Preparation Of Human Hair Keratin Intelligent Drug Carrier And Research On Drug Sustained Release

Chemotherapy is one of the most popular treatments for cancers.However,conventional chemotherapy lacks of specific recognition and induces severe side effects on normal tissues or normal cells.At present,a wide variety of nano-smart drug carriers based on stimuli-responsive polymer materials have aroused much attention due to their advantages of increasing solubility of anti-tumor drugs in water,targeting and reducing the side effects of drugs.As a natural biomacromolecule,keratin has good bioactivity,biocompatibility,biodegradation,and natural abundance and has broad prospects in the application of drug carriers.In this work,human hair keratin was selected as a carrier to prepare the stimuli-responsive nano-smart drug carrier systems by different methods,and its applications to drug delivery systems were exploried.(1)Preparation of acid sensitive nanoparticles based on DOX conjugated keratinKeratin-DOX prodrug was first prepared by hydrazone bond coupling.The pH-triggered DOX-loaded keratin nanoparticles were prepared by desolvation thereafter.In vitro release experiments showed that the drug-loaded nanoparticles exhibited a pH responsive character.Drug release was obvious in acidic environment while hardly release was observed in the simulated physiological environment.(2)Preparation of drug-loaded micelles based on Keratin-PEG conjugated compoundAmphiphilic keratin-poly(ethylene glycol)(PEG)conjugated compound was successfully synthesized via Michael addition reaction(thiol-ene click chemistry).Small-molecule hydrophobic drug(DOX)and keratin-poly(ethylene glycol)(PEG)conjugated compound can self-assemble into micelles in aqueous media.The results showed that the drug loading rate of the micelles was as high as 21%.The release amount indicated that the drug-loaded micelles were dual-responsive to GSH and enzyme.In the presence of enzyme,the drug was released more thoroughly from the carriers.(3)Preparation of drug-loaded micelles based on Keratin-PMPC conjugated compoundFirstly,keratin-polyphosphorylcholine(PMPC)conjugated compound was prepared by chain transfer radical polymerization.Then,Keratin-PMPC conjugation and hydrophobic drug(DOX)can self-assemble into micelles in aqueous media.The micelles were characterized with nuclear magnetic resonance spectroscopy,fluorescence spectrometer,dynamic light scattering,and transmission electron microscope,in vitro release by dialysis and MTT assay.The results showed that drug-loaded micelles were solid spheres and with the diameter of ca.91 nm.Moreover,drug-loaded micelles were dual-responsive to GSH and enzyme and exhibited enhanced inhibitory efficiency against A-549 cells.