CN117695378A - Drug carrying system and preparation method and application thereof - Google Patents
Drug carrying system and preparation method and application thereof Download PDFInfo
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Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The application belongs to the field of biological medicine, and the application discovers through the research that carrying VEGFC and VEGFA on the carrier as a medicine carrying system can promote diabetes wound repair, provides a medicine carrying system from this, contains carrier, VEGFA and VEGFC, wherein VEGFA and VEGFC load on the carrier as the medicine that promotes diabetes wound repair. Meanwhile, the influence of different drug dosage ratios on the morphology and the function of the new blood vessel and the lymphatic vessel is explored, and the VEGFC and VEGFA are found to promote the generation of the blood vessel and the lymphatic vessel and promote the regeneration of the vascular vessel and the wound healing of diabetics.
Description
Technical Field
The application belongs to the field of biological medicine, and in particular relates to a medicine carrying system and a preparation method and application thereof.
Background
Diabetes is a chronic metabolic disease, which is mainly characterized by an increase in blood glucose concentration. Diabetes can lead to complications of many tissues and organs, of which about one third of diabetics are exposed to skin lesions during the course of the onset of disease, facing serious problems of poor wound healing, chronic ulcers and even amputation. For example, diabetic skin disease is a collective term for the specific skin manifestations of diabetes, whose incidence is positively correlated with the duration and severity of diabetes, and almost all diabetics have related skin lesions, but are most commonly seen in elderly patients. Diabetic skin disease is a specific skin manifestation of diabetes, and the immunoregulatory dysfunction of diabetics and the rise of blood sugar level are beneficial to pathogen reproduction, and diabetic neuropathy causes skin to be easily damaged and not to be easily healed. The pathogenesis of the disease is not detailed, and probably the diabetes mellitus patient has glycoprotein deposited on the basal membrane of capillary vessels, so that the wall of the vessel is thickened and the tissue is anoxic, and the multi-factor pathological process mainly comprising the micro-vascular pathological changes is caused.
Diabetes is a systemic metabolic disease, so that diabetic skin diseases are various in appearance and can have a great influence on the quality of life of patients, and attention should be paid. Microbial infection of wound surface, impaired immune function, etc., are main causes of difficult healing of skin. In addition, peripheral vascular lesions caused by diabetes further exacerbate the inflammatory response of the skin, thereby affecting repair of skin lesions.
Blood vessels are channels for transporting nutrients and oxygen and play a vital role in the wound healing process. Studies have shown that endothelial dysfunction due to hyperglycemia leads to impaired angiogenesis and reduced vascularization, leading to delayed wound healing or dysfunction. Promoting wound surface blood vessel regeneration, improving local blood supply, and is key for treating diabetes wound surface.
At present, no related medicine for repairing the diabetic skin injury based on promoting the regeneration of micro-vessels exists.
Disclosure of Invention
Based on the above, an embodiment of the application provides a drug-carrying system, a preparation method and application thereof, and the drug-carrying system can be used as a healing drug for diabetic skin wounds.
In one aspect, the application provides a drug delivery system comprising a carrier, VEGFA and VEGFC, wherein VEGFA and VEGFC are carried on the carrier.
In one embodiment, the mass ratio of VEGFA to VEGFC is (0.8-1.2): 0.8-1.2.
In one embodiment, the mass ratio of VEGFA to VEGFC is 1 (0.8-1.2).
In one embodiment, the ratio of the mass to volume of the VEGFA to the carrier is (400-600) ng/1 ml, and the ratio of the mass to volume of the VEGFC to the carrier is (400-600) ng/1 ml.
In one embodiment, the carrier comprises a methacryloylated hydrogel.
In one embodiment, the methacryloylated hydrogel comprises one or more of a methacryloylated hyaluronic acid hydrogel, a methacryloylated chitosan hydrogel.
In one embodiment, the volume percent of methacrylic acid in the methacryloylated hydrogel is 14% to 16%.
The application also provides application of the drug delivery system in preparing a medicine for healing diabetic skin wounds.
In one embodiment, the medicament further comprises pharmaceutically acceptable excipients.
