International Journal of Biological Macromolecules 72 (2015) 309–319 Contents lists available at ScienceDirect International Journal of Biological Macromolecules j ourna l h o mepa ge: www.elsevier.com/locate/ijbiomac Therapeutic efficacy and toxicity of tamoxifen loaded PLA nanoparticles for breast cancer Sanjeev K. Pandey a , Somenath Ghosh a , Pralay Maiti b , Chandana Haldar a,∗ a Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi 221 005, India b School of Materials Science and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi 221 005, India a r t i c l e i n f o Article history: Received 4 June 2014 Received in revised form 4 August 2014 Accepted 14 August 2014 Available online 23 August 2014 Keywords: Tamoxifen Nanoparticles Emulsification nanoprecipitation a b s t r a c t This study was carried out to assess the therapeutic efficacy and toxicity of tamoxifen (Tmx) loaded poly(d,l-lactic acid) (PLA) nanoparticles (Tmx-NPs) for breast cancer. An in vivo study was conducted to determine the effect of Tmx-NPs on DMBA induced mammary tumor in female Wistar rat. The experimen- tal results showed that the mean diameter of Tmx-NPs was 224 ± 3 nm with 68 ± 2% (w/w) of entrapment efficiency. In in vivo study, the tumor size in rat was significantly reduced (P < 0.001) by treating Tmx-NPs as compared to pure Tmx and untreated group (control DMBA). Tmx-NPs showed the marked reduc- tion in hepatotoxicity and renal toxicity when compared to pure Tmx as evidenced by histopathological examination of liver and kidney tissues as well as estimation of AST, ALT levels, and creatinine, urea, blood urea nitrogen levels. Oxidative stress and lipid peroxidation was estimated in spleen, liver and kidney and was found significantly high in pure Tmx treated group as compared to Tmx-NPs and control group. Immunological parameters like blastogenic response of splenocytes, TLC, DLC were studied and found significantly high in pure Tmx treated group but the variations were nonsignificant in Tmx-NPs group as compared to control. Thus, Tmx-NPs have significant therapeutic efficacy with reduced side effects. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Breast cancer is a major health problem worldwide and is second leading cause of cancer death especially for women. Chemother- apy is a very complicated and high risk procedure due to its toxicity. Patients tolerate severe side effects even after success- ful chemotherapy [1,2]. One of the major problems of cancer chemotherapy is to administer the required therapeutic concentra- tion of drug at the tumor site for the desired period of time without causing undesirable effects on other organs [3,4]. Tamoxifen is an estrogen receptor modulator [5] that exhibits good bioavailabil- ity upon oral administration [6]. Following long term therapy of tamoxifen causes major side effects. To overcome the undesirable side effects of tamoxifen and increase the concentration at the tumor site, tamoxifen has been entrapped in various polymeric nanoparticles to improve better delivery by increasing local con- centration of the drug at the receptor site [7,8]. Various anticancer drugs have been entrapped in various polymeric nanoparticles ∗ Corresponding author. Tel.: +91 542 2307149x125; fax: +91 542 2368174/2575093. E-mail addresses: sanjeevbiochem11@gmail.com (S.K. Pandey), chaldar2001@yahoo.com (C. Haldar). to enhance their activity by reducing side effects [9–11]. Vari- ous biodegradable polymeric nanoparticles have been extensively used for controlled delivery of active molecules and drugs [12–16]. The polymeric nanoparticles have the potential to act as a car- rier of drugs at target sites by enhancing the biological activity and reducing the adverse side effects [17,18]. Various biodegrad- able polymers such as poly(lactic-co-glycolic acid) (PLGA), poly (d,l-lactic acid) (PLA), poly(-caprolactone) (PCL), chitosan, gelatin and poly(alkyl cyanoacrylates) have been extensively used as poly- meric nanoparticles for targeted delivery of drugs related to cancer, diabetes, malaria and other harmful diseases [19–23]. Among them, PLA has been also approved by Food and Drug Adminis- tration (FDA) for the clinical uses as a carrier of drug delivery processes [24]. During this process, when polymeric nanoparti- cles are administered orally, the M-cells (specialized cells staying over mucosa-associated lymphoid tissue) in payer’s patches uptake the nanoparticles and transport them from the gut lumen to intra- epithelial lymphoid cells and then through the lymphatic system into the blood stream [25–27]. Polymeric nanoparticles follow this particular way and thus improve the bioavailability of encapsulated drug by avoiding the enzymatic degradation in enterocytes. In the present study, tamoxifen loaded PLA nanoparticles (Tmx-NPs) have been developed, optimized and characterized. The dried Tmx-NPs have been explored for in vitro release characteristics and in vivo http://dx.doi.org/10.1016/j.ijbiomac.2014.08.012 0141-8130/© 2014 Elsevier B.V. All rights reserved.