Nanolipid carrier-based thermoreversible gel for localized delivery of docetaxel to breast cancer

Tanya Vohra,Hemraj Heer,Inderpreet Kaur,Rayasa Ramachandra Murthy

doi:10.1007/s12645-013-0032-9

Tanya Vohra, Hemraj Heer + Show 2 more

Open Access

https://doi.org/10.1007/s12645-013-0032-9

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Abstract

Intratumoral and intralesional administration of anticancer drugs in gels and implantable formulations is gaining much importance on account of its advantage of site-specific delivery with highly dependable freedom from unwanted side effects. Nanolipid carriers (NLC) are the preferred vehicle due to their improved properties particularly drug loading. In the present investigation, glyceryl monostearate–oleic acid NLCs loaded with docetaxel were prepared by emulsification and ultrasonication technique and were incorporated in thermoreversible pluronic F127 gel (TRPgel) for intralesion injection to breast tissue. The NLCs were spherical particles of 113 nm size with a negative zeta potential of −32.8 and 85 % drug entrapment. In vitro drug release profile of the NLC showed 96 % drug release in 48 h following Higuchi release kinetics. NLC incorporated TRPgel showed mucoadhesive force of 3.07 dynes/cm2 and gelling temperature in the range of 32 to 37 °C. The drug entrapped gel was also subjected to in vitro cytotoxicity study in human B-16 and HeLa cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and in vivo drug distribution study in breast tissue in healthy Wistar rats. The MTT assay revealed that docetaxel-loaded NLC incorporated into gel showed lower cytotoxicity than docetaxel. However, in vivo breast tissue distribution studies showed high tissue drug concentration, sustained over a period of 60 h in comparison to docetaxel and docetaxel-loaded NLCs. These results suggest that nanolipid carrier of docetaxel in TRPgel could be a promising carrier system to deliver drug to tumor by intralesional administration for improving therapeutic benefits of docetaxel.

Highlights

Breast cancer accounts for 33 % of all incident cancers in women, with an increasing mortality rate in North America (Jemal et al 2005)
The parameters such as homogenization time, sonication time, weight ratio of drug to lipids, weight ratio of solid lipids to liquid lipids, and the concentration of pluronic F127 were optimized each at various levels taking the particle size, polydispersity index (PDI), zeta potential, Table 3 Optimization parameters of gel
3.1.2 Nanolipid carrier in gel Various parameters were optimized like polymer concentration which affects the diffusivity of drug in higher polymer concentration (like 20 %, 22 % (w/w)) in formulation of pluronic F127 gel

Summary

Introduction

Breast cancer accounts for 33 % of all incident cancers in women, with an increasing mortality rate in North America (Jemal et al 2005). Most cytotoxic agents when administered systemically into cancer patients provide various limitations and challenges These limitations include large volume of distribution leading to systemic toxicity of vital organs, low blood flow into interior of a tumor site resulting in inability to provide optimal dose, and frequent dose reduction due to various toxicities like hematologic, neurologic, and physiological. For these reasons, drug delivery technology research has focused on targeting anticancer drugs to a specific site or to develop intratumoral or intralesional injections to provide timed release profile for better management and cure of cancer (Rob et al 2006)

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