Preparation And Release Profiles In Vitro Of Analgesic And Anti-inflammatory Drugs Loaded Microspheres

Chronic pain is a disease that has become a serious medical and social problem. The longest duration of local anesthetics acting are not more than 12 h after administration, it cannot meet the need of long time pain treatment. Inflammation was a common complication of disease, which also exists in the process of the treatment of chronic pain. Ropivacaine (ROP) is a new kind of amide local anesthetics agents, which attracted more attention because of the excellent effect of anesthesia. Betamethasone dipropionate (BDP) is an anti-inflammatory bactericidal drug commonly used in the treatment of bacterial infection and inflammation in the treatment of complications. We chose the poly(ethylene glycol) methoxy-poly(D, L-lactic acid) block copolymers (PELA) as the matrix material, prepared dual-drug co-loaded microspheres by the method of O/W emulsion evaporated solvent, and studied the drug release behavior of microspheres.The PELA copolymers were successfully synthesized by the ring opening polymerization of D,L-lactide in the presence of poly(ethylene glycol) methoxy (mPEG, Mn=2000Kda), the stannous octoate was chosen as the catalyst. The structure and property of PELA copolymers were characterized by using FTIR,1H-NMR, GPC, DSC and CA. Results showed that: the copolymers have the anticipative structure and the molecular weight was 1.2×104 g/mol (PELA-1),2.2×104g/mol (PELA-2),3.7×104 g/mol (PELA-3),5.5×104g/mol (PELA-5) and 7.3×104 g/mol (PELA-7). With the increase of PEG content in the copolymers, the glass transition temperature and water contact angle of the copolymers were decreased.The ROP and BDP co-loaded microspheres based on PELA copolymers were prepared by O/W solvent evaporation method. The diameter of different microspheres was in range of 40～60μm. With the content of PEG increased in the copolymers, the drug loading and encapsulation efficiency of microspheres decreased. Because PEG is the hydrophilic segment, the copolymers with the high content of PEG can decrease the compatibility of the hydrophobic drugs. The microsphere of PELA-7 has the highest drug encapsulation efficiency of ROP and BDP were 81% and 77%, respectively.In vitro release experiments of microspheres were conducted at 37℃ in the release medium with a pH value of 7.4. The results shown that dual-drug microspheres owned sustained-release properties and can be released for two weeks. The microspheres of PELA-1 has the highest cumulative release percentage of ROP and BDP, a total of 95% and 90% sustained release were achieved, respectively. The release mechanism of microspheres was fitted to Ritgers-peppas model, and it showed that the drug release process was mainly controlled by diffusion.