Zero-blood-permeation Pickering emulsion entrapment system and application thereof

Abstract

The invention discloses a zero-blood-permeation Pickering emulsion entrapment system and application thereof.The zero-blood-permeation Pickering emulsion entrapment system is prepared by the steps that spirulina protein isolate and chitosan are dissolved in deionized water respectively, and a spirulina protein isolate solution and a chitosan solution are prepared; the preparation method comprises the following steps: mixing and stirring a spirulina protein isolate solution and a chitosan solution to prepare a spirulina protein isolate-chitosan composite nanoparticle dispersion liquid; and adding an oil phase containing an active matter into the spirulina isolated protein-chitosan composite nanoparticle dispersion liquid, and homogenizing to prepare the stable Pickering emulsion of the spirulina isolated protein-chitosan composite nanoparticles. The penetration enhancing system is used for skin drug delivery, can accurately deliver the drug into the epidermis or corium layer, does not cross the skin barrier to enter blood circulation, and is an optimal drug delivery system for treating diseases in the skin or modifying the skin structure.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines and cosmetics, and in particular relates to a Pickering emulsion encapsulation system with zero blood penetration and application thereof. Background Art

[0002] As the largest organ in the human body, the skin plays an important role in protecting the body from external damage, but it is also a major obstacle to drug absorption. The dense structure of the stratum corneum greatly limits the penetration of drug ingredients, affecting the efficiency of topical drug delivery. In order to overcome this challenge, it is particularly important to encapsulate bioactive ingredients in a carrier system, which can not only improve the delivery efficiency of the drug, but also enhance its stability and reduce potential side effects. Among the many carrier systems, emulsions have become the preferred choice for topical drug delivery due to their adjustable rheological properties, high loading capacity and easy preparation.

[0003] However, traditional emulsions usually rely on surfactants for stabilization, which may cause skin irritation and bring about environmental pollution problems, limiting their application in medicines and cosmetics.

[0004] Therefore, developing an effective, biosafe, and low-risk method to overcome the skin barrier is of great significance for pharmaceuticals, cosmetics, and special medical foods. Summary of the invention

[0005] The purpose of this section is to summarize some aspects of embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the specification abstract and the invention title of this application to avoid blurring the purpose of this section, the specification abstract and the invention title, and such simplifications or omissions cannot be used to limit the scope of the present invention.

[0006] In view of the above problems and / or the problems existing in the prior art, the present invention is proposed.

[0007] Therefore, the purpose of the present invention is to overcome the deficiencies in the prior art, solve the problem that active ingredients are difficult to cross the skin barrier, and provide a method for preparing a Pickering emulsion encapsulation system that is stabilized by Spirulina protein isolate-chitosan composite nanoparticles and achieves high skin retention of active substances while having zero blood penetration.

[0008] In order to solve the above technical problems, the present invention provides the following technical solution: a method for preparing a Pickering emulsion stabilized by spirulina protein isolate-chitosan composite nanoparticles, comprising:

[0009] Dissolving spirulina protein isolate (SPI) and chitosan (CS) in deionized water to prepare spirulina protein isolate solution and chitosan solution respectively;

[0010] The spirulina protein isolate solution and the chitosan solution are mixed and stirred to prepare a spirulina protein isolate-chitosan composite nanoparticle dispersion;

[0011] Bisabolol (ABS) is mixed with the oil phase and stirred, and then added into the dispersion of spirulina protein isolate-chitosan composite nanoparticles, and the stabilized Pickering emulsion of spirulina protein isolate-chitosan composite nanoparticles is prepared by homogenization or ultrasound.

[0012] As a preferred embodiment of the preparation method of the present invention, the concentration of the spirulina protein isolate-chitosan composite nanoparticle dispersion is 1-5wt% and the concentration of the chitosan solution is 0.2-4wt%.

[0013] As a preferred embodiment of the preparation method of the present invention, the spirulina protein isolate solution and the chitosan solution are mixed, wherein the mass ratio of the spirulina protein isolate solution to the chitosan solution is 1:0.2 to 1:3.

[0014] As a preferred solution of the preparation method of the present invention, the oil phase comprises sunflower oil, olive oil, caprylic and capric triglyceride, and the volume fraction of the oil phase of the Pickering emulsion is 25% to 85%.

