Poly (Ethylene Glycol) / Gelatin Composite Hydrogels for Drug Delivery
DOI:
https://doi.org/10.12974/2311-8717.2014.02.01.5Keywords:
Poly(ethylene glycol)-diacrylate (PEG-DA), Gelatin, Composite hydrogel, Photopolymerization, Drug delivery, Gentamicin.Abstract
Hydrogels are three dimentional, hydrophilic, and polymeric networks that have been designed and fabricated to fulfill the needs of the pharmaceutical and medical fields. Many biomedical applications including controlled drug delivery have developed based on hydrogel technologies. Various composite hydrogels including synthetic and natural materials can be produced to create controllable systems in drug delivery applications. In this study, poly(ethylene glycol) (PEG-DA) based composite hydrogels were prepared by photopolymerization method and 2,2-dimethoxy-2-phenylacetophenone (DMPA) was used as photoinitiator. Macromer mixtures were prepared by mixing 30 % PEG-DA and 0.5 % DMPA. Photocuring was achieved by cross-linking with 3 % ethylene glycol diacrylate (EGDMA) after addition of drug and gelatin solutions under mild conditions. The effect of gelatin concentration and molecular weight on the gentamicin release was studied with 75, 100, 225, and 300 bloom gelatin for 0.1, 0.5, and 1.0 w/w ratios. Drug release kinetics from loaded composite hydrogels were tested by spectrophotometric method in phosphate (pH 7.4) and citrate buffer (pH 1.2) representing small intestine and stomach media, respectively. New biopolymer containing composite hydrogels enhanced drug release rates for all compositions and gentamicin release was found to be adversely effected by concentration and molecular weight. Hydrogels were morphologically characterized by SEM images which indicated the presence of pinholes like structures with smaller sizes for larger molecular weights.
References
Hoffman AS. Hydrogels for biomedical applications. Adv Drug Deliv Rev 2012; 64: 18-23. http://dx.doi.org/10.1016/j.addr.2012.09.010
Peppas NA, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 2000; 50:27-46. http://dx.doi.org/10.1016/S0939-6411(00)00090-4
Li L, Lee LJ. Photopolymerization of HEMA/DEGDMA hydrogels in solution. Polymer 2005; 46: 11540-11547. http://dx.doi.org/10.1016/j.polymer.2005.10.051
Lin C-C, Metters AT. Hydrogels in controlled release formulations: Network design and mathematical modeling. Adv Drug Deliv Rev 2006; 58: 1379-1408. http://dx.doi.org/10.1016/j.addr.2006.09.004
Chang S-T, Chen L-C, Lin S-B, Chen H-H. Nano-biomaterials application: Morphology and physical properties of bacterial cellulose/gelatin composites via crosslinking Food Hydrocoll 2012; 27: 137-144. http://dx.doi.org/10.1016/j.foodhyd.2011.08.004
Gaspard S, Oujja M, Nalda R, Abrusci C, Catalina F, Bañares L, Castillej M. Submicron foaming in gelatine by nanosecond and femtosecond pulsed laser irradiation Appl Surf Sci 2007; 253: 6420-6424. http://dx.doi.org/10.1016/j.apsusc.2007.01.083
Laymana H, Spigab M-G, Brooksa T, Phamc S, Websterb KA, Andreopoulos FM. The effect of the controlled release of basic fibroblast growth factor from ionic gelatin-based hydrogels on angiogenesis in a murine critical limb ischemic model. Biomaterials 2007; 28: 2646-2654. http://dx.doi.org/10.1016/j.biomaterials.2007.01.044
Chen K-Y, Yao C-H. Repair of bone defects with gelatinbased composites: A review. BioMedicin I 2011; 29-32.
