Colloids and Surfaces B: Biointerfaces 112 (2013) 400–407 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces jou rn al hom epage: www.elsevier.com/locate/colsurfb Evaluation of clay/poly (l-lactide) microcomposites as anticancer drug, 6-mercaptopurine reservoir through in vitro cytotoxicity, oxidative stress markers and in vivo pharmacokinetics Bhavesh D. Kevadiya a,c,2 , Shiva Shankaran Chettiar b,1 , Shalini Rajkumar c,2 , Hari C. Bajaj a,∗ , Kalpeshgiri A. Gosai a , Harshad Brahmbhatt a a Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Council of Scientific and Industrial Research (CSIR), Gijubhai Badheka Marg, Bhavnagar 364 002, Gujarat, India b Department of Biotechnology, Shree Ramkrishna Institute of Computer Education and Applied Sciences, Veer Narmad South Gujarat University, Surat, India c Institute of Science, Nirma University, Ahmedabad 382481, Gujarat, India a r t i c l e i n f o Article history: Received 7 February 2013 Received in revised form 5 June 2013 Accepted 3 July 2013 Available online xxx Keywords: Na + -clay Cytotoxicity 6-Mercaptopurine Oxidative stress Neuroblastoma a b s t r a c t Intercalation of 6-mercaptopurine (6-MP), an antineoplastic drug in interlayer gallery of Na + -clay (MMT) was further entrapped in poly (l-lactide) matrix to form microcomposite spheres (MPs) in order to reduce the cell toxicity and enhance in vitro release and pharmacokinetic proficiency. The drug–clay hybrid was fabricated via intercalation by ion-exchange method to form MPs from hybrid. In vitro drug release showed controlled pattern, fitted to kinetic models suggested controlled exchange and partial diffusion through swollen matrix of clay inter layered gallery. The in vitro efficacy of formulated composites drug was tested in Human neuroblastoma cell line (IMR32) by various cell cytotoxic and oxidative stress marker indices. In vivo pharmacokinetics suggested that the intensity of formulated drug level in plasma was within remedial borders as compared to free drug. These clay based composites therefore have great potential of becoming a new dosage form of 6-MP. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Since 1950s, 6-MP has been used to cure human leukemia and many other diseases such as inflammation of colon and small intestine e.g. Crohn’s disease and ulcerative colitis, systemic autoimmune disease and rheumatoid arthritis [1–4]. It has been established that 6-MP and its metabolites exert their primary cyto- toxicity through incorporation of deoxythioguanosine into DNA throughout anabolism pathway and inhibit the function of RANase- H in DNA–RNA heteroduplex molecules [5]. The drug is water insoluble and the free sulfhydryl group can easily form a disulfide bond with the plasma protein. The drug has a short plasma half-life (0.5–1.5 h) and lower bioavailability (about 16%) and plummeting chemotherapeutic effect [6,7]. Drug carriers proficient of sustained release with low toxicity are urgently required for providing and maintaining desired concentration of drug without letting it reach ∗ Corresponding author. Tel.: +91 278 2471793; fax: +91 278 2567562. E-mail addresses: scheti@gmail.com (S.S. Chettiar), shalini.rjk@nirmauni.ac.in (S. Rajkumar), hcbajaj@csmcri.org (H.C. Bajaj). 1 Tel.: +91 0261 2240172; fax: +91 0261 2240170. 2 Tel.: +91 2717 241900–04, 241911–15; fax: +91 2717 241916x17. a higher toxic level or drop below the least efficient level for long period [8–15]. In order to address these issues, carriers such as lipo- somes, cement, dendrimers and nanoparticles have been typically explored, as they represent excellent carriers for the integration of hydrophobic 6-MP [3,16–19] but several limitations, such as expen- sive or conservative synthesis procedure, lack of bioavailability and biodegradation with precursor material toxicity. One of the possible approaches for overcoming these disad- vantages and improving the oral chemotherapeutic activity, the layered silicate material is used as drug carriers. During the last decade, incorporation of anticancer drugs into a variety of lay- ered silicate materials as carriers is gaining popularity for the preparation of controlled release dosage forms [8–11]. MMT (mont- morillonite) is one of the most commonly used medical clay that consists of a lamellar stack of crystalline, 1 nm thick aluminosili- cate sheets. Its crystalline lattice consists of an aluminum–oxygen and aluminumhydroxyl octahedral sheet sandwiched by two silicon–oxygen tetrahedral sheets [10–15]. Naturally occurring cation (i.e., Na + ) reside between the sheets to balance the over- all negative surface charge of MMT. In water, the lamellar stack swells to an electrostatically stabilized dispersion of nanoscale sheets. MMT has swelling capability by the stepwise hydration of the interlayer cations and intercalation with positively charged 0927-7765/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.colsurfb.2013.07.008