[0015] As a preferred embodiment of the preparation method of the present invention, the homogenization time is 1 to 10 minutes, and the homogenization speed is 15000 to 18000 rpm.

[0016] As a preferred embodiment of the preparation method of the present invention, the Pickering emulsion has a particle size of 5-15 μm and a subcutaneous blood permeability of 0.

[0017] Another object of the present invention is to overcome the deficiencies in the prior art and provide a Pickering emulsion encapsulation system with zero blood penetration for use in the preparation of drugs or cosmetics with local delivery efficacy.

[0018] Beneficial effects of the present invention:

[0019] (1) The present invention proposes a Pickering emulsion encapsulation system that is stable for SPI-CS composite nanoparticles. It is found for the first time that the emulsion carrier of the present invention achieves zero skin permeability while maintaining a high skin retention rate, thereby avoiding the risk of active substances penetrating into the systemic circulation and facilitating local administration, which is difficult to achieve with other Pickering emulsion encapsulation systems. The encapsulation system of the present invention improves biosafety and shows good application prospects in the fields of cosmetics and medicine.

[0020] (2) The Pickering emulsion stabilized by the SPI-CS composite nanoparticles of the present invention has high stability and encapsulation efficiency, and no demulsification occurs during the 1-month storage at room temperature. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative labor. Among them:

[0022] Figure 1 These are optical microscope and appearance pictures of the Pickering emulsion in Example 1 of the present invention when it is freshly prepared and 30 days later at room temperature.

[0023] Figure 2 These are laser confocal images of bisabolol penetrating into pig skin in Example 6, Comparative Example 4 and Comparative Example 6 of the present invention, wherein a) is a bright field image, b) is a Nile red color channel image, and c) is an overlay image. DETAILED DESCRIPTION

[0024] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0025] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein, and those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0026] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The term "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive with other embodiments.

[0027] Unless otherwise specified, the materials and reagents used in this example were obtained from commercial sources.

[0028] Encapsulation efficiency and stability experiments of Pickering emulsion stabilized by SPI-CS composite nanoparticles:

[0029] The prepared SPI-CS composite nanoparticle dispersion and SPI solution were mixed with the oil phase and then homogenized to prepare a Pickering emulsion; the prepared Pickering emulsion was placed at room temperature, and its appearance was regularly observed and optical microscope pictures were taken.

[0030] The encapsulation efficiency (EE) was determined by the n-hexane extraction method: 1 mL of the above emulsion and 1 mL of n-hexane were mixed in a sealed centrifuge tube, shaken, and the supernatant was extracted overnight. The ABS content was measured using HPLC (Arc, Waters, USA) with a reverse phase C18 column (Cosmosil5C18-AR-Ⅱ packed column, 150 mm×4.6 mm, 5 μm). Acetonitrile and water were used as the mobile phase in a volume ratio of 78:22, and the flow rate of the mobile phase was 1 mL / min. The absorbance was detected at a wavelength of 210 nm.

[0031] EE is calculated by the following equation:

[0032] EE (%) = (amount of active substance encapsulated in the emulsion) / (total amount of active substance added) x 100%.

[0033] In vitro skin retention and permeation studies:

[0034] Franz diffusion cell was used to measure the skin retention of active ingredients before and after sample application. There was fresh pig skin between the diffusion cell and the supply cell, and the diffusion cell area was 3.14 cm 2 .

[0035] After the in vitro permeation test, the skin was removed and the content of active substance in the receiving solution was determined by HPLC. The residual emulsion in the supply pool was collected, extracted with anhydrous ethanol, and the residual amount on the skin surface was determined by HPLC.

[0036] Subsequently, the stratum corneum was peeled off with tape, and the collected tape was soaked in ethanol, ultrasonically extracted, and the content in the stratum corneum was determined by HPLC; the remaining skin surface after 20 tape peelings was cut into small pieces, mixed with ethanol, ultrasonically extracted, and the content in the remaining skin surface (viable epidermis and dermis) was determined by HPLC.

[0037] Example 1

[0038] SPI and CS were dissolved in deionized water to prepare SPI solution and CS solution respectively. The SPI solution was added into the CS solution, and the mixture was stirred for 60 minutes to obtain a dispersion of Spirulina protein isolate-chitosan composite nanoparticles, wherein the concentration of SPI was 1.0wt% and the concentration of CS was 0.4wt%.

