Localized delivery of paclitaxel in solid tumors from biodegradable chitin microparticle formulations.
Paclitaxel (Taxol)-containing chitin and chitin-Pluronic F-108 microparticles were formulated as biodegradable systems for localized administration in solid tumors. The microparticles were characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), and swelling studies in phosphate-buffered saline (PBS, pH 7.4). Lysozyme-induced degradation and in vitro release of paclitaxel was examined in PBS at 37 degrees C. The percent change in tumor volume was used to assess efficacy of the Formulations after local administration in murine Lewis lung carcinoma model. FT-IR confirmed higher degree of acetylation in chitin microparticles from the starting chitosan sample and the SEM showed that the chitin-Pluronic F-108 microparticles were significantly more porous than chitin microparticles. Due to higher porosity, chitin-Pluronic microparticles were able to imbibe higher swelling medium and degraded much faster in the presence of lysozyme than chitin microparticles. After 48 h. 51% of incorporated paclitaxel was released from chitin-Pluronic microparticles as compared to 28% from chitin microparticles. In vivo studies in Lewis lung carcinoma-bearing mice showed that the tumor volumes after 6 days using paclitaxel-loaded chitin and chitin-Pluronic F-108 microparticles was 458 and 307 mm3, respectively. In contrast, the tumor volume was 997 mm3 for the untreated control. The results of this study show that chitin and chitin-Pluronic F-108 microparticles are biodegradable drug delivery systems that can be useful for localized delivery of paclitaxel in solid tumors.
Nsereko
Sarah
S
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02115, USA.
Amiji
Mansoor
M
D000117:Acetylglucosamine / Q000737:chemistry; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry*; D001673:Biodegradation, Environmental; D002686:Chitin / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009113:Muramidase / Q000378:metabolism; D009369:Neoplasms / Q000628:therapy; D009374:Neoplasms, Experimental; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D020442:Poloxamer / Q000494:pharmacology; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D013501:Surface-Active Agents; D020442:Poloxamer; D002686:Chitin; D009113:Muramidase; D017239:Paclitaxel; D000117:Acetylglucosamine