INTERPENETRATING POLYMER NETWORK MICROSPHERES OF POLY (VINYL ALCOHOL)/METHYL CELLULOSE FOR CONTROLLED RELEASE STUDIES OF 6-THIOGUANINE
Abstract
Objective: The present study involved the preparation of Interpenetrating Polymer Network (IPN) microspheres formulated from Poly (vinyl alcohol) (PVA) and Methyl Cellulose (MC) for controlled release of an anti-cancer drug, 6-thioguanine.
Methods: The IPN microspheres were prepared by water-in-oil emulsion method using gluteraldehyde as a cross-linker. 6-thioguanine drug was successfully loaded into these microspheres via in-situ process. These prepared microspheres were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (X-RD), optical microscopy (OM) and Scanning electron microscopy (SEM).
Results: FTIR spectral data results confirmed the cross-linking reaction between IPN microspheres through gluteraldehyde. DSC and X-RD results indicated the molecular level distribution of 6-thioguanine drug in the polymer matrix. SEM images showed the microspheres have spherical shape with rough surface. OM results gave the average size of prepared microspheres that ranged from 40 to 280 µm. Encapsulation efficiency of the drug in these IPN microspheres was found to be 72 %. In vitro dissolution studies performed at pH 7.4 buffer medium showed that the drug release was depended on the extent of cross-linker, drug and the percentage of PVA used in the formulations. The drug release was analyzed by an empirical equation and was found to be non-Fickian type diffusion.
Conclusion: This study reveals that the combination of PVA and MC in the form of IPN microspheres may be used successfully for the controlled release of drugs with short plasma half-life. In vitro release studies showed the extended release of the drug for more than 12 h.
Keywords: Poly (vinyl alcohol), Methyl Cellulose, 6-thiogauanine, Interpenetrating Polymer Network Microspheres, In vitro release studies.
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Alavijeh MS, Chishty M, Qaiser MZ, Palmer AM. Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery. Neuro Rx 2005;2:554–71.
Phutane P, Shidhaye S, Lotlikar V, Ghule A, Sutar S, Kadam V. In vitro evaluation of novel sustained release microspheres of glipizide prepared by the emulsion solvent diffusion-evaporation method. J Young Pharm 2010;2:35–41.
Ray S, Banerjee S, Maiti S, Laha B, Barik S, Sa B, Bhattacharyya UK. Novel inter-penetrating network microspheres of xanthan gum-poly (vinyl alcohol) for the delivery of diclofenac sodium to the intestine – In vitro and in vivo evaluation. Drug Deliv 2010;17:508–19.
Halder A, Mukherjee S, Sa B. Development and evaluation of polyethyleneimine-treated calcium alginate beads for sustained release of dil-tiazem. J Microencapsul 2005;22:67–80.
Vijan V, Kaity S, Biswas S, Isaac J, Ghosh A. Microwave assisted synthesis and characterization of acrylamide grafted gellan, application in drug delivery. Carbohydr Polym 2012;90:496–506.
Vyas SP, Khar RK. Controlled drug delivery: concepts and advances. 1st ed. New Delhi: Vallabh Prakashan; 2002. p. 18–147.
Changez M, Burugapalli K, Koul V, Chowdary V. The effect of composi-tion of poly (acrylic acid) – gelatin hydrogel on gentamicin sulphate release: In vitro. Biomaterials 2003;24:527–36.
Krishna Rao KSV, Madhusudana Rao K, Nagendra Kumar PV, Chung II-D. Novel chitosan based pH sensitive micro-networks for the controlled release of 5-fluorouracil. Iranian Polymer J 2010;19:265-76.
Krishna Rao KSV, Subha MCS, Vijaya Kumar Naidu B, Sairam M, Mallikarjuna NN, Aminabhavi TM. Controlled release of diclofenac sodium and ibuprofen through beads of sodium alginate and hydroxy ethyl cellulose blends. J Appl Polym Sci 2006;102:5708-18.
Krishna Rao KSV, Naidu BVK, Subha MCS, Sairam M, Aminabhavi TM. Novel chitosan based pH-sensitive interpenetrating network microgels for the controlled release of cefadroxil. Carbohydr Polym 2006;66:333-44.
Prasad CV, Madhu Sudhan Rao K, Mallikarjuna B, Subha MCS, Chowdoji Rao K. Synthesis and characterization of SA-g-MAA co-polymer: effect of grafting and process variables on controlled release of an anti-bacterial drug. Adv Mat Res 2010;123:387-90.
Lakshmi Narayana Reddy C, Yerriswami B, Venkata Prasad C, Subha MCS, Chowdoji Rao K. Controlled release chlorpheniramine maleate through IPN beads of sodium alginate-g-methylmethacrylate. J Appl Polym Sci 2010;118:2342-49.