In one embodiment, the adjuvant is selected from one or more of a diluent, a binder, a disintegrant, a lubricant, and a wetting agent.
In one embodiment, the dosage form of the medicament is one or more of a tablet, a capsule, a granule, a pill, an injection and a sustained release preparation.
In another aspect, the present application provides a method of preparing a drug delivery system, comprising the steps of:
the vehicle was mixed with VEGFA and VEGFC to prepare a drug delivery system.
The application finds that the VEGFC and the VEGFA are loaded on a carrier to serve as a drug loading system, and can serve as a healing drug for diabetic skin wounds. Furthermore, the application discovers the influence of different drug dosage ratios on the morphology and the function of the new blood vessel and the lymphatic vessel, and discovers that VEGFC and VEGFA can promote the generation of the blood vessel and the lymphatic vessel of a diabetes patient, thereby playing roles in regenerating vessels and healing wounds.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present application and to more fully understand the present application and its advantageous effects, the following brief description will be given with reference to the accompanying drawings, which are required to be used in the description of the embodiments. It is obvious that the drawings in the following description are only some embodiments of the present application, and that other drawings may be obtained from these drawings without inventive effort to a person skilled in the art.
FIG. 1 is a normal mouse skin injury site healing process monitoring;
FIG. 2 is a monitoring of the healing process of skin lesions in diabetic mice;
fig. 3 is a graph of monitoring the healing process of skin lesions in diabetic mice coated with different drugs.
Detailed Description
The present application will be described in further detail with reference to embodiments and examples. It should be understood that these embodiments and examples are provided solely for the purpose of illustrating the application and are not intended to limit the scope of the application in order to provide a more thorough understanding of the present disclosure. It is also to be understood that this application may be embodied in many different forms and is not limited to the embodiments and examples described herein, but is capable of numerous changes or modifications without departing from the spirit of the application, as equivalent forms are intended to be within the scope of this application. Furthermore, in the following description, numerous specific details are set forth in order to provide a more thorough understanding of the present application, it being understood that the present application may be practiced without one or more of these details.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
Terminology
All documents mentioned in this application are incorporated by reference in this application as if each were individually incorporated by reference. Unless otherwise conflict with the purpose and/or technical solution of the present application, the present application relates to the cited documents which are incorporated by reference in their entirety for all purposes. When reference is made to a cited document in this application, the definitions of the relevant technical features, terms, nouns, phrases, etc. in the cited document are also incorporated by reference. Examples of the relevant technical features and preferred modes to be cited in the present application when the cited documents are referred to in the present application are incorporated by reference in the present application, but are not limited to being able to implement the present application. It should be understood that when a reference is made to the description herein, it is intended to control or adapt the present application in light of the description herein.
Unless otherwise indicated or contradicted, terms or phrases used herein have the following meanings:
the term "and/or," "and/or," as used herein, includes any one of two or more of the listed items in relation to each other, as well as any and all combinations of the listed items in relation to each other, including any two of the listed items in relation to each other, any more of the listed items in relation to each other, or all combinations of the listed items in relation to each other. It should be noted that, when at least three items are connected by a combination of at least two conjunctions selected from "and/or", "or/and", "and/or", it should be understood that, in this application, the technical solutions certainly include technical solutions that all use "logical and" connection, and also certainly include technical solutions that all use "logical or" connection. For example, "a and/or B" includes three parallel schemes A, B and a+b. For another example, the technical schemes of "a, and/or B, and/or C, and/or D" include any one of A, B, C, D (i.e., the technical scheme of "logical or" connection), and also include any and all combinations of A, B, C, D, i.e., any two or three of A, B, C, D, and also include four combinations of A, B, C, D (i.e., the technical scheme of "logical and" connection).
In this application, reference is made to a numerical interval (i.e., a numerical range), where the optional numerical distribution is considered continuous, and includes two numerical endpoints (i.e., a minimum value and a maximum value) of the numerical range, and each numerical value between the two numerical endpoints, unless otherwise indicated. Where a numerical range merely refers to integers within the numerical range, including both end integers of the numerical range, and each integer between the two ends, unless otherwise indicated, each integer is recited herein as directly, such as where t is an integer selected from 1 to 10, and where t is any integer selected from the group of integers consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10. Further, when a plurality of range description features or characteristics are provided, these ranges may be combined. In other words, unless otherwise indicated, the ranges disclosed herein are to be understood to include any and all subranges subsumed therein.
