Hydrogel matrix entrapping PLGA-paclitaxel microspheres: drug delivery with near zero-order release and implantability advantages for malignant brain tumour chemotherapy.
OBJECTIVE
To develop paclitaxel-delivering PLGA microspheres entrapped in a gel matrix with sustained drug release properties and implantability advantages for local glioma chemotherapy.


METHODS
Paclitaxel-loaded PLGA microspheres were fabricated using electrohydrodynamic atomization and entrapped by electrospray and gelation. The physicochemical characterizations were performed using scanning electron microscopy and differential scanning calorimetry. The influence of various parameters on the disintegration time was investigated. In vitro release of paclitaxel was quantified using high performance liquid chromatography. Cytotoxicity of the formulations was assessed by the quantification of IC(50) and caspase-3 activity against C6 glioma cells in vitro. The formulations were tested against a subcutaneous C6 glioma tumour in mice.


RESULTS
Highly monodisperse gel beads containing a uniform microsphere distribution were obtained. Gelation using Ca(2+) ions ensured entrapment of microspheres with high loading efficiency. With an increase in the gelation time, gelling bath concentration and decrease in microsphere loading, it was more difficult to disintegrate the beads and release the microspheres. The formulations demonstrated sustained drug release for more than 60 days at a near-constant rate and a low initial burst. Cell culture studies proved the cytotoxicity against C6 glioma and improved performance in comparison to Taxol. The formulations could reduce subcutaneous tumour volume to a greater extent compared to Taxol and the control.


CONCLUSIONS
Paclitaxel-loaded PLGA microspheres entrapped in an alginate gel matrix could be potential local chemotherapy implants to treat malignant glioma with critical advantages of implantability and sustained drug release with low initial burst.
Ranganath
Sudhir Hulikal
SH
Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore.
Kee
Irene
I
Krantz
William B
WB
Chow
Pierce Kah-Hoe
PK
Wang
Chi-Hwa
CH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000627:therapeutic use; D017209:Apoptosis; D001932:Brain Neoplasms / Q000188:drug therapy*; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D020100:Hydrogels; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D017239:Paclitaxel / Q000737:chemistry* / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats
D000972:Antineoplastic Agents, Phytogenic; D020100:Hydrogels; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel