SYNTHESIS AND CHARACTERIZATION OF THIOLATED JACKFRUIT SEED STARCH AS A COLONIC DRUG DELIVERY CARRIER
Keywords:Starch, Jackfruit seed, Thiolation, Microspheres, Colon targeting
Objective: Site-specific drug delivery into the colonic region is extremely fascinating for local treatment of various colonic diseases like ulcerative colitis, colon cancer but it should be capable of saving the drug from hydrolysis and degradation. The present study reports the application of jackfruit seed starch and its thiol derivative as a drug delivery carrier for the colon.
Methods: The starch was extracted from the jackfruit seeds by water extraction method and modified by the esterification reaction with thioglycolic acid. The thiolated starch was characterized for morphology, functional and flow properties. The safety profile of the thiolated starch was confirmed by acute toxicity study in a mice model as per OECD guidelines 423. The microspheres based on thiolated starch were prepared by ionic gelation method incorporating Ibuprofen as a model drug. The prepared microspheres were characterized for particle size, drug entrapment efficiency, drug loading, compatibility study, surface morphology, in vitro drug release and release kinetics.
Results: The result attributed that starch was successfully modified by the thiolation with a degree of substitution of 3.30. The size of prepared microspheres ranges from 825.5±4.58 to 857±6.24 µm, the entrapment efficiencies ranges from 69.23±1.19 to 76.15±0.83 % and the drug loading capacity ranges from 17.75±0.30 to 46.05±0.49 %. The FT-IR, DSC and XRD studies confirmed that there is no interaction within drug and excipients. The thiolated starch microspheres show the maximum release of drug at pH 7.4 in the presence of rat caecal content as compared to pH 1.2 and pH 6.8 for up to 24 h and are following first order release kinetics.
Conclusion: These results suggest the application of thiolated jackfruit seed starch could be promising as a long-term drug delivery carrier for the colon.
Manek RV, Builders PF, Kolling WM, Emeje M, Kunle OO. Physicochemical and binder properties of starch obtained from Cyperus esculentus. AAPS PharmSciTech 2012;13:379-88.
Henrist D, Bortel LV, Lefebvre R, Remon J. In vitro and in vivo evaluation of starch-based hot stage extruded double matrix systems. J Controlled Release 2001;75:391-400.
Rengsutthi K, Charoenrein S. Physico-chemical properties of jackfruit seed starch (Artocarpus heterophyllus) and its application as a thickener and stabilizer in chilli sauce. LWT-Food Sci Technol 2011;44:1309-13.
Hettiaratchi UPK, Ekanayake S, Welihinda J. Nutritional assessment of a jackfruit (Artocarpus heterophyllus) meal. Ceylon Med J 2011;56:54-8.
Olayinka FS, Olayinka OO, Olu-Owolabi BI, Adebowale KO. Effect of chemical modifications on thermal, rheological and morphological properties of yellow sorghum starch. J Food Sci Technol 2015;52:8364-70.
Chen Q, Haojie Y, Wang L, Abdin ZU, Chen Y, Wang J, et al. Recent progress in chemical modification of starch and its applications. RSC Adv 2015;5:67459-74.
BeMiller JN, Huber KC. Physical modification of food starch functionalities. Annu Rev Food Sci Technol 2015;6:19-69.
Albrecht K, Bernkop Schnürch A. Thiomers: forms, functions and applications to nanomedicine. Nanomedicine 2007;2:41-50.
Bernkop Schnurch A. Thiomers: a new generation of mucoadhesive polymers. J Adv Drug Delivery Rev 2005;57:1569-82.
Bonengel S, Bernkop Schnürch A. Thiomers-from bench to market. J Controlled Release 2014;194:120-9.
Philip AK, Philip B. Colon targeted drug delivery system: a review on primary and novel approaches. Oman Med J 2010;25:70-8.
Vandamme TF, Lenourry A, Charrueau C, Chaumeil JC. The use of polysaccharides to target drugs to the colon. Carbohydr Polym 2002;48:219-31.
Zhang N, Wardwell PR, Bader RA. Polysaccharide-based micelles for drug delivery. Pharmaceutics 2013;5:329-52.