The term "streptozotocin" refers to streptozotocin, also known as streptozotocin, and has the chemical name 2-deoxy-2- [ [ (methylnitrosoamino) carbonyl ] -amino ] -D-glucopyranose, which is an organic compound having the chemical formula C8H15N3O7, and is a pale yellow crystalline powder, soluble in water, lower alcohols and ketones.
Early studies by Robert d.galiano et al showed that increasing angiogenesis contributes to repair of diabetic skin lesions. Linfei Luo et al demonstrated on mice and zebra fish that endogenous lymphatic vessels could serve as a "growth track" to guide neoangiogenesis, which plays an important role in the repair of brain injury following stroke. The present application therefore hypothesizes that in the peripheral circulatory system, or that promotion of diabetic skin lesion repair can be achieved by early induction of lymphangiogenesis and combined use of pro-angiogenic drugs to accelerate cutaneous revascularization.
VEGF is an important group of mediators that promote angiogenesis and increase vascular permeability, and plays a key role in normal development and wound healing. Vascular endothelial cell growth factor A (VEGFA) and vascular endothelial cell growth factor C (VEGFC) can promote endothelial cell division proliferation, proliferation and metastasis, increase vascular permeability and promote neoangiogenesis, and are powerful multifunctional cytokines acting on vascular endothelial cells. VEGFA is most commonly involved in drug studies in vascular endothelial cell proliferation, migration, and microvascular formation. Recent studies have demonstrated that recombinant human vascular endothelial growth factor rhVEGF165 (i.e., VEGFA) is effective in promoting revascularization, facilitating establishment of rodent ischemic group collateral circulation and microvascular generation. Lillian Lim et al have found that release and activation of VEGFC during wound healing promotes lymphangiogenesis. Therefore, by combining VEGFC and VEGFA, the vascular regeneration of the damaged area of the diabetic skin can be effectively improved, and the healing rate and the healing effect of the diabetic wound surface are further improved.
The methacryloylated gelatin (GelMA) hydrogel is synthesized by the reaction of gelatin molecular chains and Methacrylic Anhydride (MA), has higher biocompatibility and good mechanical property as a novel biomedical dressing, is a good drug delivery platform and ideal tissue repair material, and has good slow release effect. The material has excellent biocompatibility, can be cured by ultraviolet light or visible light to form a three-dimensional structure with certain intensity, and is suitable for cell growth and differentiation. The biocompatibility is far better than that of matrigel and fibrin glue, and the properties of the matrigel and the fibrin glue are similar; and simultaneously, the forming performance is far superior to that of collagen, and the collagen is the best choice for replacing the materials.
The drug-carrying system of VEGFA and VEGFC combined with GelMA hydrogel is utilized to compare and analyze the difference of the drug VEGFA and VEGFC for promoting the repair of diabetic wounds by single and combined medication, observe the influence of different drug dosage ratios on the morphology and the function of new blood vessels and lymphatic vessels, and clarify the effect of promoting the generation of blood vessels and lymphatic vessels on vascular regeneration and wound healing.
The application is based on a GelMA hydrogel drug-carrying system, and the wound surface of the diabetic mouse is coated and treated by loading VEGFC and VEGFA so as to accelerate and improve the healing speed and effect of the skin injury part of the diabetic mouse. The treatment method is simple and easy to operate, and has extremely strong clinical application potential.
In one aspect, the application provides a drug delivery system comprising a carrier, VEGFA and VEGFC, wherein VEGFA and VEGFC are both loaded on the carrier.
In a specific example, the mass ratio of VEGFA to VEGFC is (0.8-1.2): 0.8-1.2. For example (0.8, 0.9, 1.0, 1.1, 1.2): (0.8, 0.9, 1.0, 1.1, 1.2).
