Pharmacokinetics and Biodistribution of Paclitaxel–Gelatin Nanoparticles

ABSTRACT

Nanoscale manipulation of properties of drug delivery systems (DDSs) provides improved control over the pharmacokinetics and pharmacodynamics of encapsulated drugs relative to free drugs. This article summarizes the preparation and therapeutic applications of paclitaxel–gelatin nanoparticles (PGNs) (Type B, 75 Bloom) in the size range ∼150 to 200 nm as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), with ∼45% entrapment efficiency. Dose-dependent antineoplasticity in hepatocarcinoma, HepG₂ cell line, was observed up to 72 h of incubation with PGN and the drug per se (<1 (g) showed 65% toxicity within 24 h).

A pharmacokinetics and biodistribution study with endpoints at 2, 6, 24, and 48 h performed in normal and tumor-bearing, inbred Balb-c mice showed accumulation in liver and tumor with PGN. Enhanced paclitaxel accumulation in kidney was observed. In vivo antineoplastic studies showed an approximately threefold reduction of tumor with PGN.

KEYWORDS:

• paclitaxel–gelatin nanoparticles
• DDS
• HepG₂
• pharmacokinetics
• biodistribution
• tumor regression

Acknowledgments

This work was supported by a Department of Biotechnology grant for NanoScience and Nano-Technology Research Initiative, Government of India (BT/PR/9895/NNT/28/55/2007). A.C. and R.P.P. are thankful to Department of Biotechnology (DBT) and Indian Council of Medical Research (ICMR) for their Senior Research Fellowship and R.V. and N.I. for their Junior Research Fellow (JRF). We are grateful to Dr. Rajni Rani, National Institute of Immunology, New Delhi, for providing the TEM facility.