used in the early treatment of Crohn's disease and ulcerative colitis. Drug: Budesonide. • Cortifoam® / Colifoam® 10% / 15g, Alaven Pharmaceutical LLC: used for the topical treatment of nonspecific ulcerative colitis located in the rectal and proctosigmoid area. Drug: hydrocortisone acetate. Petition 870260072434, dated 07 / 21 / 2026, page 26 / 63 22 / 55 • Predfoam® 20mg / 30ml, MPT Pharma Ltd.: used in the topical treatment of ulcerative colitis and proctitis. Drug: prednisolone.

[051] It is also noteworthy that there are no documents describing low-water-content mucoadhesive colloidal systems that can be applied in the locoregional administration of drugs by pressurized aerosol therapy (PAT) in foam form, in addition to therapies derived from, but not limited to, pressurized intraperitoneal aerosol chemotherapy (PIPAC), pressurized intraperitoneal aerosol chemotherapy by electrostatic precipitation (ePIPAC), pressurized intrathoracic aerosol chemotherapy (PITAC), pressurized intraluminal aerosol chemotherapy (PILAC), pressurized intravesical aerosol chemotherapy (PIVAC), pressurized intrarectal aerosol chemotherapy (PIRAC), hyperthermic intraperitoneal chemotherapy (HIPEC), and others.

[052] Documents EP3750523A1 (2019) entitled Active substance delivery system; DE212020000727U1 (2019) entitled Composition with drug-containing micro-nanoparticles of an anti-cancer drug and EP3791865A1 (2019) entitled Active substance delivery system with delayed delivery, describe suspensions of drug delivery systems, preferably chemotherapeutic drugs, in nanocarriers that can be synergistically combined with the PAT technique, preferably PIPAC, including for veterinary use, but these do not have any similarity with the technological characteristics described in the present invention. Furthermore, these inventions preferentially highlight their application in the local treatment of peritoneal carcinomatosis resulting from cancer of gynecological or gastrointestinal origin.

[053] Documents WO2021092666A1 (2019) entitled Petition 870260072434, dated 07 / 21 / 2026, page 27 / 63 23 / 55 Ultrasound aerosolization platform for the application of therapeutic substances in body cavities and EP3427781A2 (2018) entitled Drug and device system for pressurized aerosol therapies into a mammalian hollow space, characterize the term nanoparticles as an active agent in liquid form to be administered to humans and animals from aerosolization platforms.

[054] In view of the foregoing, the present invention overcomes the limitations, disadvantages and even the advantages described in the available patent documents by enabling an innovative nanotechnology platform in the pharmaceutical and medical field in terms of: (i) to obtain a novel nanotechnology application that enables, after being subjected to a pressurization process, the production of aerosol products in the form of a post-expandable foam; (ii) to obtain a nanotechnology platform applicable to the locoregional administration of drug nanocarriers administered by pressurized aerosol therapy technology in the form of foam; (iii) to obtain targeted, intelligent and programmable low water content nanocarriers for a wide variety of purposes; (iv) to the use of low water content nanocarriers containing active substances of natural origin such as curcumin; (v) to the technological development of an ideal dynamic system for topical drug delivery to the skin, body cavities or mucous membranes, including colorectal and vaginal; (vi) to the rectal route for the administration of colloidal systems in the form of aerosol foam Petition 870260072434, dated 07 / 21 / 2026, page 28 / 63 24 / 55 aimed at treating diseases affecting the colorectal mucosa.

[055] In view of the above, it is also worth highlighting that aerosol products carrying nanocarriers have a guaranteed consumer market, since they reinforce and meet the importance of innovation even within the most traditional and established sectors of the market.

[056] Furthermore, the polymeric nanocapsules proposed in the present invention are novel in the literature because they were obtained from the direct pressurization of a drug delivery system that uses water, derived from the nanoparticle suspension, and propylene glycol, in combination as a vehicle. In contrast, classic polymeric nanocapsule suspensions have a 100% aqueous external phase, making it impossible to obtain a dispersed system in the form of an aerosol foam, since pure liquids do not form stable and high-quality foams. Additionally, there are no reports in the literature of nanocapsules, mucoadhesive nanocapsules, or low-water-content mucoadhesive nanocapsules administered for the topical drug delivery of drugs, active substances, or cosmetic actives.

[057] This invention is characterized as a solution to classic polymeric nanocapsule suspensions, which have an aqueous external phase making it impossible to obtain a dispersed system in the form of aerosol foam, since pure liquids do not form stable and good quality foams. Furthermore, propellants of the hydrocarbon class, such as butane, when pressurized within the aerosol are found as a highly lipophilic liquefied fluid. In this liquefied state, these propellants behave as an oily phase. Therefore, the proposed solution differs Petition 870260072434, dated 07 / 21 / 2026, p. 29 / 63 25 / 55 considerably reduces the effectiveness of classic nanocarrier suspensions by presenting a component that preferentially replaces 25% of the water quantity. However, concentrations above or below the aforementioned concentration are also within the scope of the present invention. SUMMARY OF THE INVENTION

[058] The present invention relates to obtaining aerosol products, preferably in the form of post-expandable foam, from the pressurization of a suspension of nanocarriers, preferably low water content polymeric nanocapsules, with and without mucoadhesive coating, with and without active substance, for human or veterinary use and with wide industrial applicability in various market segments, mainly pharmaceutical and cosmetic.

[059] In a first aspect, the present invention provides a nanometric composition consisting of low water content polymeric nanocapsules.

[060] In a second aspect, the present invention provides a mucoadhesive nanometric composition consisting of low-water-content polymeric nanocapsules containing curcumin and coated with chitosan.

[061] In a third aspect, the present invention provides an aerosol nanotechnology platform obtained from the pressurization of low water content polymeric nanocapsules.

[062] In a fourth aspect, the present invention provides a nanotechnology platform in the form of an aerosol foam consisting of low-water-content polymeric nanocapsules containing curcumin and coated with chitosan.

[063] In a fifth aspect, the present invention provides an aerosol nanotechnology platform comprising a Petition 870260072434, dated 07 / 21 / 2026, page 30 / 63 26 / 55 Pharmaceutically acceptable formulation intended for topical treatment of skin, body cavities and mucous membranes, including vaginal and colorectal. In one embodiment, this product is intended for the treatment of inflammatory bowel diseases via the rectal route.

[064] In a sixth aspect, the present invention provides a nanotechnology platform that can be applied to the locoregional administration of drugs by aerosolized and pressurized foam therapy.

[065] In a seventh aspect, the present invention provides a nanotechnology platform that can be applied in innovative processes and technologies aimed at obtaining medical devices and products. BRIEF DESCRIPTION OF THE FIGURES

[066] Figure 1 shows nanocapsule distribution profiles obtained by laser diffraction and PCS techniques of NCC-CH (A and B, respectively) and NCC (C and D, respectively) suspensions (n=3).

[067] Figure 2 shows TEM photomicrographs of uncoated low-water-content curcumin nanocapsules (NCC) at magnifications of 100,000x (A) and 300,000x (B) and chitosan-coated low-water-content curcumin nanocapsules at magnifications of 100,000x (C) and 300,000x (D) (NCC-CH) (n=3).

