Abstract
Progress in nanoscience and nanotechnology laid foundation for nanotherapy-based approach in cancer drug delivery for improved therapy and quality of life. The prepared polymeric nanoparticles (PNPs), PCL, PLGA and PLA NPs help in delivering paclitaxel (TAX) in vivo by avoiding the use of unsafe excipient, Cremophore EL. The classy microscopic examination SEM, TEM and AFM analysis revealed the spherical and smooth structure of the NPs as well as their homogeneous solid matrix without any amorphous arrangements. The FTIR analysis of PNPs exposed that there was no chemical interaction between polymer, stabilizer and TAX. The 1H NMR and XRD analyses illustrate molecular dispersion of TAX in the polymeric matrix and no evidence was observed for the presence of crystalline TAX. The outcome of in vivo acute toxicity study endorses residual solvent free PNPs. The PNPs demonstrate excellent control in delivering TAX up to 48 h with best fitted to First-order, Baker-Lonsdale, Higuchi and Korsmeyer-Peppas model. The log plasma concentration–time profile shows that the prepared PNPs were safe and have much less side-effects. The pharmacokinetic study results illustrate increase in mean residence time as result of long circulating nature of the prepared nanoparticles, which helps them to reach target area. The estimated pharmacokinetic parameters AUC0–∞ (ng h)/mL, AUMC0–∞ (ng h2)/mL, C max (ng/mL), t 1/2 (h), MRT (h), Cl (L/h/kg), V ss (L/kg) and V z (L/kg) shows improved therapeutic efficacy when compared with TAX solution.
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Acknowledgments
One of the authors, Sekar VasanthaKumar (SVK) acknowledges Council of Scientific and Industrial Research (CSIR, New Delhi, India) for providing scholarship, Senior Research Fellow (SRF). Authors are grateful to Getwell Pharmaceuticals (New Delhi, India) for generous gift samples of TAX. Authors appreciate the services provided by Central Electronics Engineering Research Institute (Rajasthan, India) and Sophisticated Analytical Instrument Facility, Indian Institute of Technology (Mumbai, India) to analyze our samples by Scanning Electron Microscopy, Atomic Force Microscopy and Transmission Electron Microscopy and Nuclear Magnetic Resonances. Last but not least, author SVK appreciates Dr. P SenthilKumar, Assistant Professor, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, India for his help during literature review.
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Sekar VasanthaKumar made substantial contribution to conception and design of the entire research work. He was involved in conducting all the experiments and obtaining data. He contributed significantly in analyzing and interpreting the obtained data. He was involved in making the draft manuscript and critically reviewing the draft. Ranendra N. Saha equally made substantial contribution to conception and design of the entire research work. He critically reviewed the draft manuscript and gave final approval of the version to be submitted. Haja Nazeer Ahamed helped in conception and design of in vivo acute toxicity study. He also contributed in analyzing and interpreting of the toxicity study result.
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VasanthaKumar, S., Ahamed, H.N. & Saha, R.N. Nanomedicine I: In vitro and in vivo evaluation of paclitaxel loaded poly-(ε-caprolactone), poly (dl-lactide-co-glycolide) and poly (dl-lactic acid) matrix nanoparticles in wistar rats. Eur J Drug Metab Pharmacokinet 40, 137–161 (2015). https://doi.org/10.1007/s13318-014-0189-6
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DOI: https://doi.org/10.1007/s13318-014-0189-6