NOVEL SMART pH SENSITIVE CHITOSAN GRAFTED ALGINATE HYDROGEL MICROCAPSULES FOR ORAL PROTEIN DELIVERY: I. PREPARATION AND CHARACTERIZATION
Keywords:
Alginate, Chitosan, Polyelectrolyte complex, Hydrogel, Grafting, ActivationAbstract
Objectives: Preparation and characterization of a new pH sensitive chitosan (CS) grafted alginate (ALG) hydrogel microcapsules for the oral delivery of protein.
Methods: The pH sensitive hydrogel microcapsules were prepared for the first time using grafting to†technique. Firstly, alginate was activated using Ï-Benzoquinone (PBQ) as a coupling agent to graft Chitosan chains later on. Both of activated and grafted alginate microcapsules were characterized by Fourier transform-Infra red spectroscopy (FT-IR), thermal gravimetric analysis (TGA) and the morphological structures were investigated using Scanning electron microscopy (SEM) examination.
Results: It was found that the optimum conditions affecting the activation process and also the swelling degree of the prepared hydrogel microcapsules were 2% ALG, 0.04M PBQ pH10, 45 °C for 2h. In addition, the grafting process depends on the attached amount of PBQ and CS concentration. Maximum grafting efficiency (GE %) and chitosan add-on percentage were 98.6% and 14.8% respectively using 0.3% CS at 40 °C for 3h.
Conclusions: Novel pH sensitive hydrogel microcapsules were prepared via grafting of chitosan molecules on to activated alginate backbone. The formulated microcapsules can be applied as a new pH sensitive carrier for protein drugs.
Â
Downloads
References
Sun J, Tan H. Alginate-based biomaterials for regenerative medicine applications. Materials 2013;6:1285-309.
Lee KY, Mooney DJ. Hydrogels for tissue engineering. Chem Rev 2001;101:1869–79.
Tan H, Marra KG. Injectable biodegradable hydrogels for tissue engineering applications. Materials 2010;3:1746–67.
Kumara A, Srivastava A, Galaev IY, Mattiasson B. Smart polymers: physical forms and bioengineering applications. Prog Polym Sci 2007;32:1205–37.
Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv Drug Delivery Rev 2001;53:321–39.
Gazori T, Khoshayand MR, Azizi E, Yazdizade P, Nomani A, Haririan I. Evaluation of Alginate/chitosan nanoparticles as antisense delivery vector. Formulation, optimization and in vitro characterization. Carbohydrate Polym 2009;77:599–606.
Masteiková R, Chalupová Z, Šklubalová Z. Stimuli-sensitive hydrogels in controlled and sustained drug delivery. Medicina 2003;39:19-24.
Mi F, Tan Y, Liang H, Sung H. In vivo biocompatibility and degradability of a novel injectable-chitosan-based implant. Biomaterials 2002;23:181–91.
Peppas NA, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 2000;50:27–46.
Siegel RA, Falamarzian M, Firestone BA, Moxley BC. pH-controlled release from hydrophobic/polyelectrolyte copolymer hydrogels. J Controlled Release 1988;8:179–82.
Abreu F, Bianchini C, Forte MMC, Kist TBL. Influence of the composition and preparation method on the morphology and swelling behavior of alginate-chitosan hydrogels. Carbohydrate Polym 2008;74:283–9.
Pasparakis G, Bouropoulos N. Swelling studies and in vitro release of verapamil from calcium alginate and calcium alginate–chitosan beads. Int J Pharm 2006;323:34–42.
Ress DA, Welsh EJ. Secondary and tertiary structure of polysaccharides in solutions and gels. Angew Chem Int Ed Engl 1997;16:214–24.
Kim JO, Park JK, Kim JH, Jin SG, Yonga CS, Li DX, et al. Development of polyvinyl alcohol–sodium alginate gelmatrix-based wound dressing system containing nitrofurazone. Int J Pharm 2008;359:79–86.
Li S, Wang X, Zhang X, Yang R, Zhang H, Zhub L, et al. Studies on alginate–chitosan microcapsules and renal arterial embolization in rabbits. J Controlled Release 2002;84:87–98.
Gomez G, Ayala D, Malinconico M, Laurienzo P. Marine derived polysaccharides for biomedical applications: chemical modification approaches. Molecules 2008;13:2069-106.
Pluemsab W, Sakairi N, Furuike T. Synthesis and inclusion property of α-cyclodextrin-linked alginate. Polymer 2005;46:9778–83.
