| Carmustine (BCNU), relatively high lipid solubility and low molecular weight, is widely used for the treatment of maglignant gliomas. However, BCNU is limited by its systemic toxicity and characteristic, such as its water-insolution and short half life. In order to solve these problems, the following work has been done in this dissertation.The aim of this study was the development of a veterinary dosage form constituted by injectable biodegradable microspheres designed for the subcutaneous release of BCNU and paclitaxel, two chemotherapeutic drugs. Poly(D,L-lactide) (PDLLA) microspheres were prepared by spray-drying method, using the drug-to-polymer weight ratios 1:9 and 1:5, blank microspheres (1.5% w/v) were prepared as a comparison. Microparticles were characterized in terms of morphology, encapsulation efficiency, and in vitro drug release behavior. Through Scanning electronic microscope (SEM) the shape and size of the microspheres were obtained. The microparticles had a spherical shape; particle size ranged from 1 to 5μm, dependent on drug loading. Microspheres were able to control the in vitro release of the drug: approximately 90% to 100% of the BCNU was released over 30 days, and 50% to70% paclitaxel was released over one month. So in this article we have discussed the cause of the burst drug release of BCNU. In vitro drug release results showed that the microspheres had shown certain sustained release characteristics, and the BCNU-PDLLA microspheres showed higher burst effect and significantly faster release of drug from PDLLA samples. The results of cyto-toxicity test demonstrated that drug-loaded microspheres had higher antitumor activity, compared with free drug, and sustained drug release character was achieved as well Based on these results, BCNU/ paclitaxel -loaded PDLLA microspheres may be useful for local delivery of the antineoplastic drug to the tumor, avoiding tumor recurrence in small animals, and may decrease the formation of distant metastases.
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