Optionally, the mass-to-volume ratio of VEGFA to carrier is (400-600) 1, and the mass-to-volume ratio of VEGFC to carrier is (400-600) 1. For example, the mass (ng) volume (ml) ratio of VEGFA to carrier is 400:1, 410:1, 420:1, 430:1, 440:1, 450:1, 460:1, 470:1, 480:1, 490:1, 500:1, 510:1, 520:1, 530:1, 540:1, 550:1, 560:1, 570:1, 580:1, 590:1, 600:1.
For example, the mass (ng) volume (ml) ratio of VEGFC to carrier is 400:1, 410:1, 420:1, 430:1, 440:1, 450:1, 460:1, 470:1, 480:1, 490:1, 500:1, 510:1, 520:1, 530:1, 540:1, 550:1, 560:1, 570:1, 580:1, 590:1, 600:1.
In a specific example, the carrier comprises a methacryloylated hydrogel. It is understood that the methacryloylated hydrogels include, but are not limited to, methacryloylated hyaluronic acid hydrogels, methacryloylated chitosan hydrogels.
The methacryloylated Gelatin (GelMA) is prepared from Methacrylic Anhydride (MA) and Gelatin (Gelatin), and is a photosensitive biological hydrogel material. The material has excellent biocompatibility, can be cured by ultraviolet light or visible light to form a three-dimensional structure with certain intensity, and is suitable for cell growth and differentiation. The biocompatibility is far better than that of matrigel and fibrin glue, and the properties of the matrigel and the fibrin glue are similar; and simultaneously, the forming performance is far better than that of collagen.
Hydrogels have biocompatibility and biodegradability, electrical conductivity, mechanical properties, stress responsiveness, swelling properties, and the like. (1) Biocompatibility and biodegradability in the research of injecting hydrogel for treating bone joint injury and the like, no inflammatory reaction occurs, and good biocompatibility of the hydrogel is proved. The hydrogel can be prepared into high-performance hydrogel with biodegradability by a modifying or compounding means, and has great application potential in implantation intervention and drug delivery.
(2) The swelling and water-absorbing hydrogels have swelling properties capable of absorbing large amounts of water, up to 99% water content, due to the presence of hydrophilic groups in the backbone or terminal chains of their polymeric materials. The hydrogel is used as a medical dressing, can absorb wound exudates and keep the environment moist, can be tightly attached to a wound and is not adhered, bacterial contact is reduced, and secondary wounds caused by adhesion with the wound are avoided.
(3) The stress responsive hydrogel has high water content, high sensitivity, adjustable structure and physicochemical properties, so that the hydrogel can quickly respond to external environment stimulus in the forms of swelling, shrinkage or sol-gel phase transition and the like. The stress of hydrogels can be classified into physical and chemical responses according to the conditions that give rise to the response. Physical response refers to the hydrogel responding to changes in the physical environment, such as thermal, optical, magnetic and mechanical responses. Chemical response refers to the response of the hydrogel to changes in chemical environment, such as pH, ionic strength, etc. Physically responsive hydrogels are commonly used in everyday life, whereas chemically responsive hydrogels are used in biological medicine.
Alternatively, the volume percent of the methacryloylated hydrogel is 14% to 16%. For example, the volume percent of the methacryloylated hydrogel is 14%, 15%, 16%.
The application also provides application of the drug delivery system in preparing a medicine for healing diabetic skin wounds.
In a specific example, the medicament includes a pharmaceutical composition and a pharmaceutically acceptable adjuvant.
Optionally, the auxiliary material is selected from one or more of diluents, binders, disintegrants, lubricants and wetting agents.
Further alternatively, the dosage form of the medicament is one or more of a tablet, capsule, granule, pill, injection and sustained release formulation.
The application also provides a preparation method of the drug carrying system, which comprises the following steps: the vehicle was mixed with VEGFA and VEGFC to prepare a drug delivery system.
Embodiments of the present application will be described in detail below with reference to examples. It should be understood that these examples are illustrative only of the present application and are not intended to limit the scope of the present application. The experimental methods, in which specific conditions are not noted in the following examples, are preferably referred to in the guidelines given in the present application, may be according to the experimental manual or conventional conditions in the art, may be according to the conditions suggested by the manufacturer, or may be referred to experimental methods known in the art.