Zhang YZ, Venugopal J, Huang Z-M, Lim CT, Ramakrishna S. Crosslinking of the electrospun gelatin nanofibers. Polymer 2006; 47: 2911-2917. http://dx.doi.org/10.1016/j.polymer.2006.02.046
Olsen D, Yanga C, Bodoa M, Changa R, Leigha S, Baeza J, Carmichaela D, Perälä M, Hämäläinen E-R, Jarvinen M, Polarek J. Recombinant collagen and gelatin for drug delivery. Adv Drug Deliv Rev 2003; 55: 1547- 1567. http://dx.doi.org/10.1016/j.addr.2003.08.008
Haraguchi K & Takehisa T. Nanocomposite hydrogels: A unique organik-ınorganic network structure with Extraordinary mechanical, optical, and swelling/de-swelling propertie. Adv Materials 2002; 14(16): 1120-1124. http://dx.doi.org/10.1002/1521- 4095(20020816)14:16<1120::AID-ADMA1120>3.0.CO;2-9
Teng S, Shi J, Peng B, Chen L. The effect of alginate addition on the structure and morphology of hydroxyapatite/gelatin nanocomposites. Compos Sci Technol 2006; 66: 1532-1538. http://dx.doi.org/10.1016/j.compscitech.2005.11.021
Laymana H, Spigab M-G, Brooks T, Pham, S, Webster KA, Andreopoulos FM. The effect of the controlled release of basic fibroblast growth factor from ionic gelatin-based hydrogels on angiogenesis in a murine critical limb ischemic model. Biomaterials 2007; 28: 2646-2654. http://dx.doi.org/10.1016/j.biomaterials.2007.01.044
Guo T, Zhaob J, Changa J, Dinga Z, Honga H, Chena J, Zhang J. Porous chitosan-gelatin scaffold containing plasmid DNA encoding transforming growth factor-b1 for chondrocytes proliferation. Biomaterials 2006; 27: 1095- 1103. http://dx.doi.org/10.1016/j.biomaterials.2005.08.015
Seki T, Kanbayashi H, Chono S, Tabata Y, Morimoto K, Effects of a sperminated gelatin on the nasal absorption of insulin. Int J Pharm 2007; 338(1-2): 213-8. http://dx.doi.org/10.1016/j.ijpharm.2007.02.004
Zheng JP, Wang CZ, Wang XX, Wang HY, Zhuang H, Yao KD. Preparation of biomimetic three-dimensional gelatin/montmorillonite-chitosan scaVold for tissue engineering. React Funct Polym 2006; 67(9): 780-788. http://dx.doi.org/10.1016/j.reactfunctpolym.2006.12.002
Kommareddy S, Amiji M. Poly(ethylene glycol)-modified thiolated gelatin nanoparticles for glutathione-responsive intracellular DNA delivery. Nanomedicine 2007; 32- 42. http://dx.doi.org/10.1016/j.nano.2006.11.005
Hyoudou K, Nishikawa M, Ikemura M, Kobayashi Y, Mendelsohn A, Miyazaki N, Tabata Y, Yamashita F, Hashida M. Prevention of pulmonary metastasis from subcutaneous tumors by binary system-based sustained delivery of catalase. J Controlled Release 2009; 137: 110-115. http://dx.doi.org/10.1016/j.jconrel.2009.04.005
Aduba DC, Hammer JA, Yuan Q, Yeudall WA, Bowlin GL, Yang H. Semi-interpenetrating network (sIPN) gelatin nanofiber scaffolds for oral mucosal drug delivery. Acta Biomater 2013; 9: 6576-6584. http://dx.doi.org/10.1016/j.actbio.2013.02.006
Fathi A, Lee S, Zhong X, Hon N, Valtchev P, Dehghani F, Fabrication of interpenetrating polymer network to enhance the biological activity of synthetic hydrogels. Polymer 2013; 54(21): 5534-5542. http://dx.doi.org/10.1016/j.polymer.2013.08.052
Ayhan F, Ozkan S. Gentamicin release from photopolymerized PEG Diacrylate and pHEMA hydrogel discs and their in-vitro antimicrobial activities. Drug Deliv 2007; 14(7): 433-439. http://dx.doi.org/10.1080/10717540701202911
Sökmen N, Bican F, Ayhan F, Ayhan H. Chelating Agent Effect on the Release of Gentamicin from PEG-DA Hydrogels, Hacettepe J Biol Chem 2008, 36(4): 347-352.
Modi S, Jain JP Domb AJ, Kumar N. Copolymers of pharmaceutical grade lactic acid and sebacic acid: Drug release behavior and biocompatibility European J Pharm Biopharm 2006; 64: 277-286. http://dx.doi.org/10.1016/j.ejpb.2006.05.013
Rokhade AP, Agnihotri SA, Patil SA, Mallikarjuna NN, Kulkarni PV, Aminabhavi TM. Semi-interpenetrating polymer network microspheres of gelatin and sodium carboxymethyl cellulose for controlled release of ketorolac tromethamine Carbohydr Polym 2006; 65: 243-252. http://dx.doi.org/10.1016/j.carbpol.2006.01.013
Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems Acta Poloniae Pharm Drug Res 67; 3: 217-223, 2010.
Ramakrishna S, Mihira V, Tabitha K. Design and evaluatıon of drug release kinetics of diltiazem hydrochloride sustained release tablets Intern J Medical Pharm Sci 2011; 1(4): 1-13.
Arslan A. Akrilat Bazlı Hidrojellerin Fotopolimerizasyon Yöntemi ile Hazırlanması, Karakterizasyonu ve Kontrollu ????laç Salım Sistemlerinde Kullanımının Ara????tırılması PhD Thesis; co-Adviser: Hacettepe Universitesity, Department of Bioengineering, 2006; A0278572.
Rajan M, Raj V, Al-Arfaj AA. Murugan AM. Hyaluronidase enzyme core-5-fluorouracil-loaded chitosan-PEG-gelatin polymer nanocomposites as targeted and controlled drug delivery vehicles. Int J Pharm 2013; 453: 514-522. http://dx.doi.org/10.1016/j.ijpharm.2013.06.030
