Application of PLGA-ion exchange resin microcapsules of sulfasalazine ‎for embolization therapy
DOI:
https://doi.org/10.22317/jcms.v5i5.646Keywords:
Embolization therapy, sulfasalazine, DEAE sephadex A 25 ion exchange resin, PLGA ‎coated microcapsules.‎Abstract
ABSTRACT
Objective: This work involves preparation and evaluation (in vitro/ in vivo) of microcapsules containing sulfasalazine- ion exchange resin complex (resinate) to induce emboli for treatment of solid cancer.
Methods: The drug resin complex (resinate) had been optimized by using drug: resin ratio (1:8), by suspending the resin in sulfasalazine aqueous solution with at 400 rpm for 120 minutes at 50 ºC. For controlling the release of drug, microencapsulation for the resinate was applied where 21 formulas with different resinate: PLGA ratios 2:1, 1:1, 1:2 were prepared by solvent evaporation method to study the effect of different variables including resinate: polymer ratio, stirring speed, effect of temperature and aqueous phase volume on microencapsulation efficiency and percent yield.
Results: The in-vitro release study for the prepared resinate, which had 72% entrapment efficiency, showed 80.992 % of drug released within 15 minutes and the release continued until 99.83% within 75 minutes formula was found to be F19 had 76.70% encapsulation efficiency and 89.40% percent yield. The in vitro release study for selected formula showed that 32% of drug released within 1hour and 78% of drug released within 20 days and the release continued up to 96% within 45 days indicating a controlled release manner with spherical microcapsule of 595µm. The preliminary in vivo work using rabbits showed instant occlusion of the central auricular artery of the rabbit ear leading to ischemia within 3 days that continued to the end of study period
Conclusion: This work show the suitability of microcapsules size to prevent blood flow and forming embolization with controlling release of the drug that may treat the solid tumor.
References
References
‎1.‎ Manisha GS. Oral controlled release drug delivery system- a review. PharmaTutor ‎‎2014;2(8):170-8.‎
‎2.‎ Patel N, Chaudhary A, Soni T, Sambyal M, Jain H,Upadhyay U. Controlled drug ‎delivery system: a review. Indo American J of Pharm Sci 2016;3(3):227-33.‎
‎3.‎ Rahul A S, Sharjeel S, Savitri K, Reginald KA, Yu S Z, Ali K, Rahmi O, ‎Endovascular embolization by transcatheter delivery of particles: past, present, and future. J ‎of Fun Biomat 2017;8(12):1-12.‎
‎4.‎ Ozge IL DB. Ion exchange resins and applications in pharmaceutical technology. ‎Adv J of Pharm Life sci Re 2015;3(2):16-27 ‎
‎5.‎ Siegel H. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug ‎delivery carrier. Polymers (Basel). 2011;3:1377-97.‎
‎6.‎ Chai F, Sun L, He X, Li J, Liu Y, Xiong F, Ge L, Webster TJ, Zheng C. ‎Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with ‎chitosan/alginate by layer by layer technology for antitumor applications. Int J of Nanomed ‎‎2017;12:1791-802.‎
‎7.‎ Azad K A, Piris J, Truelove S C. Optimum dose of sulphasalazine for maintenance ‎treatment in ulcerative colitis. Gut 1980;21:232-40.‎
‎8.‎ Lo M1, Ling V, Low C, Wang YZ, Gout PW. Potential use of the anti-‎inflammatory drug, sulfasalazine, for targeted therapy of pancreatic cancer. Current ‎oncology 2010;17:9-16.‎
‎9.‎ Inderbir S P, Manju N. Ion-exchange resin complexation: Masking the bitter taste of ‎cefuroxime axetil. Rev Cubana de Farm 2011;45(2):171-80 ‎
‎10.‎ R.Mensah-Biney, K.J.Reid, M.T.Hepworth. The loading capacity of selected cation ‎exchange resins and activated carbons for gold-thiourea complex. Minerals Engineering. ‎‎1995;8(1):125-46.‎
‎11.‎ Anand V, Kandarapu R, Garg S. Ion-exchange resins: carrying drug delivery ‎forward. Drug del Today 2011;6:905-914.‎
‎12. Deepak K. Development of taste masked levofloxacin oral suspension using ion ‎exchange resinates. J of Chem and Pharm Res 2016;8(7):385-94.‎
‎13.‎ Obeidat WM, Price JC.. Evaluation of enteric matrix microspheres prepared by ‎emulsion–solvent evaporation using scanning electron microscopy. J of Microencapsulation ‎‎2004;21:47 – 57.‎
‎14.‎ A.V Yadav, A. S. Shete, A.P. Dabke, V.R. Shinde. Formulation and in-vitro ‎evaluation of aceclofenac microcapsules. Int J PharmTech Research 2009;1(2):135-8.‎
‎15.‎ Jyothi N, Muthu P, Narayan S, Surya P, Seetha R. Microencapsulation techniques, ‎factors influencing encapsulation efficiency. J of Microencapsulation. 2010;27:187-97.‎
‎16.‎ Jafari S. Mahdi, Assadpoor E, He Y. Encapsulation efficiency of food flavours and ‎oils during spray drying. Drying Tech 2008;26(7):816-35.‎
‎17.‎ Dhakar C, Maurya S, Ps Sagar B, Bhagat S, Prajapati S. Variables influencing the ‎drug entrapment efficiency of microspheres: a pharmaceutical review. Der Pharmacia Lettre ‎‎2010;2(5):102-16.‎
‎18.‎ Yan J, Wang F, Chen J, Liu T. Preparation and characterization of irinotecan loaded ‎cross-linked bovine serum albumin beads for liver cancer chemoembolization therapy. Int J ‎of Polymer Sci 2016;1:1-8.‎
‎19.‎ Paul K. Appraisal of the laser diffraction particle-sizing. Pharm Tech 2005;29:88-96.‎
‎20.‎ Prakash K, Pradeep R. Preparation and characterization of lamivudine microcapsules ‎using various cellulose polymers. Tropical J of Pharm Res 2007;6(4):841-847.‎
‎21.‎ Lee SY, Choi JW, Lee JY, Kim DD, Kim HC, Cho HJ. Hyaluronic ‎acid/doxorubicin nanoassembly-releasing microspheres for the transarterial ‎chemoembolization of a liver tumor. Drug Deliv 2018;25(1):1472-1483 .‎
‎22.‎ Sharma K, Bascal Z, Kilpatrick H, Ashrafi K, Willis S, Dreher M. Long-term ‎biocompatibility, imaging appearance and tissue effects associated with delivery of a novel ‎radiopaque embolization bead for image-guided therapy. Biomaterials 2016;103:293-304.‎
‎23.‎ Zhou X, Kong M, Cheng XJ, Jing L. In vitro and in vivo evaluation of chitosan ‎microspheres with different deacetylation degree as potential embolic agent. Carbohydrate ‎Polymers 2014;113:304-13.‎
‎24.‎ Wikströms. Sephadex® ion exchange media. Edition AA Data file ion exchange ‎chromatography 2007:1-8‎
‎25.‎ Irwin W, Alphar H O. Drug delivery By ion exchange resin Part III- interaction ‎of ester prodrugs of propranolol with cation exchange resin. Drug Dev Ind Pharm ‎‎1987;13(9):2047 – 66.‎
‎26.‎ M. V. Srikanth, N. S. Rao, M. U. Uhumwangho, and K. V. Ramana Murthy. Ion-‎exchange resins as controlled drug delivery carriers. J of Sci Res 2010;2(3):597-611.‎