In the specific examples described below, the measurement parameters relating to the raw material components, unless otherwise specified, may have fine deviations within the accuracy of weighing. Temperature and time parameters are involved, allowing acceptable deviations from instrument testing accuracy or operational accuracy.
Example 1
1. Construction of STZ-induced diabetes mouse model
(1) Experimental animal
SPF-class Balb/C mice, male, 4 w-6 w for week, and 20 g-22 g for body weight.
(2) Main reagent and preparation method thereof
Citric acid, trisodium citrate, streptozocin (STZ)
Preparing a sodium citrate buffer solution: 2.10g of citric acid is added into 100ml of double distilled water to prepare a citric acid mother solution, which is called solution A; 2.94g of trisodium citrate is added into 100ml of double distilled water to prepare sodium citrate mother solution, which is called solution B; a, B solutions were mixed in a ratio of 1:1.32, the pH was measured by a pH meter, and the solution pH was adjusted to 4.0, which was the desired STZ-preparing 0.1mol/l sodium citrate buffer.
Preparation of STZ solution: STZ was dissolved in 0.1mol/l sodium citrate buffer, freshly prepared as a 10mg/ml strength STZ solution, and sterilized by filtration with a 0.22 μm filter. It is prepared in dark place and is used at present.
(3) Modeling method
The mice in the model group were intraperitoneally injected with STZ at a dose of 120mg/kg and the control group was given the same dose of sodium citrate buffer, after a 12h preoperative fasting.
After STZ injection for 2d, fasting blood glucose was measured, and blood glucose higher than 16.7mmol/l was selected for inclusion in the official test.
After STZ injection, blood glucose was measured weekly, weighed, and body weight blood glucose changes were observed.
After the STZ injection is selected for 21d, the phenomenon of polydipsia, polyphagia and polyuria occurs, and the mice with the blood sugar value higher than 16.7mmol/l are subjected to subsequent skin damage experiments.
2. Preparation of medicine-carrying GelMA hydrogel dressing
(1) Preparing 0.25% (w/v) initiator standard solution
(1) 20ml PBS was taken and added to a brown bottle containing 0.05g LAP of initiator.
(2) Heating and dissolving in water bath at 40-50 deg.c for 15 min, and oscillating several times.
(2) Preparing 15% (w/v) GelMA solution
(1) Weighing GelMA with required mass, and placing into a centrifuge tube.
(2) And adding an initiator standard solution into the centrifuge tube, and oscillating to fully infiltrate the GelMA.
(3) Heating and dissolving in water bath at 60-70 deg.c for 20-30 min while shaking several times.
(4) The GelMA solution was immediately sterilized (to prevent low temperature gelation) with a 0.22 μm sterile needle filter.
(3) The drug-loaded GelMA hydrogel dressing is divided into the following three groups:
(1) VEGFA-GelMA treatment group: 100ng VEGFA was added to each 0.2ml GelMA solution.
(2) VEGFC-GelMA treatment group: 100ng of VEGFC was added to each 0.2ml of GelMA solution.
(3) VEGFA-VEGFC-GelMA combination treatment group: 50ng of VEGFA and 50ng of VEGFC were added to each 0.2ml of GelMA solution.
3. Construction of a mouse skin injury model
The mice were anesthetized by inhalation anesthesia, the hair on the back skin was removed by depilatory cream, then the skin was cleaned with medical alcohol, a sterile 6mm diameter skin biopsy punch was used to punch holes in the back, and a complete skin was excised, producing 4 full skin wounds on the back of each mouse. It will be appreciated that other non-surgical or non-invasive means of verification and model construction may be employed.
4. Grouping and administration
Normal mice were divided into a blank control group and a GelMA treatment group; diabetic mice were divided into a blank control group, a GelMA treatment group, a VEGFA-GelMA treatment group, a VEGFC-GelMA treatment group and a VEGFA-VEGFC-GelMA combination treatment group. Mice were anesthetized and 4 full-thickness skin wounds were made at the back, each group being untreated, gelMA-coated, gelMA-drug-loaded coated. Note that the gel was applied to the wound, covering the wound completely, to make it highly consistent with normal skin.
