The polymer-alloys method as a new preparation method of biodegradable microspheres: principle and application to cisplatin-loaded microspheres

Autor: Takehiko Suzuki, Akihiro Matsumoto, Yasuhisa Matsukawa, Masao Kobayashi, Hiroyuki Yoshino
Rok vydání: 1997
Předmět:
Zdroj: Journal of Controlled Release. 48:19-27
ISSN: 0168-3659
DOI: 10.1016/s0168-3659(97)00031-x
Popis: The new preparation method for multi-reservoir type microspheres was investigated on the basis of the phase separation of poly( d l -lactic acid) (PLA) and poly( d l -lactic-co-glycolic acid) (PLGA). Phase diagram study suggested that, in the PLA-PLGA-methylene chloride ternary system, the distinctive phase separation occurred when the total polymer concentration exceeded a critical level. The critical polymer concentration inducing this phase separation was found independent of the PLA/PLGA ratio but highly dependent on the solvent species, molecular weight, or lactide/glycolide ratio of PLGA. When various amino acid powders were added to the resultant biphasal polymeric solution, each powder was distributed either to the PLGA-rich phase or to the PLA-rich phase depending on its solubility parameter. It was also found that cisplatin powder was completely distributed in the PLGA-rich phase. Utilizing these findings, the preparation of the multi-reservoir type microspheres of cisplatin was tried. The PLGA-PLA biphasal polymeric solution dispersing the drug powder was emulsified, and then solidified by the solvent evaporation method. Microscopic observation proved that the obtained microspheres have the unique `polymer alloys' structure and the drug was distributed in the internal phase (PLGA-rich phase). The encapsulation efficiency was almost 100% at 10% loading. The in vitro dissolution study revealed that the release of cisplatin lasted 45 days without initial burst.
Databáze: OpenAIRE
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