‎27.‎ Jyothi N, Muthu Prasanna P, Narayan Sakarkar S, Surya Prabha K, Seetha Ramaiah ‎P, Srawan GY. Microencapsulation techniques, factors influencing encapsulation efficiency. ‎J Microencapsul. 2010;27(3):187-197. ‎
‎28.‎ Banerjee. Interpenetrating polymer network (IPN) hydrogel microspheres for oral ‎controlled release application. Int J of Bio and Macromol 2012; 50:198-206.‎
‎29.‎ Othman M. Ariff A, R. Kapri M, R. Solis L. Growth enhancement of probiotic ‎pediococcus acidilactici by extractive fermentation of lactic acid exploiting anion-exchange ‎resin. Front Microbiol. 2018;9:2554.‎
‎30.‎ Dhakar RC, Maurya S, Ps Sagar B, Bhagat S, Prajapati SK, Prakash Jain C. ‎Variables Influencing the Drug Entrapment Efficiency of Microspheres: A Pharmaceutical ‎Review. Der Pharmacia Lettre 2010, 2(5): 102-116. ‎
‎31.‎ Jyothi N, Prasanna PM, Sakarkar SN, Prabha KS, Ramaiah PS, Srawan GY. ‎Microencapsulation techniques, factors influencing encapsulation efficiency. J of ‎Microencapsulation 2010;27(3):187-197.‎
‎32.‎ Alexandridou S, Kiparissides C. Production of oil-containing polyterephthalamide ‎microcapsules by interfacial polymerization. An experimental investigation of the effect of ‎process variables on the microcapsule size distribution. J of Microencapsulation ‎‎1994;11(6):603-614.‎
‎33.‎ Bala V M, Tegk M. Studies on influence of process variables on performance of ‎gliclazide mucoadhesive microcapsules. Asian J of Pharm and Clin Res 2011;5:167-74.‎
‎34.‎ Chella N, Yada KK, Vempati R. Preparation and evaluation of ethyl cellulose ‎microspheres containing diclofenac Sodium by novel W/O/O emulsion method . J of Pharm ‎Sci Res 2010;2(12):884-888.‎
‎35.‎ Jelvehgari M, Hassanzadeh D, Kiafar F, Delf Loveym B, S A. Preparation and ‎determination of drug-polymer interaction and in-vitro release of mefenamic acid ‎microspheres made of cellulose acetate phthalate and/or ethylcellulose polymers. Iranian j of ‎Pharm Res 2011;10(3):457- 467.‎
‎36.‎ Jelvehgari M, Nokhodchi A, Rezapour M, Valizadeh H. Effect of formulation and ‎processing variables on the characteristics of tolmetin microspheres prepared by double ‎emulsion solvent diffusion method. Indian J of Pharm Sci 2010;72(1):72-78.‎
‎37.‎ Choi HK PR, Nepal PR and Chun MK, . Preparation of floating microspheres for ‎fish farming. Int J of Pharm Sci 2007;341: 85-90.‎
‎38.‎ Swaine T, Tang Y, Garcia P, John J, Waters LJ, Lewis AL. Evaluation of ion ‎exchange processes in drug-eluting embolization beads by use of an improved flow-through ‎elution method. European J of Pharm Sci 2016;93:351-359.‎
‎39.‎ Aman RM, Meshali MM, Abdelghani GM. Ion-exchange complex of famotidine: ‎sustained release and taste masking approach of stable liquid dosage form. Drug Disc & ‎Thera 2014;8(6):268-275.‎
‎40.‎ Samprasit W, Akkaramongkolporn P, Ngawhirunpat T, Rojanarata T. Meloxicam ‎taste-masked oral disintegrating tablet with dissolution enhanced by ion exchange resins ‎and cyclodextrin. Pharm Science Technology. 2013;14(3):1118-28.‎
‎41.‎ Reham M. Aman MMM, Galal M. Abdelghani. Ion-exchange complex of ‎famotidine: sustained release and taste masking approach of stable liquid dosage form. ‎Drug Disc & Thera 2014;8(6):268-275.‎
‎42.‎ Akbarzadeh A, Mikaeili H, Zarghami N, Mohammad R, Barkhordari A. Preparation ‎and in vitro evaluation of doxorubicin-loaded Fe₃O₄ magnetic nanoparticles modified ‎with biocompatible copolymers. Int J of Nanomed 2012;7:511-26.‎
‎43. Kapoor D, Bhatia A, Kaur R, Sharma R, Kaur G, Dhawan S. PLGA: A unique ‎polymer for drug delivery. Ther Deliv 2015;6(1):41-58.‎
‎44.‎ Choi JW, Park JH, Cho HR, Chung JW, Kim DD, Kim HC, Cho HJ. Sorafenib and ‎‎2,3,5-triiodobenzoic acid-loaded imageable microspheres for transarterial embolization of a ‎liver tumor. Sci Rep 2017;7(1):554.‎
‎45.‎ Ketie Saralidze, Leo H. Koole, Menno L.W. Knetsch. Polymeric microspheres for ‎medical applications. Materials (Basel) 2010; 3(6): 3537–3564.‎
‎1.‎ Manisha GS. Oral controlled release drug delivery system- a review. PharmaTutor ‎‎2014;2(8):170-8.‎
‎2.‎ Patel N, Chaudhary A, Soni T, Sambyal M, Jain H,Upadhyay U. Controlled drug ‎delivery system: a review. Indo American J of Pharm Sci 2016;3(3):227-33.‎
‎3.‎ Rahul A S, Sharjeel S, Savitri K, Reginald KA, Yu S Z, Ali K, Rahmi O, ‎Endovascular embolization by transcatheter delivery of particles: past, present, and future. J ‎of Fun Biomat 2017;8(12):1-12.‎
‎4.‎ Ozge IL DB. Ion exchange resins and applications in pharmaceutical technology. ‎Adv J of Pharm Life sci Re 2015;3(2):16-27 ‎
‎5.‎ Siegel H. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug ‎delivery carrier. Polymers (Basel). 2011;3:1377-97.‎
‎6.‎ Chai F, Sun L, He X, Li J, Liu Y, Xiong F, Ge L, Webster TJ, Zheng C. ‎Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with ‎chitosan/alginate by layer by layer technology for antitumor applications. Int J of Nanomed ‎‎2017;12:1791-802.‎
‎7.‎ Azad K A, Piris J, Truelove S C. Optimum dose of sulphasalazine for maintenance ‎treatment in ulcerative colitis. Gut 1980;21:232-40.‎
‎8.‎ Lo M1, Ling V, Low C, Wang YZ, Gout PW. Potential use of the anti-‎inflammatory drug, sulfasalazine, for targeted therapy of pancreatic cancer. Current ‎oncology 2010;17:9-16.‎
‎9.‎ Inderbir S P, Manju N. Ion-exchange resin complexation: Masking the bitter taste of ‎cefuroxime axetil. Rev Cubana de Farm 2011;45(2):171-80 ‎
‎10.‎ R.Mensah-Biney, K.J.Reid, M.T.Hepworth. The loading capacity of selected cation ‎exchange resins and activated carbons for gold-thiourea complex. Minerals Engineering. ‎‎1995;8(1):125-46.‎
‎11.‎ Anand V, Kandarapu R, Garg S. Ion-exchange resins: carrying drug delivery ‎forward. Drug del Today 2011;6:905-914.‎
‎12. Deepak K. Development of taste masked levofloxacin oral suspension using ion ‎exchange resinates. J of Chem and Pharm Res 2016;8(7):385-94.‎
‎13.‎ Obeidat WM, Price JC.. Evaluation of enteric matrix microspheres prepared by ‎emulsion–solvent evaporation using scanning electron microscopy. J of Microencapsulation ‎‎2004;21:47 – 57.‎
‎14.‎ A.V Yadav, A. S. Shete, A.P. Dabke, V.R. Shinde. Formulation and in-vitro ‎evaluation of aceclofenac microcapsules. Int J PharmTech Research 2009;1(2):135-8.‎
‎15.‎ Jyothi N, Muthu P, Narayan S, Surya P, Seetha R. Microencapsulation techniques, ‎factors influencing encapsulation efficiency. J of Microencapsulation. 2010;27:187-97.‎
‎16.‎ Jafari S. Mahdi, Assadpoor E, He Y. Encapsulation efficiency of food flavours and ‎oils during spray drying. Drying Tech 2008;26(7):816-35.‎
‎17.‎ Dhakar C, Maurya S, Ps Sagar B, Bhagat S, Prajapati S. Variables influencing the ‎drug entrapment efficiency of microspheres: a pharmaceutical review. Der Pharmacia Lettre ‎‎2010;2(5):102-16.‎
‎18.‎ Yan J, Wang F, Chen J, Liu T. Preparation and characterization of irinotecan loaded ‎cross-linked bovine serum albumin beads for liver cancer chemoembolization therapy. Int J ‎of Polymer Sci 2016;1:1-8.‎
‎19.‎ Paul K. Appraisal of the laser diffraction particle-sizing. Pharm Tech 2005;29:88-96.‎
‎20.‎ Prakash K, Pradeep R. Preparation and characterization of lamivudine microcapsules ‎using various cellulose polymers. Tropical J of Pharm Res 2007;6(4):841-847.‎
‎21.‎ Lee SY, Choi JW, Lee JY, Kim DD, Kim HC, Cho HJ. Hyaluronic ‎acid/doxorubicin nanoassembly-releasing microspheres for the transarterial ‎chemoembolization of a liver tumor. Drug Deliv 2018;25(1):1472-1483 .‎
‎22.‎ Sharma K, Bascal Z, Kilpatrick H, Ashrafi K, Willis S, Dreher M. Long-term ‎biocompatibility, imaging appearance and tissue effects associated with delivery of a novel ‎radiopaque embolization bead for image-guided therapy. Biomaterials 2016;103:293-304.‎
‎23.‎ Zhou X, Kong M, Cheng XJ, Jing L. In vitro and in vivo evaluation of chitosan ‎microspheres with different deacetylation degree as potential embolic agent. Carbohydrate ‎Polymers 2014;113:304-13.‎
‎24.‎ Wikströms. Sephadex® ion exchange media. Edition AA Data file ion exchange ‎chromatography 2007:1-8‎
‎25.‎ Irwin W, Alphar H O. Drug delivery By ion exchange resin Part III- interaction ‎of ester prodrugs of propranolol with cation exchange resin. Drug Dev Ind Pharm ‎‎1987;13(9):2047 – 66.‎
‎26.‎ M. V. Srikanth, N. S. Rao, M. U. Uhumwangho, and K. V. Ramana Murthy. Ion-‎exchange resins as controlled drug delivery carriers. J of Sci Res 2010;2(3):597-611.‎
‎27.‎ Jyothi N, Muthu Prasanna P, Narayan Sakarkar S, Surya Prabha K, Seetha Ramaiah ‎P, Srawan GY. Microencapsulation techniques, factors influencing encapsulation efficiency. ‎J Microencapsul. 2010;27(3):187-197. ‎
‎28.‎ Banerjee. Interpenetrating polymer network (IPN) hydrogel microspheres for oral ‎controlled release application. Int J of Bio and Macromol 2012; 50:198-206.‎
‎29.‎ Othman M. Ariff A, R. Kapri M, R. Solis L. Growth enhancement of probiotic ‎pediococcus acidilactici by extractive fermentation of lactic acid exploiting anion-exchange ‎resin. Front Microbiol. 2018;9:2554.‎
‎30.‎ Dhakar RC, Maurya S, Ps Sagar B, Bhagat S, Prajapati SK, Prakash Jain C. ‎Variables Influencing the Drug Entrapment Efficiency of Microspheres: A Pharmaceutical ‎Review. Der Pharmacia Lettre 2010, 2(5): 102-116. ‎
‎31.‎ Jyothi N, Prasanna PM, Sakarkar SN, Prabha KS, Ramaiah PS, Srawan GY. ‎Microencapsulation techniques, factors influencing encapsulation efficiency. J of ‎Microencapsulation 2010;27(3):187-197.‎