5. Wound healing rate assessment
Each mouse was housed separately after surgery. And observing and photographing every day after the operation to record the wound healing condition, measuring the wound surface area by adopting an Image J Image analysis system, and calculating the wound healing rate R.
Wound healing rate = (S0-Sn)/S0
Where S0 represents the initial wound area and Sn represents the wound area at different time points.
Example 2
Wound healing comparison of whether Normal mice were hydrogel coated
The experimental method comprises the following steps: 6 normal mice were anesthetized, back hair was removed, a sterile 6mm diameter skin biopsy puncture outfit was used to perforate the back and remove a complete skin, and 4 full skin wounds were made symmetrically at the back of each mouse. 3 mice were wound-blanked to heal naturally, and 3 were coated with 15% GelMA. Note that the gel was applied to the wound, covering the wound completely, to make it highly consistent with normal skin. A visual map of the wound was recorded daily with a digital camera.
Wherein, FIG. 1 is a normal mouse skin injury site healing process monitoring. A in fig. 1 is a visual diagram of an damage repair process of uncoated GelMA and coated GelMA; b in fig. 1 is a trend chart of wound healing rates for different groups. I.e., after normal mice had skin injury, the skin of mice in the blank treatment group was repaired for about 8 days, and as shown by the results B in fig. 1, the wound area slightly increased and then gradually decreased the next day after injury. The GelMA group is coated to show that the skin damage repair period is 8 days, but the GelMA has better wound convergence effect, and the wound area is greatly reduced. Compared with the blank group, the wound area of the wound is obviously contracted in the next day, and the scar area after repair is obviously smaller than that of the blank group.
The results show that: gelMA has good effect of astringing skin wound, but does not influence the damage repair cycle, and simultaneously has good drug loading and slow release functions, so that the GelMA is suitable for drug test research of skin damage repair.
Example 3
Wound healing comparison of hydrogel-coated or not diabetic mice
The experimental method comprises the following steps: 6 diabetic mice were anesthetized, back hair was removed, a sterile 6mm diameter skin biopsy puncture outfit was used to perforate the back and remove a complete skin, and 4 full skin wounds were made symmetrically at the back of each mouse. 3 mice were wound-blanked to heal naturally, and 3 were coated with 15% GelMA. Note that the gel was applied to the wound, covering the wound completely, to make it highly consistent with normal skin. A visual map of the wound was recorded daily with a digital camera.
Among them, fig. 2 is a monitoring of the healing process of skin injury site of diabetic mice. A in fig. 2 is a visual diagram of the damage repair process of the uncoated GelMA and the coated GelMA; b in fig. 2 is a trend chart of wound healing rates for different groups.
After the skin of the diabetic mice was damaged, the skin of the mice in the blank treatment group was repaired for about 21 days, and as shown by the B results in fig. 2, the wound area slightly increased and then gradually decreased in the following day after the damage. Compared with normal mice, the wound healing period of the diabetic mice is obviously prolonged, and the wound can be repeatedly bleeding and worsened in the healing process. The GelMA group was coated to show that the skin damage repair period was 21 days, but GelMA had a good wound astringing effect, which greatly reduced the wound area. Compared with the blank group, the wound area is obviously contracted in the next day, the scar area after repair is obviously smaller than that of the blank group, the healing process of the middle wound is stable, and repeated bleeding and deterioration of the wound do not occur.
The results show that: the repair process of skin injury of the diabetic mice is obviously longer than that of normal mice. Similarly, gelMA has good effect of astringing skin wound, but does not influence the damage repair period, and simultaneously has good drug loading and slow release functions, so that the GelMA is suitable for subsequent drug test research of diabetic skin damage repair.
Example 4
Wound healing comparison of hydrogel-coated individual-loaded VEGFA, VEGFC and VEGFA for diabetic mice
The experimental method comprises the following steps: preparing 15% GelMA solution, sterilizing with 0.22 μm sterile needle filter, and adding 100ng VEGFA to obtain VEGFA-GelMA solution; adding 100ng of VEGFC to prepare a VEGFC-GelMA solution; 50ng of VEGFA and 50ng of VEGFC were added to prepare a VEGFA-VEGFC-GelMA solution.