[0039] Afterwards, GTCC was added to the dispersion with an oil-water volume ratio of 1:1, and homogenized at 15000 rpm for 2 min to prepare a Pickering emulsion.

[0040] Optical microscopy and appearance of Pickering emulsions freshly prepared and 30 days after preparation at room temperature are shown in Figure 1 .

[0041] Example 2

[0042] SPI and CS were dissolved in deionized water to prepare SPI solution and CS solution respectively. The SPI solution was added into the CS solution, and the mixture was stirred for 60 minutes to obtain a dispersion of Spirulina protein isolate-chitosan composite nanoparticles, wherein the concentration of SPI was 1.0wt% and the concentration of CS was 0.8wt%.

[0043] Afterwards, GTCC was added to the dispersion with an oil-water volume ratio of 1:1, and homogenized at 15000 rpm for 2 min to prepare a Pickering emulsion.

[0044] Example 3

[0045] SPI and CS were dissolved in deionized water to prepare SPI solution and CS solution respectively. The SPI solution was added into the CS solution, and the mixture was stirred for 60 minutes to obtain a dispersion of Spirulina protein isolate-chitosan composite nanoparticles, wherein the concentration of SPI was 1.0wt% and the concentration of CS was 0.2wt%.

[0046] Afterwards, GTCC was added to the dispersion with an oil-water volume ratio of 1:1, and homogenized at 15000 rpm for 2 min to prepare a Pickering emulsion.

[0047] Example 4

[0048] SPI and CS were dissolved in deionized water to prepare SPI solution and CS solution respectively. The SPI solution was added into the CS solution, and the mixture was stirred for 60 minutes to obtain a dispersion of Spirulina protein isolate-chitosan composite nanoparticles, wherein the concentration of SPI was 2.0wt% and the concentration of CS was 2.0wt%.

[0049] Afterwards, GTCC was added to the dispersion with an oil-water volume ratio of 1:1, and the Pickering emulsion was prepared by homogenization at 16000 rpm for 2 min.

[0050] Example 5

[0051] SPI and CS were dissolved in deionized water to prepare SPI solution and CS solution respectively. The SPI solution was added into the CS solution, and the mixture was stirred for 60 minutes to obtain a dispersion of Spirulina protein isolate-chitosan composite nanoparticles, wherein the concentration of SPI was 2.0wt% and the concentration of CS was 2.0wt%.

[0052] Afterwards, GTCC was added to the dispersion with an oil-water volume ratio of 3:1, and the Pickering emulsion was prepared by homogenization at 16000 rpm for 2 min.

[0053] Comparative Example 1

[0054] SPI was dissolved in deionized water to prepare an SPI solution, wherein the concentration of SPI was 1.0 wt %. Then, GTCC was added to the SPI solution, wherein the oil-water volume ratio was 1:1, and homogenized at 15000 rpm for 2 min to prepare an SPI-stabilized Pickering emulsion.

[0055] Comparative Example 2

[0056] CS was dissolved in deionized water to prepare a CS solution, wherein the concentration of CS was 1.0 wt %. Then, GTCC was added to the CS solution, wherein the oil-water volume ratio was 1:1, and homogenized at 15000 rpm for 2 min to prepare a CS-stabilized Pickering emulsion.

[0057] Comparative Example 3

[0058] SPI and CS were dissolved in deionized water to prepare SPI solution and CS solution respectively. The SPI solution was added into the CS solution, and the mixture was stirred for 60 minutes to obtain a dispersion of Spirulina protein isolate-chitosan composite nanoparticles, wherein the concentration of SPI was 1.0wt% and the concentration of CS was 0.1wt%.

[0059] Afterwards, GTCC was added to the dispersion with an oil-water volume ratio of 1:1, and homogenized at 15000 rpm for 2 min to prepare a Pickering emulsion.

[0060] Table 1 Changes in droplet size of emulsions stabilized by SPI, CS and SPI-CS before and after storage at room temperature for 30 days

[0061]

[0062]

[0063] As shown in Table 1, the particle size of the emulsions stabilized by SPI (Comparative Example 1) and CS (Comparative Example 2) alone is nearly 5 times larger than that of the emulsions stabilized by the SPI-CS composite nanoparticles, and both exhibit some instability after storage for 30 days.

