Preparation, characterization and in vitro cytotoxicity of indomethacin-loaded PLLA/PLGA microparticles using supercritical CO2 technique.
In this work, indomethacin-loaded poly(l-lactic acid)/poly(lactide-co-glycolide) (IDMC-PLLA/PLGA) microparticles were prepared using solution-enhanced dispersion by supercritical fluids (SEDS) technique in an effort to obtain alternative IDMC formulation for drug delivery system. Surface morphology, particle size and particle size distribution, drug encapsulation efficiency, drug release kinetics, in vitro cytotoxicity and the cellular uptake of drug-loaded microparticles were investigated. The drug-loaded microparticles exhibited sphere-like shape and small particle size with narrow particle size distribution. IDMC was amorphously dispersed within the PLLA/PLGA matrix after the SEDS process. In vitro release studies revealed that the drug-loaded microparticles substantially enhanced the dissolution rate of IDMC compared to the free IDMC, and demonstrated a biphasic drug release profile. In vitro cytotoxicity assays indicated that drug-loaded microparticles possessed longer sustained inhibition activity on proliferation of the non-small-cell lung cancer A549 cell lines than did free IDMC. Fluorescence microscopy and transmission electron microscopy identified the phagocytosis of drug-loaded microparticles into the A549 cells and characteristic morphology of cell apoptosis such as the nuclear aberrations, condensation of chromatin, and swelling damage in mitochondria. These results collectively suggested that IDMC-PLLA/PLGA microparticles prepared using SEDS would have potentials in anti-tumor applications as a controlled drug release dosage form without harmful organic solvent residue.
Kang
Yunqing
Y
College of Materials Science and Engineering, Sichuan University, #29 Wangjiang Road, Chengdu, PR China.
Wu
Jiang
J
Yin
Guangfu
G
Huang
Zhongbing
Z
Yao
Yadong
Y
Liao
Xiaoming
X
Chen
Aizheng
A
Pu
Ximing
X
Liao
Li
L
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D002245:Carbon Dioxide / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D025924:Chromatography, Supercritical Fluid; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006801:Humans; D007213:Indomethacin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry* / Q000633:toxicity; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D010316:Particle Size; D010587:Phagocytosis; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000633:toxicity; D033362:Powder Diffraction; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D012997:Solvents; D002245:Carbon Dioxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D007213:Indomethacin