Sinha VR, Kumria R. Polysaccharides in colon-specific drug delivery. Int J Pharm 2001;224:19-38.
Mundargi RC, Patil SA, Agnihotri SA, Aminabhavi TM. Development of polysaccharide-based colon targeted drug delivery systems for the treatment of amoebiasis. J Drug Dev Ind Pharm 2007;33:255-64.
Gyarmati B, Nemethy A, Szilagyi A. Reversible disulphide formation in polymer networks: a versatile functional group from synthesis to applications. Eur Polym J 2013;49:1268-86.
Zhang L, Sang Y, Feng J, Li Z, Zhao A. Polysaccharide-based micro/nanocarriers for oral colon-targeted drug delivery. J Drug Target 2016;24:579-89.
Chen J, Liang Y, Li X, Chen L, Xie F. Supramolecular structure of jackfruit seed starch and its relationship with digestibility and physicochemical properties. Carbohydr Polym 2016;150:269-77.
Singh J, Singh N. Studies on the morphological, thermal and rheological properties of starch separated from some indian potato cultivars. Food Chem 2001;75:67-77.
Gupta B, Anjum S, Ikram S. Preparation of thiolated polyvinyl alcohol hydrogels. J Appl Polym Sci 2013;129:815-21.
Hanif M, Zaman M, Qureshi S. Thiomers: a blessing to evaluating era of pharmaceuticals. Int J Polym Sci 2015;1:1-9.
Kumoro AC, Amalia R, Budiyati CR, Retnowati DS, Ratnawati R. Preparation and characterization of physicochemical properties of glacial acetic acid modified gadung (Diocorea hispida dennst) flours. J Food Sci Technol 2015;52:6615-22.
Bartz J, Goebel JT, Giovanaz MA, Zavareze EDR, Schirmer MA, Dias ARG. Acetylation of barnyardgrass starch with acetic anhydride under iodine catalysis. Food Chem 2015;178:236-42.
Pascoal AM, Di-Medeiros MCB, Batista KA, Leles MIG, Liao LM, Fernandes KF. Extraction and chemical characterization of starch from S. lycocarpum fruits. Carbohydr Polym 2013;98:1304-10.
Puri AV, Puranik VK, Kamble MD, Tauro SJ. Formulation and evaluation of diclofenac sodium tablet using isolated starch from unripe papaya fruits as the disintegrant. Indo Am J Pharm Res 2013;3:9183-9.
Madruga MS, Albuquerque FSM, Silva IRA, Amaral DS, Magnani M, Neto VQ. Chemical, morphological and functional properties of brazilian jackfruit (Artocarpus heterophyllus L.) seeds starch. Food Chem 2014;143:440-5.
Falade KO, Okafor CA. Physical, functional, and pasting properties of flours from corms of two cocoyam (Colocasia esculenta and Xanthosoma sagittifolium) cultivars. J Food Sci Technol 2015;52:3440-8.
Kaur M, Oberoi DPS, Sogi DS, Gill BS. Physicochemical, morphological and pasting properties of acid treated starches from different botanical sources. J Food Sci Technol 2011;48:460-5.
Nadiha MZN, Fazilah A, Bhat R, Karim AA. Comparative susceptibilities of sago, potato and corn starches to alkali treatment. Food Chem 2010;121:1053-9.
Chinma CE, Ariahu CC, Abu JO. Chemical composition, functional and pasting properties of cassava starch and soy protein concentrate blends. J Food Sci Technol 2013;50:1179-85.
Shah RB, Tawakkul MA, Khan MA. Comparative evaluation of flow for pharmaceutical powders and granules. AAPS PharmSciTech 2008;9:250-8.
Remya KS, Beena P, Bijesh PV, Sheeba A. Formulation development, evaluation and comparative study of effects of super disintegrants in cefixime oral disintegrating tablets. J Young Pharm 2010;2:234-9.
Zeng J, Gao H, Li G. Functional properties of wheat starch with different particle size distribution. J Sci Food Agric 2014;94:57-62.
OECD Guideline 423 for Testing of Chemicals. Acute oral toxicity-acute toxic class method; 2001.
Hari BNV, Praneetha T, Prathyusha T, Mounika K, Devi DR. Development of starch-gelatin complex microspheres as sustained release delivery system. J Adv Pharm Technol Res 2012;3:182-7.