[068] Figure 3 presents a schematic of the main characteristics found in the LNC-CC, NCC and NCC-CH nanocapsule suspensions in Fourier transform infrared spectroscopy.

[069] Figure 4 shows the results of ultracentrifugation in the presence of a Percoll® density gradient. A: low water content nanocapsules coated with chitosan without (NB-CH) and B: with curcumin (NCC-CH), C: Petition 870260072434, dated 07 / 21 / 2026, p. 31 / 63 27 / 55 low water content chitosan-coated nanocapsules containing curcumin after 60 days of storage / stability (NCC-CH, 60 days), D: low water content coated nanodispersion without drug (ND-CH), E: chitosan-coated lipid nanoemulsion without drug (NE-CH) and F: chitosan-coated lipid nanosphere without drug (NES-CH) (n=3).

[070] Figure 5 shows the characteristics of the foam from an aerosol enema containing chitosan-coated, low-water-content curcumin nanocapsules. A: metal containers / aerosol packaging; B: characteristic of the foam formed and C: aerial view of the foams produced (n=3).

[071] Figure 6 presents the morphology analysis from TEM photomicrographs of low water content curcumin nanocapsules coated with chitosan (NCC-CH) at magnifications of 300,000x (A) before (NCCCH) and after pressurization of the nanocapsules present in post-expandable aerosol rectal enema foam (FNCC-CH) at magnifications of 100,000x (B) and 300,000x (C).

[072] Figure 7 shows the characteristics of the foam from an aerosol enema containing low-water-content curcumin nanocapsules coated with chitosan containing a foaming agent. A: metal containers / aerosol packaging; B: characteristic of the foam formed and C: aerial view of the foams produced (n=3).

[073] Figure 8 presents the morphology analysis from TEM photomicrographs of low water content curcumin nanocapsules coated with chitosan (NCC-CH) at 300,000x magnification (A) before and after pressurization of the nanocapsules present in post-expandable aerosol rectal enema foam containing the foaming agent polysorbate 80 (FNCC-CHT) at 100,000x magnification (B) and 300,000x magnification (C) (n=3). Petition 870260072434, dated 07 / 21 / 2026, page 32 / 63 28 / 55

[074] Figure 9 presents the evaluation of the mucoadhesive properties obtained by the washability test of low water content curcumin nanocapsules uncoated at pH4 (NCC at pH4) and coated with chitosan at pH4 and pH6 (NCC-CH at pH4 and NCC-CH at pH6, respectively) (n=3).

[075] Figure 10 presents the evaluation of mucoadhesive properties obtained by texturometer (n=6). DETAILED DESCRIPTION OF THE INVENTION

[076] The present invention relates primarily to a process for producing low-water-content polymeric nanocapsule-type nanoparticles containing curcumin and coated with chitosan, prepared by self-assembling using the pre-formed polymer interfacial deposition technique.

[077] It should be noted that the present invention also allows the production of other types of low-water-content nanostructures, such as, for example, nanospheres and nanoemulsions coated and uncoated with chitosan or another mucoadhesive coating agent. However, preferably, the present invention is directed towards obtaining low-water-content polymeric nanocapsule-type nanostructures coated with chitosan, i.e., mucoadhesive, obtained by the pre-formed polymer deposition technique. It is noteworthy that other techniques for producing low-water-content nanoparticles can be used to obtain said nanocapsules or other types of low-water-content nanostructures, including those with functionalized surfaces or coated with other polymers.

[078] The aforementioned process comprises the following steps: (a) Formation of the organic phase; Petition 870260072434, dated 07 / 21 / 2026, page 33 / 63 29 / 55 (b) Formation of the aqueous phase; (c) Injection of the organic phase into the aqueous phase; and (d) Coating of the nanocapsules.

[079] The steps of the process carried out will be described in more detail below.

[080] First, curcumin and at least one hydrophobic polymer, a fixed oil, an organic compound, a phospholipid, and a low HLB (Hydrophilic-Lipophilic Balance) surfactant were dissolved in an organic solvent and a co-solvent to form the organic phase. In contrast, the aqueous phase is formed by dissolving at least one hydrophilic surfactant, preferably neutral, in water.

[081] More precisely, for the formation of the organic phase, the polymers poly(s-caprolactone) (PCL, Mn 10,000 — Mw 14,000 g.mol-1) (0.100 g), caprylic / caprylic triglyceride (0.165 mL), sorbitan monostearate (0.0385 g), propylene glycol (6 mL), lecithin (0.9 g) and curcumin (0.010 g) were dissolved in acetone (24 mL) and ethanol (3 mL). This organic phase was injected under constant magnetic stirring into the aqueous phase containing polysorbate 80 (0.0770 g) and ultrapure water (54 mL).

[082] The aqueous phase, which must be prepared in parallel, contains at least two surfactants for the preparation of the mucoadhesive polymeric nanocapsules of this invention. One of the surfactants must be neutral and hydrophilic, preferably, but not exclusively, polysorbate 80, although polysorbate 20, polysorbate 60, macrogol stearate, macrogol cetostearyl ether, macrogol lauryl ether, macrogol oleyl ether, macrogol oleate, polyoxyl castor oil, hydrogenated polyoxyl castor oil, and mixtures thereof may also be used. The other must preferably, but not exclusively, be a surfactant of Petition 870260072434, dated 07 / 21 / 2026, page 34 / 63 30 / 55 class of polyoxygenated polymers, such as lecithin.

[083] After 10 min, the organic solvents were evaporated under reduced pressure at 40 °C and the suspension was concentrated to a final volume of 10 mL. These curcumin-containing compositions were designated NCC. In addition, blank formulations characterized by the absence of curcumin were prepared for control purposes and designated NB. All formulations were produced in triplicate.

[084] Subsequently, the low water content nanocapsules obtained at 40 °C were subjected to tests using different concentrations of low molecular weight chitosan coating solutions (50 to 190 kDa — 75 % to 85 % degree of deacetylation) in order to make them mucoadhesive.

[085] Among the concentrations tested, the 0.75% (w / v) solution provided the highest positive surface potential and, therefore, this concentration was selected for coating purposes. This solution was slowly added to the low-water nanocapsule suspension under constant and moderate magnetic stirring for a period of 2 hours. After this, the nanoparticle suspension was named NCC-CH. In addition, blank formulations with chitosan coating were prepared in triplicate for control purposes and named NB-CH. All formulations were produced in triplicate.

[086] In the present invention, propylene glycol was selected because it is a water-miscible organic solvent possessing important physicochemical characteristics such as a boiling point above 120 °C, low vapor pressure, preservation effect, stability of the foam structure, and compatibility with the components of the developed nanotechnology platform, in addition to its corrosion inhibition properties. Additionally, other non-polar aliphatic alcohols containing 2 to 12 carbon atoms, Petition 870260072434, dated 07 / 21 / 2026, page 35 / 63 31 / 55 but not only these, the following can be used, such as: ethylene glycol, butylene glycol, glycerol which are particularly useful in dynamic foam formulations.

[087] In other embodiments, the vehicle for the nanocapsules of the present invention may also include a stabilizing component such as a nonionic surfactant, a polymeric agent, or a mixture of a nonionic surfactant and a polymeric agent. The nonionic surfactants may be used as individual components and in combinations, which may be added to the composition in concentrations sufficient to achieve a desired foamability, in addition to being able to promote steric stabilization of the nanocapsules at the air-liquid interface.

