Study A Novel Nanoscale Permeation Enhancer Based On ?-CD-grafted Hyperbranched Polyether For Transfermal Insulin Delivery

ObjectiveFrequent subcutaneous injection of insulin can cause local inflammation,fat atrophy and fatty malnutrition,which bring great pain to the patients.Therefore,there is an urgent need to develop non-injectable insulin administration techniques.Transdermal route of administration has become a hotspot in this field because of its advantages of easy absorption,avoidance of liver first pass effect,drug release and improvement of patient compliance.This paper aims to synthesize a new type of nano-penetration enhancer,increase the transdermal administration of insulin,to achieve good control of blood sugar.MethodHyperbranched poly glycidyl ether(HPG)was synthesized by anionic ring opening polymerization,and HPG-g-CD copolymer was obtained by introducing cyclodextrin(?-CD).The nanoparticles loaded with insulin were constructed by nanotechnology and self-assembly method.The particle size and potential were analyzed by dynamic light scattering.The drug loading and entrapment efficiency were evaluated.The in vitro release behavior of insulin was studied.The transdermal effect of insulin was quantitatively observed by laser confocal microscopy,and the permeation of insulin through the skin was quantitatively analyzed by HPLC.H & E staining was used to determine the irritation of rat skin from the perspective of histopathology.The feasibility of HPG-g-CD nanoparticles as transdermal delivery of insulin was evaluated comprehensively.ResultBy adjusting the mass ratio of HPG-NH2 and 6-OTs-?-CD,the HPG-g-CD3 polymer with better drug loading was screened and confirmed by NMR and IR spectra.The particle size is about 200 nm,the zeta potential is +28.3 mV ~ +45.5 mV,and the particle size of the nanoparticles increases with the increase of ?-CD ratio.The nanoparticles can effectively load insulin,the encapsulation efficiency can be as high as 85 %,and the insulin encapsulation rate gradually increases with the increase of ?-CD,but there is no significant difference in drug loading rate.The in vitro release of insulin showed that the release rate and the cumulative release percentage of insulin increased with the increase of ?-CD at pH 7.4.Animal transdermal test results show that over time,FITC-labeled insulin-loaded group reached the dermis layer of the skin in vivo,but the free insulin suspension group only remained on the skin surface,indicating that HPG-g-CD promotes insulin absorption.The in vitro transdermal test of rats also showed that HPG-g-CD nanoparticles were significantly higher than in the insulin solution group at the same time,and further confirmed that HPG-g-CD nanoparticles could increase insulin transdermal absorption.Moreover,the nanoparticles did not induce tissue inflammation and showed good biocompatibility.ConclusionIn this paper,we prepared HPG-g-CD copolymer with good biocompatibility.The self-assembly technique was used to construct homogeneous nanoparticles,which could effectively load insulin,promote insulin transdermal absorption and do not induce tissue inflammation.The novel nanoscale permeation enhance provides new ideas and new strategies for insulin administration,and provides the theoretical basis for the safe and effective treatment of diabetes in clinical insulin.