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The Construction of Photo-cleavable Small Molecular Hydrogels Based on Peptides and Their Drug Delivery

Author: LiuHanXia
Tutor: ChenXueMei
School: Hubei University of Technology
Course: Chemical Engineering
Keywords: small molecular hydrogels peptides self-assembly photolinker drugrelease
CLC: TQ460.1
Type: Master's thesis
Year: 2013
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Abstract


Gelator of small molecular hydrogels formed three-dimensional networknano-structure by peptides self-assembly in aqueous solution, which can be used asefficient drug carriers, and they had good biocompatibility, biodegradable, simplesynthesis synthetic and preparation process, are a promising new drug carrier. Researchhas shown that the means of these small molecules hydrogels releasing drugswere multiple, such as hydrolysis, temperature control, enzymatic, lighting irradiationand so on, potential application of all kinds of of intelligent hydrogels have been one ofthe hot topics recently. This paper firstly explored a photolinker to connect thehydrophilic and hydrophobic groups for short peptides to produce molecularhydrogelators, then applied it to research on drug delivery systems by photo-irradiation.The test results will provide the basic data for design of biomaterials data.A photocleavable nitrobenzyl ester group introduced in the backbone ofself-assembling peptides was synthetized by acetovanillone and ethyl4-bromobutyrate,then connect a gelator and a hydrophilic group using standard Fmoc-peptide systhesis. Itrevealed that the photocleavable linker as one part of hydrophobic capping group couldcommendably form molecular hydrogel after a series of trial and error in PBS. Themorphology arrangement of the targeted peptide was tested by TEM, a fibrous meshstructure can gain best application of drug delivery and tissue engineering. Meanwhile,this also proved the photolinker didn’t affect short peptides balance of hydrophilicityand hydrophobicity.Subseqyently, disulfide bonds was leaded-in the pharmaceutical polypeptidemolecules, stable hydrogels were prepared by chemical reduction method to inducedpeptides self-assembly. This approach of fabricating polydispersity drug system hasgeneral applicability: the inherent intracellular reduced glutathione is highbiocompatibility, controllable. Restoring conversion rate of the experiment shown thatthe carring load rate of four drugs-peptides were very high, more than90%in paper.These hydrogels also had been made a more comprehensive analytical characterization,the results implicated that the they also had a cross-linked three-dimensional networkstructure, forming different shape and size, of the fiber, respectively. The strengthproperties of macroscopic mechanical also were different. Four hydrogels all releasedthe hydrophobic anti-imflammatory drugs and the gel-sol phase transition whenultraviolet light irradiated, besides the experiments showed good results.Further more, the experiments of durg release in vitro selected Naproxen-peptides hydrogel as a representative of the photo-controlled drug delivery system inthis paper. Dark and UV irradiation were placed alternately, observing the release of thedrug molecules. The experimental results conveyed this self-vector system not only hada high drug loading capacity, but aslo not occured suddenly explosive release. What’smore, the hydrogels might be formed in a spatial and temporal way.Thephoto-controllable gel-sol phase transition and drug release might be used as a platformfor ‘on demand’ release of therapeutic agents.

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