5-Florouracil-loaded poly(lactic acid)-poly(caprolactone) hybrid scaffold: Potential chemotherapeutic implant Kamal K. Gupta, 1 Namrata Pal, 1 Pradeep K. Mishra, 1 Pradeep Srivastava, 2 Sujata Mohanty, 3 Pralay Maiti 4 1 Department of Chemical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, India 2 School of Biochemical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, India 3 Stem Cell Facility, All India Institute of Medical Sciences, New Delhi 110029, India 4 School of Material Science and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, India Received 2 July 2013; revised 12 August 2013; accepted 19 August 2013 Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.34932 Abstract: Hybrid nanofibers of poly(lactic acid) and polycap- rolactone have been developed by embedding cancerous drug through electrospinning technique. The composition of polymer has been varied to check the compositional effect on properties. The quality of nanofibers has been testified through surface morphology, wetting properties using con- tact angle and mechanical strength under uniaxial elongation. The compatibility of drug (5-fluorourasil) with matrix fiber has been verified using Fourier transform infrared, X-ray dif- fraction, Raman spectroscopy, and differential scanning calo- rimetry. The drug release study has been performed showing greater release in hybrid fibers when compared with pure polymers as a result of synergism of two immiscible poly- mers and quasi-Fickian diffusion mechanism in hybrid nano- fiber as implants showing compositional effect on drug release. A model has been proposed showing faster release of drugs in hybrid systems. Biological responses through flu- orescence imaging and MTT assay confirm the release of drug from hybrid nanofibers showing potential use of hybrid scaffolds as chemotherapeutic implant. V C 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 00A:000–000, 2013. Key Words: poly(lactic acid), polycaprolactone, 5-florouracil, hybrid, nanofibers, osteoblast cell How to cite this article: Gupta KK, Pal N, Mishra PK, Srivastava P, Mohanty S, Maiti P. 2013. 5-Florouracil-loaded poly(lactic acid)- poly(caprolactone) hybrid scaffold: Potential chemotherapeutic implant. J Biomed Mater Res Part A 2013: 00A: 000–000. INTRODUCTION Cancer is an enormous health concern and predominant cause of death worldwide during last few decades. Nanoma- terials have unique properties of higher surface area to vol- ume ratio, nanotechnology may be a new path for cancer treatments. 1 Polymeric three dimensional structured materi- als as drug carriers allow the continuous and controlled localized therapeutic drugs release with a desired limit, spe- cifically targeting the drugs to their intended infected tis- sues and cells to reduce drug doses for improving patient compliance and cure. In the literature, polymeric cancer treatment/chemotherapeutic materials (film, micro or nano- particles, nanofibers, and hydrogels) are developed by researcher using anticancerous drug/chemotherapic agents like 5-florouracil, 2–7 paclitaxel, 8 doxorubicin and doxorubicin hydrochloride, 9,10 daunorubicin, 11 1,3-bis(2-chloroethyl)-1- nitrosourea (BCNU), 12 camptothecin, 1 methotrexate, 13 doce- taxel, 14 and gemcitabine. 15 5-Fluorouracil (5-FU) is a well- known antimetabolite water soluble drug used as treatment of solid tumors of childhood and adult cancer patients. It exerts its anticancer effect through inhibiting the nucleotide synthetic enzyme, thymidylate synthase, that is necessary for incorporation of its metabolites into RNA and DNA repli- cation and repair causing the arrest of cancer cell division cycle and even apoptosis and proliferative inhibition of nor- mal cells. 3 Drug released form biodegradable polymeric system depends on the physical and chemical properties (molecular weight, crystalline state, hydrophilicity, and degradation rate of drug carrier) of polymer, environment, nature of drug (hydrophilic/hydrophobic), structure and porosity of the matrix polymer. 4,16 There are many reports of biodegradable polymers, e.g., poly(lactic acid) (PLA), poly(caprolactone) (PCL), poly(ethylene glycol) (PEG), poly(lactide-co-glycolide) (PLGA), 2,8,16,17 and chitosan 18,19 for drug delivery matrix. Considering the interaction of drug and polymer and tuna- ble/sustained drug release form the carrier, selection of polymer matrix is very important during designing of drug delivery implants/carriers. Drug release in the implant can also be tuned by blending of different molecular weight of Additional Supporting Information may be found in the online version of this article. Correspondence to: P. Maiti; e-mail: pmaiti.mst@itbhu.ac.in Contract grant sponsor: University Grant Commission (UGC) V C 2013 WILEY PERIODICALS, INC. 1