Yerri swamy B, Venkata Prasad C, Reddy CLN, Chowdoji Rao K, Subha MCS. Interpenetrating polymer network microspheres of hydroxy propyl methyl cellulose/poly (vinyl alcohol) for control release of ciprofloxacin hydrochloride. Cellulose 2011;18:349-57.
Tate MC, Shear DA, Hoffman SW, Stein DG, LaPlaca MC. Biocompatibility of methylcellulose-based constructs designed for intracerebral gelation following experimental traumatic brain injury. Biomaterials 2001;22:1113–23.
Gupta D, Tator CH, Shoichet MS. Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials 2006;27:2370–79.
Xu Y, Wang C, Tam KC, Li L. Salt-assisted and salt-suppressed sol–gel transitions of methylcellulose in water. Langmuir 2004;20:646–52.
Li L, Thangamathesvaran mp, Yue CY, Tam KC, Hu X, Lam YC. Gel network structure of methylcellulose in water. Langmuir 2001;17:8062–68.
Liang HF, Hong MH, Ho RM, Chung CK, Lin YH, Chen CH, et al. Novel method using a temperature-sensitive polymer (methylcellulose) to thermally gel aqueous alginate as a pH-sensitive hydrogel. Biomacromolecules 2004;5:1917–25.
Stabenfeldt SE, Garcia AJ, LaPlaca MC. Thermoreversible laminin-functionalized hydrogel for neural tissue engineering. J Biomed Mater Res A 2006;77:718–25.
Horiike S, Matsuzawa S, Yamaura K. Preparation of chemically crosslinked gels with maleate-denatured poly (vinyl alcohol) and its application to drug release. J Appl Polym Sci 2002;84:1178-84.
Sreenivasan K. Absorption characteristics of a novel semi-IPN membrane based on β-cyclodextrin toward testosterone and progesterone. J Appl Polym Sci 1997;64:1811-14.
Orienti I, Trere R, Luppi B, Bigucci F, Cerchiara T, Uccari G, Zecchi V. Hydrogels Formed by Crosslinked Poly(vinyl alcohol) as Sustained Drug Delivery Systems. Arch Pharm 1999;335:89-93.
Kweon DK, Kang DW. Drug-release behavior of chitosan-g-poly(vinyl alcohol) copolymer matrix. J Appl Polym Sci 1999;74:458-64.
Feng X, Huang RYM. Preparation and performance of asymmetric polyetherimide membranes for isopropanol dehydration by pervaporation. J Memb Sci 1996;109:165-72.
Lee KH, Kim HK, Rhim JW. Pervaporation separation of binary organic–aqueous liquid mixtures using crosslinked PVA membranes. III Ethanol–water mixtures. J Appl Polym Sci 2003;58:1707-12.
Huang RYM, Yeom CK. Development of crosslinked poly (vinyl alcohol) (type II) and permeation of acetic acid—water mixtures. J Memb Sci 1991;62:59-73.
Isiklan N, Sanli O. Permeation and separation characteristics of acetic acid/water mixtures through poly (vinyl alcohol-g-itaconic acid) membranes by pervaporation, evapomeation, and temperature-difference evapomeation. J Appl Polym Sci 2004;93:2322-33.
Isiklan N, Sanli O. Separation characteristics of acetic acid-water mixtures by pervaporation using poly (vinyl alcohol) membranes modified with malic acid. Chem Engineering Processing: Pro Intensification 2005;44:1019-27.
Sanli O, Asman G. Release of diclofenac through gluteraldehyde crosslinked poly (vinyl alcohol)/poly (acrylic acid) alloy membranes. J Appl Polym Sci 2003;91:72-77.
Vora A, Mitchell CD, Lennard L, Eden TO, Kinsey SE, Lilleyman J, Richards SM. Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia: a randomised trial. Lancet 2006;368:1339-48.
Madhusudana Rao K, Mallikarjuna B, Krishna Rao KSV, Prabhakar MN, Chowdoji Rao K, Subha MCS. Preparation and characterization of pH sensitive poly (vinyl alcohol)/sodium carboxymethyl cellulose IPN microspheres for In vitro release studies of an anti-cancer drug. Polym Bull 2012;68:1905-19.
Gunasekaran, Kumaresan S, Arun balaji R, Anand G, Seshadri. Vibrational spectra and normal coordinate analysis on structure of chlorambucil and thioguanine. Pramana 2008;71:1291-300.
Ritger PL, Peppas NA. A simple equation for description of solute release. II Fickian and anomalous release from swellable devices. J Cont Rel 1987;5:37-42.
Lyu SP, Sparer R, Hobot C, Dang K. Adjusting drug diffusivity using miscible polymer blends. J Cont Rel 2005;102:679-87.