Paclitaxel loaded PEGylated gleceryl monooleate based nanoparticulate carriers in chemotherapy.
A PEGylated drug delivery system of paclitaxel (PTX), based on glyceryl monooleate (GMO) was prepared by optimizing various parameters to explore its potential in anticancer therapy. The prepared system was characterized through polarized light microscopy, TEM, AFM and SAXS to reveal its liquid crystalline nature. As GMO based LCNPs exhibit high hemolytic toxicity and faster release of entrapped drug (66.2 ± 2.5% in 24 h), PEGylation strategy was utilized to increase the hemocompatibility (reduction in hemolysis from 60.3 ± 10.2 to 4.4 ± 1.3%) and control the release of PTX (43.6 ± 3.2% released in 24 h). The cytotoxic potential and cellular uptake was assessed in MCF-7 cell lines. Further, biodistribution studies were carried out in EAT (Ehrlich Ascites tumor) bearing mice using (99m)Tc-(Technetium radionuclide) labeled formulations and an enhanced circulation time and tumor accumulation (14 and 8 times, respectively) were observed with PEGylated carriers over plain ones, at 24 h. Finally, tumor growth inhibition experiment was performed and after 15 days, control group exhibited 15 times enhancement in tumor volume, while plain and PEGylated systems exhibited only 8 and 4 times enhancement, respectively, as compared to initial tumor volume. The results suggest that PEGylation enhances the hemocompatibility and efficacy of GMO based system that may serve as an efficient i.v. delivery vehicle for paclitaxel.
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr H S Gour University, Sagar, MP, India. jnarendr@yahoo.co.in
Vikas
V
Jain
Nitin K
NK
Swarnakar
Prabhat R
PR
Mishra
Ashwni
A
Verma
Ankur
A
Kaul
Anil K
AK
Mishra
Narendra K
NK
Jain
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D020285:Cryoelectron Microscopy / Q000379:methods; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D005989:Glycerides / Q000737:chemistry*; D006461:Hemolysis; D050866:Liquid Crystals; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods; D017239:Paclitaxel / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D051381:Rats; D012542:Scattering, Radiation; D013667:Technetium / Q000737:chemistry; D013997:Time Factors
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005989:Glycerides; D011092:Polyethylene Glycols; D013667:Technetium; C005953:monoolein; D017239:Paclitaxel