Polymeric membrane of pva, pluronic f127 and glycerol functionalized with graphene encapsulated by pluronic f127 micelles for biomedical applications

Description

/ 6 Polymeric membrane of PVA, Pluronic F127 and glycerol functionalized with graphene encapsulated by Pluronic F127 micelles for biomedical applications. Field of invention

[01] The present invention belongs to the field of biomaterials, more specifically to polymeric formulations for applications in wound dressings and controlled drug delivery systems. Fundamentals of the invention

[02] The main criterion for the selection of biomaterials is their acceptance by the human body. A biomaterial is any substance, natural or synthetic, that interacts with cells, tissues, or organs without inducing adverse reactions (BANORIYA; PUROHIT; DWIVEDI, 2017). Its performance depends on its structural and physicochemical properties, as well as biocompatibility (JAGUR-GRODZINSKI, 1999). Polymeric materials for biomedical applications are highly versatile, exhibiting diverse properties such as: functional groups, hydrophobic / hydrophilic character, wettability and surface energy, flexibility, and roughness (JURAK et al., 2021).

[03] Of the various polymer options, the Pluronic F127 triblock copolymer (PF127) and the Polyvinyl Alcohol (PVA) homopolymer possess several desirable properties for developing biomaterials. PF127 stands out for the presence of hydrophobic and hydrophilic groups, thermal responsiveness, and the ability to form nanostructures, such as micelles (SAHU et al., 2011). PVA, on the other hand, offers the biomaterial mechanical stability, adhesive nature, and hydrophilicity (BAKER et al., 2012). These characteristics allow the creation of versatile structures, such as hydrogels, micelles, and, especially, polymeric membranes.

[04] Membranes function as barriers that allow selective mass transport, gaining increasing versatility as they are synthesized from polymeric materials. The multiple characteristics of these membranes have aroused great scientific interest, driving research in various areas, especially in the sector Petition 870250069281, dated 05 / 08 / 2025, page 4 / 12 / 6 biomedical (RADU; VOICU; THAKUR, 2023), where PF127 and PVA offer several advantages regarding their application.

[05] PVA-based polymeric membranes stand out for their biocompatibility, high chemical and mechanical resistance, bioadhesiveness, hydrophilicity, and economic viability (RICCIO et al., 2022). These properties allow applications such as contact lenses, membranes for hemodialysis, and hydrophilic coatings for neurological regeneration (BAKER et al., 2012). However, challenges persist, such as high resistance to elongation and difficulty in pore formation, which limit adaptability to different biological systems (JURAK et al., 2021).

[06] PF127 contributes to the formation of polymeric membranes, offering thermal responsiveness, encapsulation capacity, and micellar structure formation (ATTWOOD; COLLETT; TAIT, 1985). Furthermore, it has the ability to interact with cell membranes, primarily stimulating transforming growth factor-βΐ (TGF-β1) and vascular endothelial growth factor (VEGF), which promote wound healing (LI et al., 2023). PF127 also regulates pore formation on the membrane surface, acting as a pore-forming agent, promoting stability and uniformity, and improving cell adhesion in various biological systems (MCHUGH, 2005). However, the weak mechanical properties of this polymer limit its use as a membrane (AKASH; REHMAN, 2015).

[07] The use of PVA and PF127 in the synthesis of polymeric membranes is quite promising. Dmitrenko and colleagues showed that introducing PF127 into PVA membranes improved cargo transport properties, as well as cavity formation and hydrophilization (DMITRENKO et al., 2022). Another study indicates that electrospun polymeric membranes of PF127 and PVA crosslinked with citric acid have potential use in drug delivery (S. ROSSIN et al., 2025). However, when consulting the INPI database, it was not possible to find any patent registration on the use of both materials for the formation of polymeric membranes.

[08] The use of other components can provide important additional improvements for the desired applications. Glycerol as an additive in polymeric membranes is Petition 870250069281, dated 05 / 08 / 2025, page 5 / 12 / 6 widely documented in the literature (COBOS; FERNÁNDEZ; FERNÁNDEZ, 2018; ZENG et al., 2022). PVA-based membranes with glycerol have shown improvements in flexibility, thermal stability, tensile strength, and toughness, without compromising the material composition (JAMALI; SHAIKH; CHANDIO, 2023). Sweah used glycerin, the commercial name for glycerol (BEATRIZ; ARAÚJO; LIMA, 2011), to improve tensile strength, decrease the modulus of elasticity, and increase interfacial adhesion between PVA and PF127 in a polymeric membrane for controlled drug release (SWEAH, 2020).

[09] In order to enhance the controlled release of drugs, graphene shows promise in micellar PF127 systems. Incorporation of graphene into PF127 has shown efficiency in encapsulation and loading of doxorubicin with pH-responsive behavior (HU et al., 2012). In contrast, electrospun graphene membranes with cross-linked PVA indicated sustained release of chlorhexidine for up to 500 h (GULINO et al., 2022). Even with promising results, the combination of PVA and PF127 with encapsulated graphene has not yet been properly investigated.

[0010] The invention proposes an innovative polymeric film that combines PVA, Pluronic F127 and glycerol with graphene encapsulated by Pluronic F127 micelles. This approach improves graphene dispersion, giving the material better mechanical strength, adhesion to the skin in the presence of moisture, and the possibility of incorporating drugs.

[0011] The material is composed of a PVA matrix combined with glycerol as a plasticizer, ensuring flexibility and adjustability of mechanical rigidity. Pluronic F127 acts in the stabilization of graphene through the formation of micelles, promoting homogeneous dispersion and increasing interaction with hydrophobic drugs. The film can be prepared by solvent casting from a casting solution and dried under controlled conditions. Problems existing in the state of the art

[0012] Some problems present in the state of the art of polymeric membranes stand out: (1) PVA-based membranes have high tensile strength and a high Young's modulus; (2) PVA-based membranes have a dense morphology, with an absence of porosity; (3) A large part of PF127-based materials have Petition 870250069281, dated 05 / 08 / 2025, page 6 / 12 / 6 insufficient mechanical properties; (4) The use of other components may help improve mechanical properties and controlled drug release Advantages of the invention

[0013] The advantages of the invention are highlighted: (1) Greater tensile strength and reduction of Young's modulus; (2) Formation of pores in the polymeric membrane; (3) Adhesiveness and hydrophilicity; (4) Graphene encapsulated in micellar structures to act as a drug nanocarrier. Brief description of the drawings Figure 1. The white arrows on the topographic map obtained by AFM (A) indicate the stability of the PF127 micelles with encapsulated graphene. The Young's modulus maps (B) confirm the presence of graphene inside the micelles. Figure 2. MPG-9010 (A), MPG-8020 (B) and MPG-7030 (C) polymeric membranes. Figure 3. SEM images of the MPG-8020 polymeric membrane showing the large presence of pores on the surface (AB) with an average diameter ± standard deviation of 1.78 ± 0.57 μm. EDS © data show the chemical composition of the membrane consisting of carbon, hydrogen, and oxygen. The presence of gold indicates the material's metallization process. Figure 4. 2D (A) and 3D (B) topographic maps of the MPG-8020 polymer membrane showing the pore on its surface. Figure 5. Tensile test of MPG-9010, MPG-8020 and MPG7030 polymer membranes showing the influence of proportions on tensile deformation. Figure 6. Adhesion of the MPG-8020 polymeric membrane to the skin, viewed from different angles: lateral (A) and superior (B). Description of the invention

[0014] The following polymers were used: PF127 (Sigma Aldrich), PVA (ACS Cientifica), Glycerol (ISOFARA), and an 8B Faber-Castell pencil. A 3% (w / v) solution of Petition 870250069281, dated 05 / 08 / 2025, page 7 / 12 / 6 PVA with distilled water as solvent was prepared on a magnetic stirrer. In parallel, a second PF127 solution with 3% (w / v) distilled water was similarly prepared. Subsequently, 1 gram of graphite from an 8B pencil was added to the PF127 solution and placed in a probe sonicator for 30 min at 80 W, obtaining graphene in the polymer solution. The PF127 solution was filtered using filter paper with a pore size <20 μm. 0.6 mL of glycerol was added to the PF127 solution during magnetic stirring, obtaining a PF127 solution with encapsulated graphene and glycerol.

[0015] The solvent casting method by evaporation was used in the preparation of polymeric membranes due to its operational simplicity, low cost, and ability to form homogeneous films with satisfactory mechanical properties. This technique allows for greater versatility in the formulation of MPs and offers better control over processing conditions compared to methods such as salt leaching and spin coating (BORBOLLA-JIMÉNEZ et al., 2023).

