Based On "Drug Carrier Integration" PAE-HAM-Gels:Preparation And Pharmacodynamics Evaluation

Research background Hypertrophic Scars（HS）is a kind of refractory skin disease that is special in humans.Due to various factors and lack of ideal animal models,it has been a problem in the field of wound repair.Traditional Chinese medicine believes that HS is a snoring disease,and the rule is soft and firm,blood stasis,and should be combined with prevention and treatment.In this paper,the bioadhesive material-helix aspersa muller was designed as a carrier for delivery,and the active ingredient of the Chinese medicine peony bark,paeonol,was transmitted to exert a synergistic inhibitory effect,and a novel nanogel preparation was prepared for safety and drug release performance.And pharmacodynamic studies provide a dermatological treatment for the prevention and treatment of hypertrophic scars.Objective To develop a helix aspersa muller-Paeonol composite gel to optimize the formulation and preparation process of helix aspersa mullerpeicalidin nanoparticles,and to investigate its transdermal performance and dermal retention effect in vitro,and to carry out skin irritation and depression in New Zealand rabbits.The effect study provides a theoretical basis for the further study of the prevention and treatment of hypertrophic scars.Method:（1）Quantitative determination of the active constituents of helix aspersa muller,to investigate the physicochemical properties and biocompatibility of helix aspersa muller.（2）Preparation and quality of helix aspersa muller-Paeonol nanoparticles.The encapsulation efficiency was used as the evaluation index,and the single factor experiment screened out significant factors.The BoxBehnken response surface method was preferred for the preparation of nanoparticles,the morphology of nanoparticles was observed by transmission electron microscopy,and the particle size and Zeta potential were determined by laser particle size analyzer.Preparation of helix aspersa muller-Paeonol composite gel.（3）Quality of helix aspersa muller-Paeonol composite gel.Investigate the quality properties,including traits,viscosity,centrifugation and determination.Investigate the retention of dermis and compare the dermal retention and transdermal rate of snail mucilage-peponin complex gel and paeonol gel in the skin of three different animals.curve.The skin irritation was examined by the left-right contrast method to observe whether the skin had erythema and edema,and the skin of the administration site was HE stained.（4）To establish a rabbit ear hypertrophic scar model,the New Zealand rabbits were randomly divided into a model group,a blank group,a positive drug group,a helix aspersa muller gels group（HAM-Gels）and a helix aspersa muller-Paeonol composite gels group（PAE-HAM-Geles）,the scar hyperplasia rate of each group was calculated,the scar hyperplasia index（SEI）of each group was measured,and the tissue hyperplasia after HE staining and Masson staining was observed under light microscope.Double antibody sandwich enzyme-linked immunosorbent assay（ELISA）The expression levels of TGF-β1 in each group were examined.Result:（1）A qualitative and quantitative detection method for helix aspersa muller can be obtained,and the content of the active ingredients allantoin and glycolic acid can be simultaneously determined.The helix aspersa muller used in this experiment has good biocompatibility and no skin irritation to SD rats.（2）The optimal preparation process of helix aspersa muller-paeonol nanoparticles is as follows: weigh 26 mg of paeonol and 2 m L of absolute ethanol,and mix by ultrasonic,400 r·min-1 magnetic stirring at 30 ℃ and slowly injecting at a constant rate To 0.6g helix aspersa muller（5m L p H7.4 PBS buffer solution）;continue to stir for 20 minutes after the completion of the drop,decanted the ethanol,and the obtained solution was sonicated in an ice water bath for 10min（120W,ultrasound 2s,intermittent 2s）,the encapsulation efficiency value of the nanoparticle was（81.64±2.24）%,the average particle size（182.43±16.8）nm,and the Zeta potential（8.33±0.90）m V.（3）The viscosity of helix aspersa muller-paeonol composite gels is between 6.6⁷.4 Pa·S,the p H value is between 7.0 and 7.5,and the content is（3.04±0.08）mg·g^-1;The in vitro release profile of the helix aspersa mullerpaeonol composite gels was in accordance with the Higuchi equation,and the dermal retention effect was significant.No skin irritation to New Zealand rabbits.（4）The scar hyperplasia rate of the helix aspersa muller-paeonol composite gels group was 62.50%,which was lower than other groups;the SEI was（2.17 ± 0.33）,and the TGF-β₁ was（815.4 ± 34.69）ng·L^-1,and the model group The difference was statistically significant（P < 0.01）.Compared with the model group,the helix aspersa muller-paeonol composite gels group has fewer collagen fibers and muscle fiber cells,and the arrangement is loose,the chondrocytes are arranged more regularly,and the inflammatory cells are less.Conclusion The quality control method established by this subject meets the requirements of the pharmacopoeia;The Box-Behnken effect surface method can be used to optimize the preparation process of paeonol nanoparticles.The helix aspersa muller-paeonol complex gels has a sustained release effect,and the dermal retention is significant;helix aspersa muller-Paeonol composite gels has certain therapeutic effect on hypertrophic scars in rabbit ears,preparations are safe,no skin irritation and have good application prospects.