‎32.‎ Alexandridou S, Kiparissides C. Production of oil-containing polyterephthalamide ‎microcapsules by interfacial polymerization. An experimental investigation of the effect of ‎process variables on the microcapsule size distribution. J of Microencapsulation ‎‎1994;11(6):603-614.‎
‎33.‎ Bala V M, Tegk M. Studies on influence of process variables on performance of ‎gliclazide mucoadhesive microcapsules. Asian J of Pharm and Clin Res 2011;5:167-74.‎
‎34.‎ Chella N, Yada KK, Vempati R. Preparation and evaluation of ethyl cellulose ‎microspheres containing diclofenac Sodium by novel W/O/O emulsion method . J of Pharm ‎Sci Res 2010;2(12):884-888.‎
‎35.‎ Jelvehgari M, Hassanzadeh D, Kiafar F, Delf Loveym B, S A. Preparation and ‎determination of drug-polymer interaction and in-vitro release of mefenamic acid ‎microspheres made of cellulose acetate phthalate and/or ethylcellulose polymers. Iranian j of ‎Pharm Res 2011;10(3):457- 467.‎
‎36.‎ Jelvehgari M, Nokhodchi A, Rezapour M, Valizadeh H. Effect of formulation and ‎processing variables on the characteristics of tolmetin microspheres prepared by double ‎emulsion solvent diffusion method. Indian J of Pharm Sci 2010;72(1):72-78.‎
‎37.‎ Choi HK PR, Nepal PR and Chun MK, . Preparation of floating microspheres for ‎fish farming. Int J of Pharm Sci 2007;341: 85-90.‎
‎38.‎ Swaine T, Tang Y, Garcia P, John J, Waters LJ, Lewis AL. Evaluation of ion ‎exchange processes in drug-eluting embolization beads by use of an improved flow-through ‎elution method. European J of Pharm Sci 2016;93:351-359.‎
‎39.‎ Aman RM, Meshali MM, Abdelghani GM. Ion-exchange complex of famotidine: ‎sustained release and taste masking approach of stable liquid dosage form. Drug Disc & ‎Thera 2014;8(6):268-275.‎
‎40.‎ Samprasit W, Akkaramongkolporn P, Ngawhirunpat T, Rojanarata T. Meloxicam ‎taste-masked oral disintegrating tablet with dissolution enhanced by ion exchange resins ‎and cyclodextrin. Pharm Science Technology. 2013;14(3):1118-28.‎
‎41.‎ Reham M. Aman MMM, Galal M. Abdelghani. Ion-exchange complex of ‎famotidine: sustained release and taste masking approach of stable liquid dosage form. ‎Drug Disc & Thera 2014;8(6):268-275.‎
‎42.‎ Akbarzadeh A, Mikaeili H, Zarghami N, Mohammad R, Barkhordari A. Preparation ‎and in vitro evaluation of doxorubicin-loaded Fe₃O₄ magnetic nanoparticles modified ‎with biocompatible copolymers. Int J of Nanomed 2012;7:511-26.‎
‎43. Kapoor D, Bhatia A, Kaur R, Sharma R, Kaur G, Dhawan S. PLGA: A unique ‎polymer for drug delivery. Ther Deliv 2015;6(1):41-58.‎
‎44.‎ Choi JW, Park JH, Cho HR, Chung JW, Kim DD, Kim HC, Cho HJ. Sorafenib and ‎‎2,3,5-triiodobenzoic acid-loaded imageable microspheres for transarterial embolization of a ‎liver tumor. Sci Rep 2017;7(1):554.‎
‎45.‎ Ketie Saralidze, Leo H. Koole, Menno L.W. Knetsch. Polymeric microspheres for ‎medical applications. Materials (Basel) 2010; 3(6): 3537–3564.‎
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Published
2019-10-26
How to Cite
Wohaib, A. Z., Maraie, N. K., & Jassim, G. A. (2019). Application of PLGA-ion exchange resin microcapsules of sulfasalazine ‎for embolization therapy. Journal of Contemporary Medical Sciences, 5(5), 264–273. https://doi.org/10.22317/jcms.v5i5.646
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