[088] The polymer used to produce the shell of the curcumin-containing nanocapsule of the present invention is preferably, but not limited to, poly(s-caprolactone) (PCL, Mn 10,000 - Mw 14,000 g.mol-1) and its derivatives. Other synthetic or natural, biodegradable or biocompatible polymers such as polylactic acid and its derivatives, polylactic-co-glycolic acid and its derivatives, polyglycolate and its derivatives, methacrylates and their derivatives; and / or natural polymers such as chitosan, as well as other polymeric materials not previously mentioned, may be used. The present invention encompasses a wide variety of polymers that can be used alone or in combination in a wide range of concentrations.

[089] The oil used in the organic phase of the preparation of the polymeric nanoparticles of this invention is preferably, but not limited to, synthetic oils including medium-chain triglycerides, such as capric and caprylic acids. Mineral oils (aliphatic aromatic) may also be used. Petition 870260072434, dated 07 / 21 / 2026, pp. 36 / 63 32 / 55 saturated or unsaturated, cyclic or non-cyclic) and natural (grape seed oil, canola oil, soybean oil, olive oil, copaiba oil, as well as other oils including essential oils). The oil concentration to be used ranges from 0.0001 to 30% (v / v).

[090] The lipophilic surfactant employed in the organic phase of preparation of the mucoadhesive polymeric nanoparticles of the present invention is a low HLB surfactant, preferably with a value in the range of 3 to 6, being liquid or solid, preferably solid, selected from the group consisting of sorbitan monostearate, sorbitan distearate, sorbitan tristearate, caprylocaproyl macrogolglycerides, propylene glycol laurates, propylene glycol caprylates, glyceryl monostearate, polyglyceryl oleates, or mixtures thereof. Preferably, the lipophilic surfactant used in the organic phase of the invention is sorbitan monostearate.

[091] The solvent used in the organic phase of the preparation of the polymeric nanoparticles of the present invention is preferably, but not limited to, acetone. However, other solvents exhibiting physicochemical properties of intermolecular interaction with water may be used, such as dimethyl sulfoxide, dimethylformamide, N-methylpyrrolidone, dioxane, acetonitrile, methyl ethyl ketone. The co-solvent used in the organic phase of the preparation of the polymeric nanoparticles of this invention is preferably, but not limited to, ethanol. However, methanol, ethanol, propanol, and isopropanol, or other alcohols, mono-, di-, tri-, or polyhydroxylated, glycerol, sorbitol, polyethylene glycol, mannitol may also be used.

[092] Additionally, the present invention proposes a composition comprising at least (a) a suspension of Petition 870260072434, dated 07 / 21 / 2026, page 37 / 63 33 / 55 low-water-content mucoadhesive nanocapsules, (b) at least one nanoencapsulated active substance and / or drug, and (c) liquefied propellant; (d) a foamable vehicle. In one aspect, the foam composition includes a foamable vehicle comprising the mucoadhesive nanocapsule suspension itself having an average particle diameter of less than 1000 nanometers, preferably between 100 and 400 nm, before and after being subjected to the pressurization process.

[093] Butane was the propellant gas used to pressurize the compositions of this invention. However, the propellant can be any pharmaceutically acceptable gas, such as other isolated hydrocarbons and their mixtures (e.g., isobutane, propane and / or butane), hydrochlorofluorocarbons, hydrofluoroalkanes and compressed gas. These propellants can be used alone or in combination. Preferably, the propellant comprises a mixture of n-butane, isobutane, propane.

[094] The propellant has an important influence on the properties of the foam, such as the extent of expansion (expansibility) and the collapse time of the bubbles. Good foam expansibility is desirable for greater reach in the desired action locations. In this invention, butane hydrocarbon was used as the propellant, which was selected because it is the only propellant gas option available in the city of Porto Alegre - Rio Grande do Sul, Brazil. In some embodiments, a combination of propellants from the hydrocarbon family may be used. Likewise, other types of aerosol propellants such as hydrofluorocarbons and / or compressed gas may be used.

[095] The selected concentration of butane gas was evaluated by assessing foam formation and expansion. The ideal concentration tested for the conditions of this Petition 870260072434, dated 07 / 21 / 2026, page 38 / 63 34 / 55 The invention involved using 28 g of butane for 50 mL of formulation in a 100 mL metal container (the smallest volume container available from the company). Lower propellant concentrations produce foams with unsatisfactory characteristics. The propellant exerts pressure on the aerosol can and the fluid phase within it, which is always greater than atmospheric pressure. This pressure depends on the composition and concentration of the propellant in the system and is normally in the range of 2 to 4 bar (Arzhavitina & Steckel, 2010). In this invention, the pressure inside the aerosol can using 28 g of butane gas was 2.27 bar, which is within the recommended range for these dynamic systems.

[096] The composition proposed in the present invention preferably does not include a preservative. However, it may optionally contain preservatives and / or combinations thereof. Likewise, it may include polymeric agents, preferably, but not limited to, a bioadhesive, gelling, film-forming agent and / or a phase-change agent, or combinations thereof. In other embodiments, it may also comprise the addition of a liquid wax containing at least one fatty alcohol. Likewise, it may also include a combination of liquid and solid waxes. In some other embodiments, all the aforementioned agents may be present in the composition at a concentration of about 0.0001%.

[097] Liquid wax comprises one or more free fatty acids, primarily oleic acid, linoleic acid, palmitoleic acid, others, or a mixture of any two or more of these.

[098] Solid wax mainly comprises a fatty acid, a fatty alcohol, a microcrystalline wax, a petroleum wax, a polyethylene wax, a beeswax, Petition 870260072434, dated 07 / 21 / 2026, pp. 39 / 63 35 / 55 castor wax, tallow, wool wax and a mixture of any two or more of these or others; and also a solid wax selected from the group consisting of stearic acid, cetyl alcohol, behenyl alcohol, stearyl alcohol, cetostearyl alcohol and a mixture of two or more of these or others.

[099] To obtain the composition, the aforementioned low-water-content mucoadhesive nanocapsule (NCC-CH) suspensions were then pressurized with the selected propellant, according to conventional techniques, and packaged in appropriate packaging, being designated FNCCCH. In one embodiment, the present invention includes a mucoadhesive nanocapsule suspension essentially free of surfactant (FNCC-CH). In another embodiment, the foam composition further comprises the addition of surfactant to the external phase of the suspension, being designated FNCC-CHT. In some other embodiments, the present invention may include nanoparticles with a functionalized surface, preferably with metal ions and / or antibodies.

[100] The foams obtained were characterized as dense, translucent, and white in color for foams whose composition consisted of low-water-content polymeric nanocapsules without curcumin, and yellow for those containing nanoencapsulated curcumin. The foam's expansibility was evaluated after a volume of foam was propelled from the metal container, observing its subsequent expansion. The good expansibility observed in the obtained foams can also be attributed to butane gas. In general, hydrocarbons are usually selected as propellants due to their ability to generate foams with greater expansion height and duration, thus influencing foamability (Mei et al., 2017).

