Controlled release of paclitaxel from microemulsion containing PLGA and evaluation of anti-tumor activity in vitro and in vivo.
The main objective of this study was to develop an optimal paclitaxel microemulsion prepared by self-microemulsifying drug delivery system (SMEDDS) which is a mixture of paclitaxel, tetraglycol, Cremophor ELP, and Labrafil 1944 and a paclitaxel microemulsion containing poly(D,L-lactide-co-glycolide) (PLGA) in order to offer controlled release of paclitaxel. To achieve this goal, paclitaxel and PLGA were dissolved by solubilizer like tetraglycol. There was not observed any change in molecular weight of PLGA after being solubilized by tetraglycol. The droplet size for all of the formulation of microemulsion was found in the range of 45-270nm by dynamic light scattering (DLS). It was observed that the droplet size of microemulsion without PLGA was smaller than that of microemulsion containing PLGA by transmission electron microscopy (TEM). The droplet of microemulsion containing PLGA was almost of spherical shape with smooth surface and there was no aggregation or adhesion among droplet of microemulsion by atomic force microscopy (AFM). The release behaviour of paclitaxel from microemulsion containing PLGA having various molecular weights (8K, 33K, and 90K) exhibited a biphasic pattern characterized by a fast initial release during the first 48h, followed by a slower and continuous release for 144h, in contrast that the release of paclitaxel from microemulsion without PLGA was finished during 24h. This result was identical with the result of anti-tumor activity in vitro of paclitaxel from microemulsion containing PLGA against human breast cancer cell line MCF7 and this formulation enhanced anti-tumor activity in vivo compared with microemulsion without PLGA against SKOV-3 human ovarian cancer cells bearing nude mice model.
Kang
Bok Ki
BK
Department of Polymer.Nano Science and Technology, Chonbuk National University, 664-14, Duckjin Gu, Jeonju 561-756, Republic of Korea.
Chon
Se Kang
SK
Kim
Seon Hwa
SH
Jeong
Sang Young
SY
Kim
Moon Suk
MS
Cho
Sun Hang
SH
Lee
Hai Bang
HB
Khang
Gilson
G
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000145:classification / Q000379:methods*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004357:Drug Synergism; D004655:Emulsions / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D008832:Microchemistry; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D036103:Nanotechnology / Q000379:methods; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012995:Solubility / Q000187:drug effects; D013678:Technology, Pharmaceutical / Q000379:methods; D016896:Treatment Outcome
D004655:Emulsions; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel