Colloids and Surfaces B: Biointerfaces 162 (2018) 25–34 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces j o ur nal ho me pa ge: www.elsevier.com/locate/colsurfb Full Length Article In vitro and in vivo evaluation of 10-hydroxycamptothecin-loaded poly (n-butyl cyanoacrylate) nanoparticles prepared by miniemulsion polymerization Xin Jin a , Sajid Asghar b , Xieting Zhu a , Zhipeng Chen c , Cihui Tian a , Lining Yin a , Qineng Ping a , Yanyu Xiao a,∗ a Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China b Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan c Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China a r t i c l e i n f o Article history: Received 5 August 2017 Received in revised form 25 September 2017 Accepted 10 November 2017 Available online 12 November 2017 Keywords: 10-Hydroxycamptothecin n-Butyl cyanoacrylate Miniemulsion polymerisation Oral bioavailability Pharmacokinetics a b s t r a c t In this paper, 10-hydroxycamptothecin (HCPT)-loaded poly (n-butyl cyanoacrylate) nanoparticles (HCPT- PBCA-NPs) co-modified with polysorbate 80, soybean phospholipids, and polyethylene glycol (100) monostearate were successfully prepared via miniemulsion polymerization, and were characterized for particle size, morphology, zeta potential, encapsulation efficiency (EE) and drug loading capacity (DL). The chemical structure of HCPT-PBCA-NPs and the state of HCPT in the PBCA-NPs were investigated by DSC, FTIR and 1 H NMR. Additionally, drug release, cytotoxicity, cellular uptake capacity, cellular uptake mechanism, and in vivo behavior of NPs were investigated as well. The particles were 92.7 nm in size with a high EE of 94.24%. FTIR, 1 H NMR, and DSC demonstrated complete polymerization of BCA monomers and the drug was in a molecular or amorphous form inside the NPs. In vitro release of the drug from HCPT- PBCA-NPs exhibited sustained-release and less than 60% of HCPT was released from the NPs within 24 h of dialysis. Cellular uptake study displayed that Caco-2 cell uptake of NPs was governed by active endocy- tosis, clathrin- and caveolin-mediated process, and increased with the increase of the NPs concentration and the time. The pharmacokinetic study in rats showed that encapsulation of HCPT into PBCA-NPs increased the C max and AUC 0−t about 6.52 and 7.56 times, respectively, in comparison with the HCPT sus- pension. It was concluded that HCPT loaded PBCA-NPs prepared by miniemulsion polymerization could be promising in oral drug delivery. © 2017 Elsevier B.V. All rights reserved. 1. Introduction 10-Hydroxycamptothecin (HCPT) is a promising antitumor agent with a broad spectrum of antitumor activities, targets nuclear enzyme topoisomerase I (topo I) to inhibit DNA replication and RNA transcription [1]. It has shown significant antitumor activity against various tumors including bladder cancer, gastric carcinoma, hepatoma, colorectal cancer, and tumor of head and neck [2–4]. However, the oral delivery of HCPT is limited due to its poor stability, permeability and solubility in water and physiologically acceptable solvents [5,6]. In the past few years, many attempts have been made to develop high-performance oral delivery systems for ∗ Corresponding author at: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tong Jia Xiang, Nanjing 210009, PR China. E-mail address: cpuyanyuxiao@163.com (Y. Xiao). HCPT, such as microspheres [7], microcapsules [8], nanosuspen- sions [9] and polymeric nanoparticles [10]. Polymeric nanoparticles have attracted considerable attention as one of the promising oral delivery systems to improve the bioavailability of hydrophobic drugs [11,12]. Among various poly- meric materials, poly (n-butyl cyanoacrylate) (PBCA) has been widely used as a drug carrier and it also meets the require- ments for oral drug delivery such as excellent biocompatibility and biodegradability. Preparation of PBCA nanoparticles is mainly achieved by two modes, anionic polymerization and radical poly- merization. Anionic polymerization is of wide application owing to simple polymerization process and mild reaction conditions [13], including emulsion polymerization [14], interfacial polymerization [15] and miniemulsion polymerization methods [16]. In our previ- ous study [17], we have successfully prepared HCPT-loaded poly (n-butyl cyanoacrylate) nanospheres (HCPT-PBCA-NSs) via emul- sion polymerization of BCA monomers in acidic medium with the https://doi.org/10.1016/j.colsurfb.2017.11.029 0927-7765/© 2017 Elsevier B.V. All rights reserved.