[101] Foam formation leads to a large increase Petition 870260072434, dated 07 / 21 / 2026, pp. 40 / 63 36 / 55 of the surface area of ​​a liquid and consequently corroborates a high surface free energy. In this context, the addition of foaming agents in foam formulations is interesting because they reduce the surface tension of water, stabilize the foams, and prevent bubble coalescence. Despite the aforementioned importance, the formulation developed in this work differs from what is found in the literature by prioritizing a composition free of foaming agents.

[102] The NCC-CH suspension, which originated the foams, presented a high viscosity of 72.66 ± 3.25 cP, being characterized as a non-Newtonian pseudoplastic fluid with a yield value due to the presence of propylene glycol, which positively increases the retention time of the foam enema in the colonic mucosa, in addition to potentially reducing losses related to the formulation expelled after intrarectal administration. Hari et al. (2015) found apparent viscosity values ​​ranging from 2.2 ± 0.5 to 2.5 ± 0.4 mPas for aerosol foams containing efavirenz nanoparticle suspensions aimed at the topical and sustained release of this drug via the vaginal route.Given the scarcity of scientific publications focused on the development of aerosol foams containing nanoparticle suspensions, it is important to mention data related to the viscosity of other pharmaceutical forms obtained from pressurization, such as smart in situ gel aerosol foams.

[103] The applicability of the obtained nanocapsules was evaluated in the pharmaceutical field for the topical administration of active substances such as curcumin, since it has unfavorable absorption, distribution, metabolism and excretion (ADME) characteristics due to low solubility, instability at neutral and alkaline pH values, high metabolism rate and low Petition 870260072434, dated 07 / 21 / 2026, page 41 / 63 37 / 55 bioavailability limits its therapeutic potential (Beloqui et al., 2014).

[104] The present invention also allows the isolated or combined use of various active agents, such as, for example, a substance of natural origin with a drug, two or more substances of natural origin, drugs and cosmetic actives and their combinations. Concentrations of curcumin above or below that specified in the present invention are also within the scope of the present invention, as are the various optional configurations of the combination of active agents. Examples of embodiments of the invention Example 1. Development of low water content uncoated and chitosan-coated nanocapsules

[105] Low water content lipid core nanocapsules were prepared by self-assembly using the pre-formed polymer interfacial deposition technique (Fessi et al., 1989; Bender et al., 2012). At 40 °C, poly(ecaprolactone) (PCL, Mn 10,000 - Mw 14,000 g.mol-1) (0.100 g), caprylic / caprylic triglyceride (0.165 mL), sorbitan monostearate (0.0385 g), propylene glycol (6 mL), lecithin (0.9 g) and curcumin (0.010 g) were dissolved in acetone (24 mL) and ethanol (3 mL). This organic phase was injected under constant magnetic stirring into the aqueous phase containing polysorbate 80 (0.0770 g) and water (54 mL). After 10 min, the organic solvents were evaporated under reduced pressure at 40°C and the suspension was concentrated to a final volume of 10 mL. Blank formulations without curcumin were also prepared for control purposes, designated NB. All formulations were produced in triplicate.

[106] Subsequently, the low-water-content nanocapsules obtained were subjected to coating tests with three concentrations of chitosan coating solutions. Petition 870260072434, dated 07 / 21 / 2026, pp. 42 / 63 38 / 55 low molecular weight (50 to 190 kDa - 75% to 85% degree of deacetylation) at 0.35, 0.5 and 0.75% (w / v) in 1% aqueous acetic acid solution. Among them, the 0.75% (w / v) solution provided the highest positive surface potential and, therefore, this concentration was selected for coating purposes. This solution was slowly added to the low water content nanocapsule suspension under constant and moderate magnetic stirring for a period of 2 hours. This formulation containing curcumin was named NCC-CH. Blank formulations with chitosan coating were also prepared in triplicate for control purposes and named NB-CH (Figure 1). Example 2. Physicochemical characterization of the produced nanocapsules 2.1 pH Determination

[107] pH determination was performed using a DM-22 calibrated potentiometer (Digimed, Brazil) directly on the formulation. Measurements were performed in triplicate and results expressed as mean ± standard deviation. 2.2 Determination of particle diameter and polydispersity

[108] The diameter and size distribution of the nanoparticles were initially evaluated by laser diffraction using the Mastersizer® 2000 equipment (Malvern Instruments, UK) in order to verify if the particles are restricted to the nanometer range. Subsequently, after confirmation, the average diameter and polydispersity index were complementarily determined by dynamic light scattering (Zetasizer® nano-ZS model ZEN 3600, Malvern) after appropriate dilution of the dispersions in ultrapure water. The measurements were performed in triplicate and the results expressed as mean ± standard deviation. Petition 870260072434, of 21 / 07 / 2026, p. 43 / 63 39 / 55 padrão (Bernardi et al., 2009; Sutthanut et al., 2009).

[109] Nanoparticle tracking analysis (NTA) was also performed to evaluate the size and concentration distribution of low-water-content nanoparticles considering the range of 10 to 1000 nm. (NanoSight LM 10 and NTA 3.2 Analytical Software, NanoSight Ltd., Amesbury, United Kingdom) (Filipe et al., 2010). White, curcumin-containing, low-water-content nanocapsule formulations were diluted (10,000 times) and subsequently injected into the sampling chamber cell of the equipment. The sampling chamber was coupled to an optical microscope with 20x magnification, and a red laser beam (638 nm) was focused on the sample, over which a video camera was positioned. Images of the particles in Brownian motion were captured by the camera in a 10s video file.The results obtained were determined using software to identify and track the light individually scattered by the nanoparticles by the arithmetic mean in six-fold increments ± standard deviation of the calculated sizes and concentrations of all samples analyzed. 2.3 Zeta potential

[110] The zeta potential was determined using the electrophoresis technique (Zetasizer® nano-ZS model ZEN 3600, Malvern) after dilution of the suspensions (500 times, v / v) in 10 mM NaCl solution previously filtered through a 0.45 pm membrane. Measurements were performed in triplicate and the results expressed as mean ± standard deviation. 2.4 Viscosity

[111] The viscosity of chitosan-coated, low-water-content nanocapsule suspensions containing curcumin was determined using a Brookfield rotational viscometer (LVDV-II + Pro) fitted with an attached ULA spindle. Petition 870260072434, dated 07 / 21 / 2026, pp. 44 / 63 40 / 55 in a circulating water bath at 25°C ± 1°C. Analyses were obtained using 16 mL of sample, with varying speeds from 2 to 13 rpm, a time of 60 seconds, and 10 reading points. The flow profiles of non-Newtonian fluids were characterized using four mathematical models: (1) Bingham, for values ​​indicative of plastic viscosity (η0); (2) Casson, for values ​​indicative of viscoelasticity; (3) Power Law, for values ​​indicative of flow index; and (4) Herschel-Bulkley for values ​​indicative of rupture points or yield strength (ρΔ). The model with the fit value (%) closest to 100% was chosen as the one that best describes the flow profile of the formulations. Shear stress and strain rate data were obtained using Brookfield Rheocalc software version 3.2. The measurements were performed in triplicate and the results are expressed as mean ± standard deviation. τ = To + ηγ (Equation 1) τ0·5 = to0·5 + η0.5γ0.5 (Equation 2) τ = MYn (Equation 3) τ = to + KYn (Equation 4) 2.5 Transmission electron microscopy