[0064] When the proportion of CS in the SPI-CS composite particles is relatively low (Comparative Example 3), the stable emulsion is also unstable. After 30 days, droplets coalesce and gradually change from spherical to rod-shaped. When the content of CS is greater than or equal to 0.2wt%, the emulsion compounded with SPI has good storage stability. After being stored at room temperature for 30 days, no demulsification occurs, and the particle size is small.

[0065] Example 6

[0066] SPI and CS were dissolved in deionized water to prepare SPI solution and CS solution respectively. The SPI solution was added into the CS solution, and the mixture was stirred for 60 minutes to obtain a dispersion of Spirulina protein isolate-chitosan composite nanoparticles, wherein the concentration of SPI was 1.0wt% and the concentration of CS was 0.4wt%.

[0067] Afterwards, GTCC containing bisabolol (bisabolol concentration was 200 mg / mL) was added to the dispersion with an oil-water volume ratio of 1:1, and homogenized at 15000 rpm for 5 min to prepare a Pickering emulsion.

[0068] Using pig skin as an in vitro model, the prepared Pickering emulsion was applied to the top of the diffusion cell to detect the amount of bisabolol penetrating and passing through the skin.

[0069] Example 7

[0070] SPI and CS were dissolved in deionized water to prepare SPI solution and CS solution, and the SPI solution was added to the CS solution, and the mixture was stirred for 60 minutes to obtain a dispersion of Spirulina protein isolate-chitosan composite nanoparticles, wherein the concentration of SPI was 1.5wt% and the concentration of CS was 0.6wt%. After that, GTCC containing bisabolol (bisabolol concentration was 200mg / mL) was added to the dispersion, wherein the oil-water volume ratio was 1:1, and the mixture was homogenized at 15000rpm for 10 minutes to prepare a Pickering emulsion. Using pig skin as an in vitro model, the prepared Pickering emulsion was applied to the top of the diffusion cell to detect the amount of bisabolol penetrating and passing through the skin.

[0071] Example 8

[0072] SPI and CS were dissolved in deionized water to prepare SPI solution and CS solution, and the SPI solution was added to the CS solution, and the mixture was stirred for 60 minutes to obtain a dispersion of Spirulina protein isolate-chitosan composite nanoparticles, wherein the concentration of SPI was 2.0wt% and the concentration of CS was 0.8wt%. After that, GTCC containing bisabolol (bisabolol concentration was 200mg / mL) was added to the dispersion, wherein the oil-water volume ratio was 1:1, and the mixture was homogenized at 15000rpm for 10 minutes to prepare a Pickering emulsion. Using pig skin as an in vitro model, the prepared Pickering emulsion was applied to the top of the diffusion cell to detect the amount of bisabolol penetrating and passing through the skin.

[0073] Example 9

[0074] SPI and CS were dissolved in deionized water to prepare SPI solution and CS solution, and the SPI solution was added to the CS solution, and the mixture was stirred for 60 minutes to obtain a dispersion of Spirulina protein isolate-chitosan composite nanoparticles, wherein the concentration of SPI was 1.5wt% and the concentration of CS was 0.6wt%. After that, GTCC containing bisabolol (bisabolol concentration was 200 mg / mL) was added to the dispersion, wherein the oil-water volume ratio was 3:1, and the mixture was homogenized at 15000 rpm for 10 minutes to prepare a Pickering emulsion.

[0075] Using pig skin as an in vitro model, the prepared Pickering emulsion was applied to the top of the diffusion cell to detect the amount of bisabolol penetrating and passing through the skin.

[0076] Example 10

[0077] SPI and CS were dissolved in deionized water to prepare SPI solution and CS solution respectively. The SPI solution was added into the CS solution, and the mixture was stirred for 60 minutes to obtain a dispersion of Spirulina protein isolate-chitosan composite nanoparticles, wherein the concentration of SPI was 1.5wt% and the concentration of CS was 0.6wt%.

[0078] Afterwards, GTCC containing bisabolol (bisabolol concentration was 200 mg / mL) was added to the dispersion, wherein the oil-water volume ratio was 85:15, and homogenization was performed at 15000 rpm for 10 min to prepare a Pickering emulsion.

[0079] Using pig skin as an in vitro model, the prepared Pickering emulsion was applied to the top of the diffusion cell to detect the amount of bisabolol penetrating and passing through the skin.