[0016] For processing the polymeric membrane, a 100 mL solution was prepared from the previously prepared polymeric solutions. Initially, 90 mL of the PVA solution were added to a beaker under constant magnetic stirring. Subsequently, 10 mL of the PF127 solution with graphene and glycerol were added to the beaker, bringing the volume to 100 mL. After a period of 10 minutes, the casting solution was ready.

[0017] In an 8 cm diameter Petri dish, 20 mL of the casting solution were carefully poured. The dish was then placed in an oven at 100 °C for 3 hours. Finally, the dish was removed from the oven and left at room temperature overnight to facilitate membrane removal.

[0018] The sample obtained from 90 mL of PVA solution and 10 mL of PF127 solution with graphene and glycerol was designated as MPG-9010. Additionally, MPG-8020 and MPG-7030 membranes were obtained following the same processing. Examples of embodiments of the invention Petition 870250069281, dated 05 / 08 / 2025, page 8 / 12 / 6

[0019] The material is composed of a PVA matrix combined with glycerol as a plasticizer, ensuring flexibility and adjustability of mechanical rigidity. Pluronic F127 acts in the stabilization of graphene through the formation of micelles, promoting homogeneous dispersion and increasing interaction with hydrophobic drugs.

[0020] The MPG-9010, MPG-8020, and MPG-7030 membrane group showed versatility in terms of their physical and structural properties. The combination of AFM and SEM / EDS techniques shows that MPG-8020 membranes exhibit the greatest pore formation.

[0021] Adjusting mechanical and structural properties is essential for the effectiveness of biomaterials, influencing cellular interaction, adhesion, and adaptability. The presented invention allows obtaining a wide range of properties from the same precursors by varying their concentrations. This enables applications such as biomedical dressings for wound healing and controlled drug release, therapeutic platforms for prolonged wound treatment, scaffolds for tissue engineering, and biocompatible coatings in medical devices, reducing rejection and improving integration with biological tissues. Petition 870250069281, dated 05 / 08 / 2025, page 9 / 12

Claims

1 / 2 CLAIMS 1. Polymeric membrane of PVA, Pluronic F127 and glycerol functionalized with graphene encapsulated by Pluronic F127 micelles for biomedical applications, characterized by being composed of polyvinyl alcohol (PVA), Pluronic F127 (PF127), glycerol and graphene encapsulated by Pluronic F127 micelles, obtained by solvent casting.

2. Polymeric membrane of PVA, Pluronic F127 and glycerol functionalized with graphene encapsulated by Pluronic F127 micelles for biomedical applications, according to claim 1, characterized by containing solutions of 3% (w / v) of PVA and 3% (w / v) of PF127 containing graphene and glycerol, with 0.6 mL of glycerol incorporated into the PF127 solution.

3. Polymeric membrane of PVA, Pluronic F127 and glycerol functionalized with graphene encapsulated by Pluronic F127 micelles for biomedical applications, according to claim 1, characterized by having variations in composition, with PVA solution volumes of 90 mL, 80 mL and 70 mL, and PF127 solution volumes containing graphene and glycerol of 10 mL, 20 mL and 30 mL, totaling 100 mL in the casting solution.

4. A polymeric membrane of PVA, Pluronic F127 and glycerol functionalized with graphene encapsulated by Pluronic F127 micelles for biomedical applications, according to claims 1, 2 and 3, characterized by 90 mL of PVA and 10 mL of PF127 with graphene and glycerol, is described as follows: MPG-9010.

5. Polymeric membrane of PVA, Pluronic F127 and glycerol functionalized with graphene encapsulated by Pluronic F127 micelles for biomedical applications, according to claims 1, 2 and Petition 870250069281, dated 05 / 08 / 2025, p. 10 / 12 2 / 2 3, characterized by 80 mL of PVA and 20 mL of PF127 with graphene and glycerol, to be described as follows: MPG-8020.

6. A polymeric membrane of PVA, Pluronic F127 and glycerol functionalized with graphene encapsulated by Pluronic F127 micelles for biomedical applications, according to claims 1, 2 and 3, characterized by 70 mL of PVA and 30 mL of PF127 with graphene and glycerol, is described as follows: MPG-7030.

7. Polymeric membrane of PVA, Pluronic F127 and glycerol functionalized with graphene encapsulated by Pluronic F127 micelles for biomedical applications, according to claims 1, 2 and 3, characterized by presenting different levels of flexibility, surface porosity control and adhesion in a humid environment, these properties being adjustable according to the concentration of the components. Petition 870250069281, dated 05 / 08 / 2025, page 11 / 12

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