[112] The morphology of the developed nanocapsules was evaluated by transmission electron microscopy using a JEM 1200 Exll model, JEOL, Japan (TEM). For this analysis, the suspensions were previously diluted 1:10 (v / v) in pre-filtered ultrapure water (0.45 μm) and deposited on copper grids (400 mesh) coated with formvar-carbon. Uranyl acetate solution (2%, w / v) was used as a negative contrast. After preparation, the samples remained in a desiccator for 24 hours at room temperature for subsequent analysis (Figure 2). Petition 870260072434, dated 07 / 21 / 2026, pp. 45 / 63 41 / 55 2.6 Fourier Transform Infrared Spectroscopy (FTIR)

[113] The FTIR technique was used to verify the formation of chemical bonds between components of the low-water nanocapsules with the dispersing medium composed of a combination of propylene glycol and water. All nanostructured formulations were analyzed in a Fourier transform infrared spectrometer (640-IR FTIR®, Varian, USA). Potassium bromide pellets were obtained using a hydraulic press (Auto-CrushIR®, PIKE Technologies, USA) applied 3.5 Tm to each pellet. The spectra obtained were recorded in transmission mode in a range of 4000 to 400 cm-1 with a resolution of 4 cm-1 in 32 scans (Figure 3). 2.7 Curcumin content and encapsulation efficiency in nanocapsules

[114] Curcumin was quantified by high-performance liquid chromatography (HPLC) on a Shimadzu® HPLC system model LC-20A (LC-20AT pump, SPD-M20A photodiode array detector (PDA), CBM-20A system controller, SIL-20A autosampler (Tokyo, Japan)) and a Phenomenex RPGemini C18 (150 x 4.6 mm, 5 μm) with a Gemini C18 precolumn). The mobile phase was prepared using Milli-Q® water and HPLC-grade acetonitrile and consisted of acetonitrile:water acidified with 0.5% acetic acid (53:47 v / v). The flow rate used was 0.7 mL / min and the injection volume was 20 μL. The HPLC method was validated, showing linearity between 10 and 50 μg / mL-1, (y = 47843x - 43742, inter- and intraday variability less than 2.0%, detection and quantification limits of 0.09 μg / mL and 0.31 μg / mL, respectively. Detection occurred at a wavelength of 360 nm and the retention time was 9.9 minutes. The parameters used in the validation process (linearity, precision, specificity, accuracy) Petition 870260072434, dated 07 / 21 / 2026, pp. 46 / 63 42 / 55 and the limit of quantification and detection) are in accordance with the requirements of ANVISA's RDC 166 / 2017 (Brazil, 2017).

[115] The encapsulated curcumin content was determined after dissolving the nanocapsules in acetonitrile:water acidified with 0.5% (v / v) acetic acid and subsequent filtration (Millipore 0.45 μL) and quantification by HPLC. The encapsulation efficiency (EE%) was calculated (Equation 5) by determining the total drug (Ct) in the nanocapsules and the free curcumin concentration detected in the ultrafiltrate (Cl) obtained by the ultrafiltration-centrifugation technique (Ultrafree Microcon 10000 MW, Merck Millipore, Darmstadt, Germany), at 5000 rpm for 10 min (Equation 5). %EE=——— x 100 (Equation 5) .8 Density gradient study - Percoll® [11 6] Density gradient evaluation was performed to determine the density of low-water-content chitosan-coated nanocapsules (NB-CH) and curcumin-containing nanocapsules (NCC-CH) developed and, mainly, to evaluate the presence of other types of nanostructures (Figure 4). Thus, the evaluated formulations, described below, were prepared and coated according to the particularities of each formulation as described in example 1: 1. Low-water-content chitosan-coated nanocapsules without drug (NB-CH); 2. Low-water-content chitosan-coated nanocapsules containing curcumin (NCC-CH); 3. Drug-free, low-water-content coated nanospheres (NE-CH); 4. Drug-free coated lipid nanoemulsion (NEL-CH) (polymer-free); Petition 870260072434, dated 07 / 21 / 2026, page 47 / 63 43 / 55 5. Drug-free coated nanodispersion (ND-CH) (using exclusively sorbitan monostearate and polysorbate 80); 6. Low water content chitosan-coated nanocapsules containing curcumin (NCC-CH60) after 60 days of refrigerated storage (5 ± 2 °C).

[117] Initially, band calibration was performed using markers of different known densities (Beads®) that were added to Percoll® for external band calibration. Band heights were measured using a caliper positioned from the meniscus to the midpoint of each of the samples under evaluation. The density of the formulations was determined using a polynomial curve (y= 0.00006x2+ 0.0048x + 0.9838) determined by plotting the distance from the meniscus versus the observed density for each band of the markers - Beads®. To each suspension described above (0.4 mL) a gradient of 54% v / v Percoll® colloidal silica in 150 mM NaCl (19.6 mL) was added, which were subsequently subjected to ultracentrifugation. Finally, particle separation was performed, and the initial density of the marker (1.074 g / mL) formed in situ during ultracentrifugation using a PS28T rotor (CP80WX Hitachi, Japan) at 20 °C and 45°F was used as a reference.000xg for 60 min (Jager et al., 2009; USP, 2014). 2.9 Stability study when stored in a refrigerator

[118] Low-water-content curcumin nanocapsule suspensions coated with chitosan (NCC-CH) and uncoated (NCC) were evaluated for their stability under refrigeration storage (5 ± 2°C / 100 days) at predetermined times during 0, 7, 15, 30, 60, 45, and 100 days. During the execution of this study, the Petition 870260072434, dated 07 / 21 / 2026, pp. 48 / 63 The following parameters were evaluated: particle size distribution and average particle diameter, polydispersity index, zeta potential, and pH. The dosage and association rate of curcumin with the nanoparticles were quantified using HPLC (Example 2, Section 2.7). Measurements were performed in triplicate and the results expressed as mean ± standard deviation. 2.10 Evaluation of the in vitro release profile

[119] The in vitro release assessment was performed using the dialysis bag method, in which release profiles were obtained in terms of the percentage of curcumin released as a function of time. The release medium used was a simulated colonic fluid consisting of Na2HPO4 and KH2PO4 without enzymes / ethanol (70:30 v / v) which was adjusted with phosphoric acid to pH 4 ± 0.5, in order to mimic the diseased colon affected by IBD (Jain A & Jain SK, 2008). The dialysis bags (12,000 to 14,000 Da cutoff, Sigma-Aldrich) used were made of cellulose and were filled with low-water nanocapsule suspensions and free curcumin solution in methanol, and individually immersed in containers containing 80 mL of the aforementioned delivery medium in order to simulate in vivo conditions.Agitation and temperature (37 ± 0.5 °C) were controlled, and at predetermined times, 1 mL aliquots of the release medium were collected, filtered (0.45 μm Millipore® filters), and quantified by HPLC using a previously described method. After the volume was removed, it was replaced with 1 mL of new release medium. The in vitro release profiles of curcumin from the nanocapsules and the free solution versus time were plotted in Microsoft Office Excel®, and subsequently, mathematical modeling was performed using semi-empirical models (zero-order equation, first-order monoexponential equation, and first-order biexponential model) using Scientist® 2.0 software. Petition 870260072434, dated 07 / 21 / 2026, pp. 49 / 63 45 / 55 (Micromath®, USA), in order to evaluate the release mechanism of free and encapsulated curcumin (Zanotto-Filho et al., 2013; Coradini et al., 2015; Paese et al., 2017). Example 3. Development of post-expandable rectal enema foam in aerosol form containing low-water-content curcumin nanocapsules coated with chitosan.