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.
Nayak AK, Pal D. Development of pH-sensitive tamarind seed polysaccharide-alginate composite beads for controlled diclofenac sodium delivery using response surface methodology. Int J Biol Macromol 2011;49:784-93.
Patel JK, Patel RP, Amin AF, Patel MM. Formulation and evaluation of mucoadhesive glipizide microspheres. AAPS PharmSciTech 2005;6:49-55.
Thompson CJ, Hansford D, Higgins S, Rostron C, Hutcheon GA, Munday DL. Evaluation of ibuprofen-loaded microspheres prepared from novel copolyesters. Int J Pharm 2007;329:53-61.
Palanisamy M, Khanam J. Cellulose-based matrix microspheres of prednisolone inclusion complex: preparation and characterization. AAPS PharmSciTech 2011;12:388-400.
Gangurde HH, Chavan NV, Mundada AS, Derle DV, Tamizharasi S. Biodegradable chitosan-based ambroxol hydrochloride microspheres: effect of cross-linking agents. J Young Pharm 2011;3:9-14.
Masaelia R, Kashia TSJ, Dinarvand R, Tahriria M, Rakhshand V, Esfandyari-Manesh M. Preparation, characterization and evaluation of drug release properties of simvastatin-loaded PLGA microspheres. Iran J Pharm Res 2016;15:205-11.
Sinko PJ, Singh Y. Martin’s physical pharmacy and pharmaceutical sciences-sixth edition. New York: Lippincott Williams and Wilkins; 2011.
Yandrapu S, Kompella UB. Development of sustained-release microspheres for the delivery of SAR 1118, an LFA-1 antagonist intended for the treatment of vascular complications of the eye. J Ocul Pharmacol Ther 2013;29:236-48.
Nayak AK, Pal D. Blends of jackfruit seed starch-pectin in the development of mucoadhesive beads containing metformin HCl. Int J Biol Macromol 2013;62:137-45.
Ramasamy T, Khandasamy US, Shanmugamb S, Ruttalad H. Formulation and evaluation of chondroitin sulphate tablets of aceclofenac for colon targeted drug delivery. Iran J Pharm Res 2012;11:465-79.
Dash S, Murthy PN, Nath LK, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 2010;67:217-23.
Raymond CR, Paul JS, Marian EQ. Handbook of pharmaceutical excipients. 6th ed. London: Pharmaceutical Press; 2009.
Wasewar K, Patidar S, Agarwal VK. Esterification of lactic acid with ethanol in a pervaporation reactor: modeling and performance study. Desalination 2009;243:305-13.
Schou Pedersen AM, Hansen SH, Moesgaard B, Østergaard J. Kinetics of the esterification of active pharmaceutical ingredients containing carboxylic acid functionality in polyethylene glycol: formulation implications. J Pharm Sci 2014;103:2424-33.
Vollhardt P, Schore N. Organic chemistry structure and function. 6th ed. New York: W. H. Freeman and Company; 2011.
Gilbert HF. Thiol/disulfide exchange equilibria and disulfide bond stability. Methods Enzymol 1995;251:8-28.
Sahnoun M, Ismail N, Kammoun R. Enzymatically hydrolysed, acetylated and dually modified corn starch: physico-chemical, rheological and nutritional properties and effects on cake quality. J Food Sci Technol 2016;53:481-90.
Kumar KJ, Varma AKC, Panpalia SG. Physicochemical and release characteristics of acetylated Indian palmyrah retrograded shoot starch. Int J Biol Macromol 2014;69:108-13.
Osundahunsi OF, Seidu KT, Mueller R. Effect of presence of sulphurdioxide on acetylation and sorption isotherm of acetylated starches from cultivars of cassava. Food Chem 2014;151:168-74.
United State Pharmacopeia USP 29-NF 24. U. S: United States Pharmacopeial Convention; 2008-2010.
Jothy SL, Zakaria Z, Chen Y, Lau YL, Latha LY, Sasidharan S. Acute oral toxicity of methanolic seed extract of Cassia fistula in mice. Molecules 2011;16:5268-82.