Kulkarni A, Soppimath K, Aminabhavi T, Dave A. Polymeric sodium alginate interpenetrating network beads for the controlled release of chlorpyrifos. J Appl Polym Sci 2002;85:911-8.
Saether HV, Holme HK, Maurstad G, Smidsrød O, Stokke BT. Polyelectrolyte complex formation using alginate and chitosan. Carbohydrate Polym 2008;74:813–21.
Prajapati BG, Sawant KK. Poly electrolyte complex of chitosan alginate for local drug delivery. Int J Chem Tech Res 2009;1:643-8.
George M, Abraham TE. Polyionic hydrocolloids for the intestinal delivery of protein drugs: Alginate and chitosan—a review. J Controlled Release 2006;114:1–14.
Bergera J, Reista M, Mayera JM, Feltb O, Peppas NA, Gurny R. Structure and interactions in covalently and ionicallycrosslinked chitosan hydrogels for biomedical applications. Eur J Pharm Biopharm 2004;57:19–34.
Rinaudo M. Chitin and chitosan: properties and applications. Prog Polym Sci 2006;31:603–32.
Liu TY, Lin YL. Novel pH-sensitive chitosan-based hydrogel for encapsulating poorly water-soluble drugs. Acta Biomaterialia 2010;6:1423-9.
Hsu SH, Whu SW, Hsieh SC, Tsai CL, Chen DC, Tan TS. Evaluation of chitosan-alginate-hyaluronate complexes modified by an RGD-containing protein as tissue-engineering scaffolds for cartilage regeneration. Artif Organs 2004;28:693–703.
Yuan Q, Venkatasubramanian R, Hein S, Misra RDK. A stimulus-responsive magnetic nanoparticle drug carrier: magnetite encapsulated by chitosan-grafted-copolymer. Acta Biomater 2008;4:1024–37.
Liu H, Li H, Cheng WJ, Yang Y, Zhu MY, Zhou CR. Novel injectable calcium phosphate/chitosan composites for bone substitute materials. Acta Biomater 2006;2:557–65.
Gan Q, Wang T, Cochrane C, McCarron P. Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery. Colloids Surf B 2005;44:65-73.
He P, Davis SS, Illum L. In vitro evaluation of the mucoadhesive properties of chitosan microspheres. Int J Pharm 1998;166:75-88.
Li X, Kong X, Shi S, Zheng X, Guo G, Wei Y. Preparation of alginate coated chitosan microparticles for vaccine delivery. BMC Biotechnol 2008;8:89-99.
Wichterle O, Lim D. Hydrophilic gels for biological use. Nature 1960;185:117–8.
Anal AK, Stevens WF. Chitosan–alginate multilayer beads for controlled release of ampicillin. Int J Pharm 2005;290:45–54.
De S, Robinson D. Polymer relationships during preparation of chitosan–alginate and poly-l-lysine–alginate nanospheres. J Controlled Release 2003;89:101–12.
Hari PR, Chandy T, Sharma CP. Chitosan/calcium–alginate beads for oral delivery of insulin. J Appl Polym Sci 1996;59:1795–801.
Sezer AD, Akbuga J. Release characteristics of chitosan treated alginate beads: II. Sustained release of a low molecular drug from chitosan treated alginate beads. J Microencapsul 1999;16:687–96.
Mohy Eldin MS, Seuror E, Nasr M, El-Aassar M, Tieama H. Affinity covalent immobilization of glucoamylase onto Ï-Benzoquinone activated alginate beads: i. beads preparation and characterization. Appl Biochem Biotechnol 2011;164:10–22.
Oliveira AND, Santana HD, Zaia CTBV, Zaia DAM. A study of reaction between quinones and thiourea: determination of thiourea in orange juice. J Food Compos Anal 2004;17:165–77.
Mohy Eldin MS, Omer AM, Soliman EA, Hassan EA. Superabsorbent polyacrylamide grafted carboxymethyl cellulose pH sensitive hydrogel: I. Preparation and characterization. Desalin Water Treat 2013;51:3196–206.
Mohamed F, Bashar A. Graft copolymerization on to Chitosan-1. Grafting of methylmethacrylate using ceric ammonium nitrate as an initiator. Acta Chim Slovaca 2003;50:275-85.
Mohy Eldin MS, El-Sherif HM, Soliman EA, Elzatahry AA, Omer AM. Polyacrylamide-grafted carboxymethyl cellulose: smart pH-Sensitive hydrogel for protein concentration. J Appl Polym Sci 2011;12:469-79.
Xu Y, Zhan C, Fan L, Wang L, Zheng H. Preparation of dual crosslinked alginate-chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system. Int J Pharm 2007;336:329–37.