http://informahealthcare.com/ddi ISSN: 0363-9045 (print), 1520-5762 (electronic) Drug Dev Ind Pharm, Early Online: 1–10 ! 2015 Informa Healthcare USA, Inc. DOI: 10.3109/03639045.2014.1003220 RESEARCH ARTICLE Development of docetaxel nanocapsules for improving in vitro cytotoxicity and cellular uptake in MCF-7 cells Sandeep Kumar Singh*, Venkatesh Teja Banala*, Girish K. Gupta, Ashwni Verma, Rahul Shukla, Vivek K. Pawar, Priyanka Tripathi, and Prabhat Ranjan Mishra Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India. Abstract The aim of this study was to fabricate docetaxel loaded nanocapsules (DTX-NCs) with a high payload using Layer-by-Layer (LbL) technique by successive coating with alternate layers of oppositely charged polyelectrolytes. Developed nanocapsules (NCs) were characterized in terms of morphology, particle size distribution, zeta potential (z-potential), entrapment efficiency and in vitro release. The morphological characteristics of the NCs were assessed using transmission electron microscopy (TEM) that revealed coating of polyelectrolytes around the surface of particles. The developed NCs successfully attained a submicron particle size while the z-potential of optimized NCs alternated between (+) 34.64 ± 1.5 mV to () 33.25 ± 2.1 mV with each coating step. The non-hemolytic potential of the NCs indicated the suitability of the developed formulation for intravenous administration. A comparative study indicated that the cytotoxicity of positively charged NCs (F4) was significant higher (p50.05) rather than negative charged NCs (F3), plain drug (DTX) and marketed preparation (Taxotere Õ ) when evaluated in vitro on MCF-7 cells. Furthermore, cell uptake studies evidenced a higher uptake of positive NCs (1.2 fold) in comparison to negative NCs. In conclusion, formulated NCs are an ideal vehicle for passive targeting of drugs to tumor cells that may result in improved efficacy and reduced toxicity of encapsulated drug moiety. Keywords Cancer, cellular uptake, chitosan, controlled release, cytotoxicity, layer-by-layer, nanomedicine, sodium alginate History Received 30 June 2014 Revised 29 October 2014 Accepted 26 December 2014 Published online 17 February 2015 Introduction In the modern years, significant achievements have been witnessed in the field of drug delivery platform especially in the development of novel drug delivery systems (NDDS) such as nanocapsules (NCs), liposomes, polymeric nanoparticles and self- emulsifying delivery systems etc 1–3 . Layer-by-layer (LbL) tech- nique is one such an approach introduced in nineties, based on sequential adsorption of positively and negatively charged poly- electrolytes onto certain surface such as dissolvable colloidal particle, drug particle, dye and enzyme with nanothick film of coating to form NCs. The process involves resaturation of polyions adsorption resulting in the reversal of terminal charge of the film after deposition of each layer 4–7 . The use of NCs for the nanomedicine applications is a new and highly promising approach provides an exciting new drug delivery platform with promising clinical translational potential. A wide variety of polyelectrolytes (polycations and polyanions) including natural and biocompatible polymers can be utilized for the LbL nanoassembly. Formation of LbL polyelectrolyte NCs is a useful technique for controlled and targeted delivery of various drugs 4 . Micro- and nanoencapsulation by LbL assembly can offer many advantages, such as high drug payload efficiency, controlled release of drug at the infectious site, increased solubility, improved stability and minimizing side effects of the encapsulated drug 8–10 . The vast majority of studies concerning the LbL technique have used macroscopically flat charged surfaces as substrates for multilayer film formation 9 . Capsules prepared by means of the LbL technique have attracted particular interest, largely due to the ability readily to tailor their properties (e.g. size, composition, porosity, stability, surface functionality and colloidal stability), enabling control and triggered release of various therapeutic molecules by means of physicochemical triggers. All these attributes suggested that the LbL approach ensures high reproducibility and ease in industrial scale up of NCs. The fabricated capsules are particularly useful for delivery of proteins, enzymes, DNA and siRNA. Furthermore, use of a polyelectrolyte containing reactive groups (such as amino or carboxylic groups) for the last ‘‘outer’’ surface layer will allow for the attachment of specific ligands, or reporter groups, and other moieties of interest to nanocapsules 11 . Breast cancer is the most common adenocarcinoma in females with high incidence and mortality. Although early detection and screening is associated with less invasive surgical procedures, the 5-year survival rate of metastatic breast cancer (stage 4) is still below 15% 12,13 . Surgical removal remains the best method for locally controlled removal of the breast cancer tumors. Breast *Both the authors contributed equally. Address for correspondence: Prabhat Ranjan Mishra, Pharmaceutics Division, CSIR-Central Drug Research Institute, BS-10/1 Jankipuram Extension Sector-10, Sitapur Road, Lucknow-226031, Uttar Pradesh, India. CSIR-CDRI communication number 8883. Tel: +91 0522 2771940/ 2771942. Fax: +91 0522 2771960. 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