[120] The aerosol enema foam was obtained through a service contract with an aerosol product packaging company called Aeromag (Porto Alegre, Rio Grande do Sul). The packaging process used 45 mL of the produced nanocapsule suspension (Example 1) and 28 g of butane propellant gas supplied by Liquigás. The metal containers (0.52 x 112 cm) used had a varnished inner coating and were purchased from Cerviflan (Guarulhos, São Paulo). The packaging process at Aeromag is carried out using self-built stainless steel packaging machines consisting of a transfer pump to draw and pressurize the gas, a liquid gas dosing pump, and a product dosing pump. All formulations were produced in triplicate, including the control formulations without curcumin, called the blank formulation (Figure 5). Example 4. Physicochemical characterization of post-expandable rectal enema foam in aerosol containing low-water-content curcumin nanocapsules coated with chitosan. 4.1 Foam structure, bubble size and shape

[121] The size and shape of the bubbles in the foams obtained were evaluated macroscopically immediately after spraying the aerosol formulation into a glass container (Zhao et al., 2010b; Hari et al., 2015; Ramyadevi & Rajan, 2015). Petition 870260072434, dated 07 / 21 / 2026, pp. 50 / 63 46 / 55 4.2 Bubble Collapse Time

[122] The bubble collapse time refers to the time required for the air bubbles to completely disappear from the formulation, leaving only the drained liquid containing the nanocapsules on the surface where the foam was applied. For this evaluation, three foam sprays were performed in beakers and the decrease in the foam column was visually assessed at predetermined times. 4.3 Relative density of the foam (DR)

[123] The relative density of the foam (DR) was estimated by distributing the foam in a petri dish with an approximate volume of 60 mL and then the weight of this set was measured on an analytical balance. Similarly, the mass of the same volume of water was determined and the relative density of the foam (DR) was calculated using equation 6. mass of the foam test sample (mass of the same volume of water, equation) 4.4 Evaluation of nanocapsule morphology after pressurization

[124] This evaluation was performed by transmission electron microscopy as described in example 2, section 2.5 (Figure 6). 4.5 Evaluation of the addition of a nonionic foaming agent to the external phase of the formulation

[125] Polysorbate 80 (1.5 g), a non-ionic foaming agent, was added to the external phase of the formulation. The new foams obtained, containing white, low-water-content nanocapsules and chitosan-coated curcumin-containing nanocapsules with added foaming agent, were named FNB-CHT and FNCC-CHT, respectively (Figure 7). The physicochemical characterization of these nanoparticles was performed according to the techniques described previously. Petition 870260072434, dated 07 / 21 / 2026, pages 51 / 63 47 / 55 (Figure 8). Example 5. Study of the mucoadhesive properties of nanocapsule suspension and aerosol foam in vitro. 5.1 Washability Profile

[126] The mucoadhesive potential of low-water-content coated curcumin nanocapsules and free curcumin at different pH levels was evaluated by the washability test. This assay was conducted in a modified Franz diffusion cell, featuring an inlet and outlet channel for the washing solution, coupled to a flow pump (Bonferoni et al., 1999; Rossi et al., 1999; Frank et al., 2014; Zatta et al., 2018). The receiving medium and washing fluid consisted of a buffer containing disodium phosphate and monopotassium phosphate at pH 4.0 ± 0.5 and pH 6.0 ± 0.5 acidified with phosphoric acid in order to mimic the colonic pH during an acute IBD attack and the healthy colon, respectively. The experiment was conducted in a thermostatically controlled bath (37 ± 1 °C) with moderate agitation. The sigmoid colon mucosa of a pig was used as a model membrane, separating the acceptor medium from the receptor medium, and was provided by Frigorífico Ouro do Sul (Harmonia - RS).The intestine was received whole, and then the portion corresponding to the sigmoid colon was separated. The colonic mucosa was detached with the aid of a scalpel and then cleaned with ultrapure water, the outer surface was gently dried, and it was individually wrapped in aluminum foil and stored under refrigeration at -20°C.

[127] Before starting the experiment, the mucosa was removed from refrigeration and kept at room temperature for 30 min for subsequent cell assembly. After assembly, the cells were kept for 30 minutes under temperature and agitation of the receptor medium to reactivate the mucosa. After this period, 200 was added to the mucosa. Petition 870260072434, dated 07 / 21 / 2026, pages 52 / 63 48 / 55 pL of curcumin-containing nanocapsule suspension. After 30 min of contact, a washing flow of 0.5 mL / min was initiated. At predetermined times over 480 min, the washed medium was collected and subjected to the previously standardized extraction process for subsequent quantification of curcumin by HPLC (Figure 9).

[128] After the experiment was completed, the formulation adhered to the mucosa was collected using cotton, and the mucosa used in the cell was reduced to small pieces; and, subsequently, both were subjected to the same extraction process, separately, for quantification of curcumin adsorbed and penetrated into the mucosa, respectively. Finally, the receptor medium was collected and filtered to evaluate the concentration of permeated curcumin. As a specificity control, the formulation without curcumin, the blank formulation, was used. In order to evaluate the resistance to washing flow by the developed formulation and to evaluate the behavior of the developed formulation in a healthy colon, the experiment was also carried out at pH 6. The experiment was also conducted with a free curcumin solution for comparison purposes. 5.2 Mucoadhesion work

[129] The mucoadhesive properties of the formulations were evaluated using a texture analyzer (TA.XT plus; Stable Microsystem, Godalming, UK), using the Mucoadhesive Test method. Analyses were performed in sextuplicate for the NCC and NCC-CH formulations. First, porcine colonic mucosae were obtained and prepared for this assay. At the base of the equipment, a heating plate was maintained at a temperature of 32 °C to maintain the temperature of the analyzed sample. An aliquot of the sample (600 µl) was placed in a transparent support, Petition 870260072434, dated 07 / 21 / 2026, pages 53 / 63 49 / 55 flat bottom. At the end of the probe (10 mm in diameter), coated with adhesive tape, the membrane was adhered, completely covering the surface, and then hydrated with 3 drops of ultrapure water at a temperature of 32 °C for 1 min, and the excess liquid was removed with absorbent paper. At a height of 50 mm, the probe was lowered at a speed of 2 mm / s until it came into contact with the formulation, applying a minimum force of 0.200 N to ensure contact for 600 seconds. After this period, the probe was withdrawn at the same descent speed to the initial stage (Figure 10).

[130] In this context, the collapse time and stability of the developed foam can also be attributed to the delay in drainage rate due to an increase in viscosity caused by the presence of propylene glycol in the formulation of the nanocapsule suspension that originates the foams, the amount of which used does not seem to have affected the balance between viscosity and surface elasticity of the film formed due to the large expansibility and long duration observed in the foam formed.