9 diabetic mice were anesthetized, back hair was removed, a sterile 6mm diameter skin biopsy punch was used to punch a hole in the back and a complete skin was excised, and 4 full skin wounds were symmetrically made at the back of each mouse. 3 were coated with VEGFA-GelMA solution, 3 were coated with VEGFC-GelMA solution, and 3 were coated with VEGFA-VEGFC-GelMA solution. Note that the gel was applied to the wound, covering the wound completely, to make it highly consistent with normal skin. A visual map of the wound was recorded daily with a digital camera.
Among them, fig. 3 is a monitoring of the healing process of skin injury parts of diabetic mice coated with different drugs. A in fig. 3 is a visual diagram of a damage repair process of coating VEGFC-GelMA; visual images of damage repair processes coated with VEGFA-GelMA; visual images of damage repair processes of the coated VEGFA-VEGFC-GelMA; b in fig. 3 is a trend chart of wound healing rates for different groups.
After the skin of the diabetic mice is damaged, the skin of the mice coated with the VEGFC-GelMA and the skin of the mice coated with the VEGFA-GelMA are repaired for about 12 days. In the repair process of the VEGFC-GelMA group, a certain bleeding phenomenon exists in a wound, and the repair process of applying the VEGFA-GelMA group is more stable. However, the group with the VEGFA-VEGFC-GelMA effect is obviously superior to other treatment groups, and the wound repair can be realized within 9 days. Therefore, the drug treatment system of VEGFA-VEGFC-GelMA is beneficial to repairing skin injury of diabetic mice, and has extremely strong clinical application potential.
The above examples merely represent a few embodiments of the present application, which facilitate a specific and detailed understanding of the technical solutions of the present application, but are not to be construed as limiting the scope of the claims. It should be noted that it would be apparent to those skilled in the art that various modifications and improvements could be made without departing from the spirit of the present application, which would be within the scope of the present application. Further, it will be understood that various changes or modifications may be made to the present application by those skilled in the art after reading the foregoing teachings, and equivalents thereof will be within the scope of the present application. It should also be understood that those skilled in the art, based on the technical solutions provided in the present application, can obtain technical solutions through logical analysis, reasoning or limited experiments, all fall within the protection scope of the claims attached to the present application. The scope of the patent application is therefore intended to be limited by the content of the appended claims, which description and drawings may be interpreted accordingly.
Claims (10)
1. A drug delivery system comprising a carrier, VEGFA and VEGFC;
wherein VEGFA and VEGFC are supported on the carrier.
2. The drug delivery system of claim 1, wherein the VEGFA and VEGFC are in a mass ratio of (0.8-1.2): 0.8-1.2;
optionally, the mass ratio of the VEGFA to the VEGFC is 1 (0.8-1.2).
3. The drug delivery system of claim 1, wherein the mass to volume ratio of VEGFA to the carrier is (400-600) ng 1ml;
the mass volume ratio of the VEGFC to the carrier is (400-600) ng/1 ml.
4. A drug delivery system according to any one of claims 1 to 3, wherein the carrier comprises a methacryloylated hydrogel;
optionally, the methacryloylated hydrogel comprises one or more of methacryloylated hyaluronic acid hydrogel, methacryloylated chitosan hydrogel.
5. The drug delivery system of claim 4, wherein the volume percent of methacrylic acid in the methacryloylated hydrogel is 14% to 16%.
6. Use of the drug delivery system of any one of claims 1 to 5 for the manufacture of a medicament for the healing of diabetic skin wounds.
7. The use according to claim 6, wherein the medicament further comprises pharmaceutically acceptable excipients.
8. The use according to claim 6, wherein the auxiliary material is selected from one or more of diluents, binders, disintegrants, lubricants and wetting agents.
9. The use according to any one of claims 7 to 8, wherein the pharmaceutical dosage form is one or more of a tablet, a capsule, a granule, a pill, an injection and a sustained release formulation.
10. A method of preparing a drug delivery system comprising the steps of: the vehicle was mixed with VEGFA and VEGFC to prepare a drug delivery system.
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