Preparation And Characteristics Study Of Poly (Ethylene Oxide)-Poly(Lactic Acid) Thermo-sensitive Drug Delivery System

Pharmaceutical excipient is an important part of pharmaceutical preparations because it plays as key role in improving the performance of drug release profile, bioavailability and reducing the side effect. More and more scientists pay attention to development of new pharmaceutical excipient in recent years. The system of drug-loaded hydrogel in situ is used widely in the drug delivery system. Because it can retard the release of drug, especially the system can release the drug in a same site. This paper focus on the preparation of thermo-sensitive injective gel system in situ by new-style polyethylene oxide-polylactic acid-polyethylene oxide (PEO-PLA-PEO) triblock copolymer and its potential application.The main contents and conclusions in this paper are as follows:1. To synthesis polylactic acid- polyethylene oxide (PLA-PEO) diblock copolymer from lactic acid and monomethyl polyethylene glycol (mPEO) with direct polymerization method. The IR, ~1H-NMR and the GPC has attributed to examine the molecular structure and the molecular weight of product. The research discovered that the factors such as pretreatment, reaction pressure, reaction temperature, reaction time, catalyst sort and amount can influence the molecular weight of product. under the condition of reaction time is 7 hours, reaction temperature is 160℃, the amount of catalyst is 0.8 wt%. The molecular weight and structure of product are characterized by FTIR, ~1H-NMR and GPC. It is found that the molecular weight of PLA block which is prepared as the craft mentioned before is among 16000-20000.2. The HMDI is used as link agent reacts with end hydroxyl in the PEO-PLA to synthesis PEO-PLA-PEO. And the PEO-PLA-PEO aqueous solution is prepared to research the influences of solution concentration and the temperature changes on the PEO-PLA-PEO system's phase transform characteristic. 1H-NMR and GPC are attributed to examined the molecular structure and the molecular weight of product; the PEO-PLA-PEO aqueous solution is prepared for characterization with dye solubilization method, dynamic light scattering studying (DLS) and differential scanning calorimetry (DSC) for studying the micellization behaviors of triblock copolymer solution. It is found that the triblock copolymer solution can reversibly transformation between the state of gel and sol among the temperature of 35℃-50℃. And, the spot of phase changing appears at 48℃and the other spot appears at 38℃.Moreover, the interact force which forms the micelle in the solution is one of important reasons to cause the phase transformation.3. Carboxymethyl Chitosan (CMCTS) is chosen as material, the calcium chloride and the vanilla are selected as dual crosslinking agents to prepared drug-loaded microcapsules. The outlook and inner structure of microcapsules are observed by SEM. As the stipulation of Chinese Pharmacopoeia, the drug release characteristic of microcapsules is studied. The electrostatic force between calcium ion and the canboxymethyl, and the Schiff base which is formed between the aldehyde of vanillin and amino of CMC are the reasons to produce microcapsules. The vanilla is the national legal edible spice and widely applies to drink, food, cosmetics and tobacco. The CMC microcapsules crossliked with Ca (II) and vanilla is easy to prepare, non-toxic and security, therefore, the microcapsules possibly is a kind of valuable new drug carrier.4. The microcapsules of carbomethyl chitasan is prepared and mixed with the thermo-sensitive system which is prepared by polyethylene glycol-polylactic acid-polyethylene glycol. The mechanical capacity and drug release profiles of the system are characterized. It is found the mechanics capacity of compound system is changing with the change of temperature and the phase transform of itself. In sol state, the system has any mechanical capacity, but it increases in soft gel state (about 45℃), and the mechanical capacity achieves to maximum in gel state about 38℃-39℃. Compared to the microcapsules and matrix, the gel system has the outstanding drug release profiles which can prolong the drug releasing period to 30h-40h. The result indicates that this system can effectively achieve the goal of "injection in situ", then releases contained drug slowly. So it is hopeful to be applied to cure the illness of some specific spot such as joint cavity and soft tissue.