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PLGA Nanoparticles Stabilized with Cationic Surfactant: Safety Studies and Application in Oral Delivery of Paclitaxel to Treat Chemical-Induced Breast Cancer in Rat

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Abstract

Purpose

This study was carried out to formulate poly(lactide-co-glycolide) (PLGA) nanoparticles using a quaternary ammonium salt didodecyl dimethylammonium bromide (DMAB) and checking their utility to deliver paclitaxel by oral route.

Methods

Particles were prepared by emulsion solvent diffusion evaporation method. DMAB and particles stabilized with it were evaluated by MTT and LDH cytotoxicity assays. Paclitaxel was encapsulated in these nanoparticles and evaluated in a chemical carcinogenesis model in Sprague Dawley rats.

Results

MTT and LDH assays showed the surfactant to be safe to in vitro cell cultures at concentrations <33 μM. PLGA nanoparticles prepared using this stabilizer were also found to be non-toxic to cell lines for the duration of the study. When administered orally to rats bearing chemically induced breast cancer, nanoparticles were equally effective/better than intravenous paclitaxel in cremophor EL at 50% lower dose.

Conclusions

This study proves the safety and utility of DMAB in stabilizing preformed polymers like PLGA resulting in nanoparticles. This preliminary data provides a proof of concept of enabling oral chemotherapy by efficacy enhancement for paclitaxel.

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ACKNOWLEDGMENTS

V. Bhardwaj is grateful for the financial support of a Galenos Fellowship in the Framework of the EU Project “Towards a European PhD in Advanced Drug Delivery,” Marie Curie Contract MEST-CT-2004-404992. The partial in vitro and in vivo work presented here is conducted at NIPER and authors thank Director NIPER for extending the facility. Financial support (No. IR/SO/LF-03/2006) from Department of Science and Technology (DST), Govt. of India is acknowledged.

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Correspondence to M. N. V. Ravi Kumar.

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Bhardwaj, V., Ankola, D.D., Gupta, S.C. et al. PLGA Nanoparticles Stabilized with Cationic Surfactant: Safety Studies and Application in Oral Delivery of Paclitaxel to Treat Chemical-Induced Breast Cancer in Rat. Pharm Res 26, 2495–2503 (2009). https://doi.org/10.1007/s11095-009-9965-4

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