[131] Additionally, drainage kinetics and other foam destabilization mechanisms may have been reduced by the presence of low-water-content polymeric nanocapsules containing curcumin coated with chitosan on the gas-liquid interface surface of the liquid films. Since foams stabilized by nano- and microparticles alone are much more stable than foams stabilized with polymers or surfactants (Martinez et al., 2008).

[132] The pH of the nanocapsule suspension remained unchanged (0.45 ± 0.00) after the pressurization process. The relative density found was 0.02 ± 0.00 and 0.03 ± 0.00 for the foams containing white nanocapsules and with Petition 870260072434, dated 07 / 21 / 2026, pages 54 / 63 50 / 55 curcumin, respectively. Hari et al. (2015) found apparent density values ​​of 0.06 ± 0.07 for an aerosol foam containing a suspension of efavirenz nanoparticles aimed at the topical and sustained release of this drug via the vaginal route. In contrast, Ramyadevi & Rajan (2015) obtained apparent density values ​​ranging from 0.06 ± 0.0 to 0.07 ± 0.0. Karthick et al. (2018) obtained relative density values ​​for the foam in the range between 0.035 and 0.056.

[133] Scanning electron microscopy (TEM) photomicrographs revealed that the spherical morphology of the low water content nanocapsules present in FNCC-CH remained preserved, in addition to having shown low polydispersity after the suspensions were subjected to the pressurization process.

[134] The average curcumin content in the NCC-CH formulations before and after pressurization (renamed FNCC-CH) was 95.1 ± 0.65% and 92.6 ± 0.65%; and the encapsulation efficiency was 99.3% and 96.7%, respectively. From these results, it can be inferred that the content and association rate of curcumin did not change after the pressurization process.

[135] In the particle size analysis, using the laser diffraction technique, the existence of a micrometric population in FNCC-CH equivalent to 3.29% was observed after the pressurization process, which can be attributed to physical-chemical destabilization processes in the foam occurring at the gas-liquid interface (Hari et al., 2015; Ramyadevi & Rajan, 2015).

[136] The average z-diameter of the nanocapsule suspensions (NCC-CH) was initially 228 ± 10.8 nm, and after pressurization (FNCC-CH) showed a significant increase (p<0.05) in the average diameter, becoming Petition 870260072434, dated 07 / 21 / 2026, pages 55 / 63 51 / 55 342 ± 18.0 nm, therefore there was an increase of 150%. Corroborating the average diameter results, there was also an increase (p<0.05) in the polydispersity index of FNCC-CH, whose average value varied from 0.22 ± 0.0 to 0.32 ± 0.0 after the pressurization process.

[137] Thus, polysorbate 80 (1.5 g), a non-ionic foaming agent, was added to the external phase of the formulation. The new formulations were named FNB-CHT (white low-water nanocapsules coated with chitosan) and FNCC-CHT (white low-water nanocapsules containing curcumin coated with chitosan). The foams obtained from FNB-CHT and FNCC-CHT were characterized as dense, translucent, and white and yellow in color, for those containing nanocapsules without and containing curcumin, respectively.

[138] The NCC-CH suspension after the addition of the foaming agent polysorbate 80 showed a reduction in viscosity from 72.66 ± 3.25 cP to 25.13 ± 0.25 cP, but maintained the rheological behavior of a pseudoplastic non-Newtonian fluid that also fit the Herschel-Bulkley mathematical model. Photomicrographs obtained by TEM revealed that the spherical morphology of the low-water-content nanocapsules present in FNCC-CHT remained preserved and showed low polydispersity after the addition of polysorbate 80 to the external phase of the formulation after being subjected to the pressurization process.

[139] The average z-diameter of the FNCC-CH was 342 ± 18 nm; and after the addition of the foaming agent to the formulation, and subsequent pressurization, the average diameter obtained was 303 ± 32 nm (FNCC-CHT). Thus, no significant reduction in this parameter was observed after the addition of polysorbate 80, although there was a reduction from 150% to 133% in the average diameter when compared with the NCC-CH. Petition 870260072434, dated 07 / 21 / 2026, pages 56 / 63 52 / 55 (228 ± 32.3 nm). Furthermore, laser diffraction showed that even after the addition of the foaming agent, the micrometric population persists; however, the foaming agent acted significantly (p<0.05) in reducing the average percentage of the micrometric population detected in the formulations after 10 days.

[140] The results obtained from the polydispersity were 0.032 ± 0.0 and 0.29 ± 0.0 for FNCC-CH and FNCC-CHT, respectively, demonstrating that the foaming agent polysorbate 80 did not have a significant effect on this evaluated parameter, corroborating the results of the average diameter z-average. Regarding the zeta potential, polysorbate 80 did not promote a significant positive impact (p<0.05) by increasing it in the FNCC-CHT nanocapsules, whose absolute value was +29.86 ± 2.64 mV when compared to FNCC-CH (+27.8 ± 2.5 mV). Therefore, the zeta potential did not change after the formulations containing polysorbate 80 were subjected to the pressurization process, as previously mentioned.

[141] The addition of polysorbate 80 to chitosan-coated low-water nanocapsule suspensions resulted in a statistically significant impact (p<0.05) on the reduction of the micrometric population. This finding may be attributed to greater stabilization, possibly by steric action, which limited the aggregation of nanocapsules at the air-liquid interface.

[142] The mucoadhesive properties of the post-expandable aerosol foam obtained and of the NCC and NCCCH suspensions from which it originated were evaluated in vitro by determining the work of mucoadhesion in a texture analyzer (TA.XT Plus Texture Analyzer) using porcine colonic mucosa as a model. In this experiment, the force (mN) required to detach the mucosa from the samples was evaluated. Petition 870260072434, dated 07 / 21 / 2026, pp. 57 / 63 53 / 55 tested, as well as the distance (mm) traveled until complete detachment. The result of the area under the curve of the force versus distance graph gives us the value of the mucoadhesive work (WMA - mN.mm-1) exerted to break the bond between the mucosa and the mucoadhesive material (Andrews et al., 2009; Zatta et al., 2018).

[143] The NCC and NCC-CH suspensions did not show significant differences between themselves in the parameters evaluated. In contrast, the aerosol foam showed statistically significantly higher values ​​(p<0.05) of the force required for detachment, as well as the distance traveled until this feat, resulting in a higher WMA compared to the other samples analyzed. It is inferred, therefore, that the developed aerosol foam increased the mucosa-biopolymer interaction resulting in a WMA 2x higher when compared to the NC and NCC-CH suspensions. This result can be attributed mainly to the foam's ability to increase the surface area of ​​a liquid, due to the presence of mucoadhesive nanocapsules with high zeta potential present in the aerosol foam, which in themselves are able to remain in contact with the mucosa for much longer; and to the viscosity of the thin liquid films provided by the presence of propylene glycol in the formulation (Malarvizhi et al., 2014; Hari et al., 2015; Ramyadevi & Rajan, 2015).