[0080] Comparative Example 4

[0081] SPI and CS were dissolved in deionized water to prepare SPI solution and CS solution, and the SPI solution was added to the CS solution, and the mixture was stirred for 60 minutes to obtain a dispersion of Spirulina protein isolate-chitosan composite nanoparticles, wherein the concentration of SPI was 1.0wt% and the concentration of CS was 0.1wt%. After that, GTCC containing bisabolol (bisabolol concentration was 200 mg / mL) was added to the dispersion, wherein the oil-water volume ratio was 1:1, and the mixture was homogenized at 15000 rpm for 5 minutes to prepare a Pickering emulsion.

[0082] Using pig skin as an in vitro model, the prepared Pickering emulsion was applied to the top of the diffusion cell to detect the amount of bisabolol penetrating and passing through the skin.

[0083] Comparative Example 5

[0084] SPI was dissolved in deionized water to prepare an SPI solution, wherein the concentration of SPI was 1.0 wt %. Then, GTCC containing bisabolol (bisabolol concentration was 200 mg / mL) was added to the dispersion, wherein the oil-water volume ratio was 1:1, and homogenized at 15000 rpm for 5 min to prepare a Pickering emulsion.

[0085] Using pig skin as an in vitro model, the prepared Pickering emulsion was applied to the top of the diffusion cell to detect the amount of bisabolol penetrating and passing through the skin.

[0086] Comparative Example 6

[0087] Using pig skin as an in vitro model, GTCC containing bisabolol (bisabolol concentration of 200 mg / mL) was applied to the top of the diffusion cell to detect the amount of bisabolol that penetrated the skin and passed through the skin.

[0088] Comparative Example 7

[0089] CS was dissolved in deionized water to prepare a CS solution, wherein the concentration of CS was 1.0 wt %. Then, GTCC containing bisabolol (bisabolol concentration was 200 mg / mL) was added to the CS solution, wherein the oil-water volume ratio was 1:1, and homogenization was performed at 15000 rpm for 5 min to prepare a CS-stabilized Pickering emulsion, which demulsified and stratified within 24 h.

[0090] Comparative Example 8

[0091] Using pig skin as an in vitro model, the commercially available bisabolol antipruritic lotion was The amount of bisabolol penetrating and passing through the skin was measured by applying it to the top of the diffusion cell.

[0092] Table 2 Skin retention and permeation of emulsions stabilized by SPI, CS and SPI-CS

[0093]

[0094] As shown in Table 2, active substances were detected in the receiving pool, that is, the active substances failed to penetrate the skin and enter the receiving solution. Analysis of the skin retention found that the skin retention detected in Example 6 was 1.6 times that of Example 4, 1.9 times that of Example 5, and 3.5 times that of Example 6. It shows that the system has a significant effect on promoting skin retention of active substances, and there is no risk of entering the blood circulation. When the SPI concentration is increased (Example 7 and Example 8), the skin retention is 3.6 times and 3.4 times that of Example 6, respectively, indicating that increasing the SPI concentration to a certain extent can increase the skin retention, but as the concentration continues to increase, the skin retention does not change significantly. When the oil phase volume fraction is increased, the skin straight amount of the Pickering emulsion increases, and the maximum is 4.2 times that of Example 6. It shows that the system has a significant effect on promoting skin retention of active substances, and there is no risk of entering the blood circulation. At the same time, compared with the red bisabolol cream (Comparative Example 8) of the product, it is found that the skin retention in Example 6 is about 2.5 times. Most notably, the large amount of permeation in Comparative Example 8, which is more than 3 times its skin retention, indicates that most of the bisabolol crosses the skin barrier and enters the blood circulation, making it not an ideal emulsion for topical delivery.

[0095] The transdermal delivery efficiency of Pickering emulsion was determined using Franz diffusion cell, as shown in Table 2 and Figure 2 As shown, after being treated with the Pickering emulsion, the amount of active substance detected in the active epidermis and dermis is 1.6 to 4.2 times that of the comparative example, indicating that the system has a significant penetration-promoting ability for the active substance. At the same time, no active substance was detected in the receiving solution of all samples, indicating that the Pickering emulsion prepared by the present invention has no risk of penetrating into the systemic circulation and is conducive to local administration.