Jesus DR, Barbosa LN, Prando TBL, Martins LF, Gasparotto F, Guedes KMR, et al. Ninety-day oral toxicity assessment of an alternative biopolymer for controlled release drug delivery systems obtained from cassava starch acetate. Evid Based Complement Alternat Med 2015;390416:1-7.
Nayak AK, Pal D, Santra K. Development of calcium pectinate-tamarind seed polysaccharide mucoadhesive beads containing metformin HCl. Carbohydr Polym 2014;101:220-30.
Mallappa MK, Kesarla R, Banakar S. Calcium alginate-neusilin US2 nanocomposite microbeads for oral sustained drug delivery of poor water-soluble drug aceclofenac sodium. J Drug Delivery 2015;826981:1-14.
Kim C, Kim M, Oh K. Preparation and evaluation of sustained release microspheres of terbutaline sulfate. Int J Pharm 1994;106:213-9.
Kumbar SG, Kulkarni AR, Aminabhavi M. Crosslinked chitosan microspheres for encapsulation of diclofenac sodium: effect of crosslinking agent. J Microencapsul 2002;19:173-80.
Mundargi RC, Shelke NB, Rokhade AP, Patil SA, Aminabhavi TM. Formulation and in vitro evaluation of novel starch-based tableted microsphere for controlled release of ampicillin. Carbohydr Polym 2008;71:42-53.
Dhawan S, Singla AK, Sinha VR. Evaluation of mucoadhesive properties of chitosan microspheres prepared by different methods. AAPS PharmSciTech 2004;5:1-7.
Zhu X, Su M, Tang S, Wang L, Liang X, Meng F, et al. Synthesis of thiolated chitosan and preparation nanoparticles with sodium alginate for ocular drug delivery. Molecular Vis 2012;18:1973-82.
Khaskheli AR, Sirajuddin, Sherazi STH, Mahesar SA, Kandhro AA, Kalwar NH, et al. Estimation of ibuprofen in urine and tablet formulations by transmission fourier transform infrared spectroscopy by partial least square. Spectrochim Acta A Mol Biomol Spectrosc 2013;102:403-7.
Bulut E. In vitro evaluation of ibuprofen-loaded microspheres prepared from novel chitosan/poly(vinyl alcohol) interpenetrating polymer network. Polym Plast Technol Eng 2014;53:371-8.
Fernandez Carballido A, Herrero Vanrell R, Molina Martinez IT, Pastoriza P. Sterilized ibuprofen-loaded poly(d,l-lactideco-glycolide) microspheres for intra-articular administration: effect of γ-irradiation and storage. J Microencapsul 2004;21:653-65.
Ramteke KH, Jadhav VB, Kulkarni NS, Kharat AR, Diwate SB. Preparation, evaluation and optimization of multiparticulate system of mebendazole for colon targeted drug delivery by using natural polysaccharides. Adv Pharm Bull 2015;5:361-71.
Jain SK, Shukla M, Shrivastava V. Development and in vitro evaluation of ibuprofen mouth dissolving tablets using solid dispersion technique. Chem Pharm Bull 2010;58:1037-42.
Swamy BY, Yun Y. In vitro release of metformin from iron (iii) cross-linked alginate-carboxymethyl cellulose hydrogel beads. Int J Biol Macromol 2015;77:114-9.
Patel N, Lalwani D, Gollmer S, Injeti E, Sari Y, Nesamony J. Development and evaluation of a calcium alginate based oral ceftriaxone sodium formulation. Prog Biomater 2016;5:117-33.
Lim V, Peh KK, Sahudin S. Synthesis, characterisation, and evaluation of a cross-linked disulphide amide-anhydride-containing polymer based on cysteine for colonic drug delivery. Int J Mol Sci 2013;14:24670-91.
Gamcsik MP, Kasibhatla MS, Teeter SD, Colvin OM. Glutathione levels in human tumors. Biomarkers 2012;17:671-91.
Lau YK, Lim V. Colon targeted drug delivery of branch‑chained disulphide cross‑linked polymers: design, synthesis and characterisation studies. Chem Cent J 2016;10:1-19.
Holowka EP, Bhatia SK. Drug delivery: materials design and clinical perspective. New York: Springer; 2014.