[144] Finally, the unprecedented and relevant outcomes presented reveal valuable scientific evidence, but also intrinsic challenges that require further research to confirm the scalability of obtaining safe, effective and high-quality topical aerosol drug delivery systems containing nanostructures with unique properties provided by the nanoscale. Applications of the Invention

[145] The composition developed in the present invention Petition 870260072434, dated 07 / 21 / 2026, pages 58 / 63 54 / 55 has numerous applications, among which we can mention: - Application in different types of industries, mainly pharmaceutical and cosmetic, constituting an innovation in the development of low water content nanostructured systems and their use in the production of different types of aerosol products; - Nanoencapsulation of drugs from various pharmacological classes intended for the treatment of various diseases, active substances and / or cosmetic actives, synthetic or natural, isolated or in combination. - application of aerosol therapy (AAT), such as: pressurized intraperitoneal aerosol chemotherapy (PIPAC), pressurized intraperitoneal aerosol chemotherapy by electrostatic precipitation (ePIPAC), pressurized intrathoracic aerosol chemotherapy (PITAC), pressurized intraluminal aerosol chemotherapy (PILAC), pressurized intravesical aerosol chemotherapy (PIVAC), pressurized intrarectal aerosol chemotherapy (PIRAC), hyperthermic intraperitoneal chemotherapy (HIPEC) and others; - locoregional treatment of diseases, such as peritoneal carcinomatosis, ovarian cancer, colorectal cancer and others, for human or veterinary use. In particular, the present invention can be used in the treatment of cancer / tumor, including its metastatic forms; - Topical treatment of ulcerative colitis, ulcerative proctitis, and Crohn's disease. - Topical treatment via rectal administration of disorders and diseases affecting the human colon, such as inflammatory bowel diseases; Petition 870260072434, dated 07 / 21 / 2026, pp. 59 / 63 55 / 55 - Production of aerosol pharmaceutical forms intended primarily for the topical treatment of skin, mucous membranes, and body cavities; - Applicability targeted towards pharmaceutical purposes for human or veterinary use; - Applicability in innovative processes and technologies in the healthcare field; - Applicability in innovative processes and technologies aimed at obtaining medical and dental devices such as orthotics, prosthetics, special materials, and others; - Applicability in innovative processes and technologies aimed at obtaining medical and dental products in all their categories, such as medical equipment, materials for use in healthcare, and in vitro diagnostic products; - as an auxiliary tool and / or health products and / or equipment, mainly microneedles, spray devices, atomizers, angio-injectors, injection pumps or any combination thereof, preferably with a nebulizer or nebulization platform, spray gun or spray catheter.

[146] The present description aims to elaborate on the inventive concept, provide examples that facilitate its understanding, and provide precise technical data on some of the ways to implement it. It should be noted that the examples provided and illustrated in this description aim to clarify some of the ways to carry it out, but should not be interpreted as limiting the scope of the invention.

Claims

1. Process for producing low-water-content mucoadhesive polymeric nanoparticles characterized by being self-assembling, comprising the following steps: (a) Formation of the organic phase by dissociation of curcumin and at least one hydrophobic polymer, a fixed oil, an organic compound, a phospholipid, and a low HLB (Hydrophilic-Lipophilic Balance) surfactant in an organic solvent and a co-solvent; (b) Formation of the aqueous phase by dissolving at least one hydrophilic surfactant, preferably neutral, in water; (c) Injection of the organic phase into the aqueous phase; and (d) Coating the nanocapsules with low molecular weight chitosan solutions; wherein said low-water-content nanoparticles are selected from the group consisting mainly of nanocapsules, nanospheres, and nanoemulsions, preferably nanocapsules.

2. Process according to claim 1, characterized in that in step (a) preferably poly(ε-caprolactone) (PCL, Mn 10,000 - Mw 14,000 g.mol-1), caprylic / caprylic triglyceride, sorbitan monostearate, propylene glycol, lecithin and curcumin are dissolved in acetone and ethanol.

3. Process according to claim 1, characterized in that in step (b) at least two surfactants, one of which is selected from the group of neutral and hydrophilic surfactants consisting mainly of polysorbate 80, polysorbate 20, polysorbate 60, macrogol stearate, macrogol cetostearyl ether, macrogol lauryl ether, macrogol oleyl ether, macrogol oleate, polyoxyl castor oil, hydrogenated polyoxyl castor oil, and mixtures thereof, and the other preferably selected from the group of polyoxygenated polymers consisting preferably of lecithin, are dissolved in ultrapure water.

4. Process according to claim 1, characterized in that in step (d) the nanocapsules are coated with a low molecular weight chitosan solution of 50 to 190 kDa, and a degree of deacetylation of 75% to 85%.

5. Nanotechnological composition characterized in that it comprises: (a) at least one suspension of low-water-content mucoadhesive polymeric nanocapsules as obtained in any of claims 1 to 3 having an average particle diameter of less than 1000 nanometers, preferably between 100 and 400 nm; (b) at least one nanoencapsulated active substance and / or drug; (c) liquefied propellant; and (d) a foamable vehicle; wherein said composition consists of a post-expandable aerosol foam; and wherein said composition is obtained from the direct pressurization of a suspension of low-water-content polymeric nanocapsules preferably coated with chitosan, preferably with an active agent.

6. Composition according to claim 4, characterized in that the vehicle comprises a mixture of water and a polyol.

7. Composition according to claim 5, characterized in that the polyol is preferably propylene glycol or other polyols, derivatives and / or mixtures thereof.

8. Composition according to claim 6, characterized in that the polyol is preferably propylene glycol or other polyols, derivatives and / or mixtures thereof, or other water-containing protic solvents or mixtures thereof.

9. Composition, according to any one of claims 4 to 7, characterized in that it optionally comprises a surfactant and / or foaming agent, subsequently added to its external phase in isolation or in combination and / or with other agents, mainly antioxidants, stabilizers, chelating agents.

10. Composition, according to any one of claims 4 to 7, characterized in that it optionally comprises a liquid wax or a solid wax or mixtures thereof.

11. Composition, according to claim 9, characterized in that the liquid wax comprises one or more free fatty acids, primarily oleic acid, linoleic acid, palmitoleic acid, others, or a mixture of any two or more of these.

12. Composition, according to claim 9, Petition 870250046947, dated 05 / 06 / 2025, page 7 / 10 4 / 5, characterized in that the solid wax comprises mainly a fatty acid, a fatty alcohol, a microcrystalline wax, a petroleum wax, a polyethylene wax, a beeswax, castor wax, a tallow, a wool wax and a mixture of any two or more of these or others; and also a solid wax selected from the group composed of stearic acid, cetyl alcohol, behenyl alcohol, stearyl alcohol, cetostearyl alcohol and a mixture of two or more of these or others.

13. Composition, according to any one of claims 1 to 11, characterized in that it is provided in a sterile and sealed form, comprising at least one container in the form of a suspension, emulsion, powder, or lyophilized product, and preferably provided in a package, preferably with a cap, open or punctureable, and substantially a bag of liquid diluent or other, preferably in a traditional aerosol package, preferably with continuous spray technology such as Bag-on-Valve, Bag-in-Can, Bag-in-Can, and piston technology.

14. Use of the composition, as defined in any one of claims 4 to 12, characterized by being for the delivery of nanoparticulate drugs administered by aerosol therapy (APT) in patients who require locoregional treatment of diseases in poorly vascularized tissues such as hollow organs or body cavities or others.

15. Use, according to claim 13, characterized by being for the delivery of at least one nanoencapsulated chemotherapeutic substance, such as antineoplastics and others, mainly in chitosan-coated (mucoadhesive) polymeric nanocapsules.

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