[0096] Comparative Example 9

[0097] The corresponding skin retention rates and permeation rates of several Pickering emulsions reported so far are shown in Table 3.

[0098] Table 3

[0099]

[0100] [1]Enhancing trans-resveratrol topical delivery and photostability through entrapment in chitosan / gum Arabic Pickering emulsions, International Journal of Biological Macromolecules, 147 (2020) 150–159.

[0101] [2] Pickering emulsions stabilized with chitosan / collagen peptidesnanoparticles as green topical delivery vehicles for cannabidiol (CBD), Colloids and Surfaces A: Physicochemical and Engineering Aspects, 631 (2021) 127677.

[0102] Compared with the skin retention rate and permeability of other Pickering emulsion systems in Table 3, the Pickering emulsion carrier in the present invention not only maintains a high skin retention rate, but also achieves zero skin permeability, avoiding the risk of active substances penetrating into the systemic circulation, which is beneficial for local administration. On the one hand, this may be related to the thickness of the emulsion interface film, which can delay the release of active substances and reduce the osmotic pressure of active substance delivery; on the other hand, it may be related to the molecular weight and helical structure of SPI, which can adsorb active substances and reduce the concentration of free active substances, ultimately preventing the particle / active substance complex from crossing the skin tissue and entering the blood.

[0103] The present invention proposes a Pickering emulsion encapsulation system for SPI-CS composite nanoparticles, and for the first time finds that the emulsion carrier of the present invention achieves zero skin permeability while maintaining a relatively high skin retention rate, thereby avoiding the risk of active substances penetrating into the systemic circulation and facilitating local administration, which is difficult to achieve with other Pickering emulsion encapsulation systems; the encapsulation system of the present invention improves biosafety and shows good application prospects in the fields of cosmetics and medicine.

[0104] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the present invention.

Claims

1. A Pickering emulsion encapsulation system with zero blood penetration, characterized in that: include, Dissolving spirulina protein isolate and chitosan in deionized water respectively to prepare spirulina protein isolate solution and chitosan solution; The spirulina protein isolate solution and the chitosan solution are mixed, and the spirulina protein isolate-chitosan composite nanoparticle dispersion is prepared after ultrasonic treatment; The oil phase is added into the dispersion of Spirulina protein isolate-chitosan composite nanoparticles, and the Spirulina protein isolate-chitosan composite nanoparticles stable Pickering emulsion encapsulation system is prepared by homogenization or ultrasonication.

2. The encapsulation system according to claim 1, characterized in that: The spirulina protein isolate-chitosan composite nanoparticle dispersion liquid comprises: a spirulina protein isolate solution having a concentration of 1-5 wt % and a chitosan solution having a concentration of 0.2-4 wt %.

3. The encapsulation system according to claim 1 or 2, characterized in that: The spirulina protein isolate solution and the chitosan solution are mixed, wherein the mass ratio of the spirulina protein isolate solution to the chitosan solution is 1:0.2 to 1:

3.

4. The packaging system according to claim 1, characterized in that: The oil phase comprises sunflower oil, olive oil and caprylic / capric triglyceride.

5. The encapsulation system according to claim 1 or 4, characterized in that: The volume fraction of the oil phase of the Pickering emulsion is 25% to 85%.

6. The encapsulation system according to claim 1, characterized in that: The homogenization time is 1 to 10 minutes, and the homogenization speed is 15000 to 18000 rpm.

7. The encapsulation system according to any one of claims 1, 2, 4 or 6, characterized in that: The preparation method further comprises: The active substance is added into the oil phase, and the mixture is homogenized with the spirulina protein isolate-chitosan composite nanoparticle dispersion to prepare a Pickering emulsion stabilized by the spirulina protein isolate-chitosan composite nanoparticle dispersion containing the active substance.

8. The packaging system according to claim 7, characterized in that: The actives include curcumin, resveratrol and bisabolol.

9. The Pickering emulsion encapsulation system with zero blood penetration as claimed in claim 1 or 8, characterized in that: The particle size of the emulsion of the encapsulation system is 5-15 μm, and the subcutaneous blood penetration is 0.

10. Use of the Pickering emulsion encapsulation system with zero blood penetration according to any one of claims 1 to 9 in the preparation of drugs or cosmetics with local delivery efficacy.

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