Enzymatic Degradation Of Poly L-lactic Acid Electrospun Fibers And Hollow Microspheres Of Drug Release

Synthetic method of a-hydroxyl octanoic acid and 3,6-dihexyl-1,4-dioxane-2,5-dione was improved and optimized by using heptaldehyde as the starting material via the process of nucleophilic substitution,displacement reaction,acid hydrolysis,deaminization by alkalinization and the process of dehydration of acid catalysis respectively. The improved method increased the yield of a-hydroxyl octanoic acid to 77%. The improved method ensured the material to react thoroughly at every step for synthesizing a-hydroxyl octanoic acid therefore increasing the utilance of material and decreasing the waste of reactant.Polyester polymer was synthesized and electrospinned by dry method:poly L-lactide with high molecular weight and low poly dispersitu index was prepared by melting-polymerization method. a-hydroxyl octanoic was synthesized by dehydration modified process.and its was synthesized by ring opening polymerization at melting state. PEG blocked poly L-lactic acid was electrospun and condition for spinning was optimized by scanning electronic microscope observation. Meanwhile, PEG-PHO and PEG-PCL was respectively mixed with PEG-PLLA and electrospun. Fibers with no phase separation was obtained by mixture organic solution electrospinning.Ultra-fine fibers with magnolol entrapped was prepared by solution from single polymer PEG-PLLA.Fibers with 10%,20% and 30% mass ratio of drug loading was prepared. By SEM onservation and WAXD detection, magnolol could be entrapped in fibers perfectly. Drug burst release amount was small. At prior period of drug release experiment, profiles fitted to a=kt1/2 equation. As the drug amount became bigger, degradation of fibers become slower. And compared to fibers with 10% magnolol loaded release, fibers with 20% and 30% drug loaded release drug slower. Lipophilicity of magnolol lead to weak moisturation of release media onto fiber surface and into fibers inner part. As degradation of fibers became slower, drug release speed became slower.PLLA and PEG-PLLA was used to prepare ultra-fine fibers by solution direct electrospinning.10% and 20% drug to mass ratio of drug loading was prepared. By observation of SEM, ibuprofen was perfectly entrapped in the fibers. Drug release experiment indicated that drug burst release was obvious for that in PEG-PLLA fibers but not for that in PLLA fibers. As higher as concentration of proteinase K in release media became, drug release became faster and PEG blocked PLLA fibers was more easily be affected by proteinase K and release drug faster than that of PLLA fibers. The release profile could be fitted for a=kt1/2 at two stage except for burst release phase. Fibers with 20% drug loaded release drug more faster than that with 10% drug loaded irrespect of the fiber was spun from PLLA or PEG-PLLA.Ultra-fine fibers with ibuprofen entrapped was spun from PEG-PLLA和PEG-PHO composite organic solution. And ultra-fine fibers was also spun from this kind of composite solution to entrap doxorubicin hydrochloride by emulsification-electrospinning process. It was found that as though as 5% mass ratio of PEG-PLLA was replaced by PEG-PHO with molecula weight of about 5000,the fibers would block the fibers from being degradated.For this kind of fibers,1 week cumulated drug release amount was lower than that of with no PEG-PHO added. Just a little addition of low molecula weight polymer into PLLA fibers could prohibit fibers from being degradated.PEG-PLLA and PLLA was used respectively to prepare hollow microspheres with Gemcitabine entrapped by double emulsification process.There were holes existing on microspheres prepared from PLLA. And there were only tiny grid-like patterns on microspheres. From microsphere's cross section by ESEM observation, honeycomb structure was found in both kind of mirospheres. Particle size of two kind of microspheres are almostly the same which were 270±109.7μm and 279±127.2μm respectively. PEG segment in spheres lead to burst release of drug at the beginning and thorough release in the end especially for that there was enzyme in releae media. There was no burst release in PLLA sphere and although under proteinase K degradation, there was unreleased drug remained in inner sphere in the end. After about one month, when there was no proteinase K in release media, less than 40% of loaded drug was released from PLLA sphere and about 70% from PEG-PLLA. When there was proteinase K in release media, about 50% of loaded drug was released from PLLA sphere and more than 70% release from PEG-PLLA and even 100% for that in release media with 10μg/mL proteinase K added.