DEVELOPMENT, CHARACTERIZATION AND IN VITRO RELEASE KINETIC STUDIES OF IBANDRONATE LOADED CHITOSAN NANOPARTICLES FOR EFFECTIVE MANAGEMENT OF OSTEOPOROSIS

S. PATHAK; S. P. VYAS; A. PANDEY

doi:10.22159/ijap.2021v13i6.42697

Authors

S. PATHAK Department of Chemistry, Dr. H. S. Gour Central University, Sagar (M.P.), India 470003
S. P. VYAS Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar (M. P.), India 470003
A. PANDEY Department of Chemistry, Dr. H. S. Gour Central University, Sagar (M.P.), India 470003

DOI:

https://doi.org/10.22159/ijap.2021v13i6.42697

Keywords:

Bisphosphonate, Bone mineral density (BMD), Ion gelation, Nanoparticle, Osteoporosis, Release kinetics

Abstract

Objective: The objective of the present study was to develop, optimize, and evaluate Ibandronate-sodium loaded chitosan nanoparticles (Ib-CS NPs) to treat osteoporosis.

Methods: NPs were prepared by the Ionic gelation method and optimized for various parameters such as the effect of concentration of chitosan, sodium tripolyphosphate (TPP), and pH effect on particle size polydispersity index (PDI), zeta potential, and entrapment efficiency. The prepared nanoparticles were characterized using particle size analyzer (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and Fourier-Transform Infrared spectroscopy (FTIR).

Results: Formulated NPs were obtained in the average nano size in the range below 200 nm in TEM, SEM, and DLS studies. The particle size and encapsulation efficiency of the optimized formulation were 176.1 nm and 63.28%, respectively. The release profile of NPs was depended on the dissolution medium and followed the First-order release kinetics.

Conclusion: Bisphosphonates are the most commonly prescribed drugs for treating osteoporosis in the US and many other countries, including India. Ibandronate is a widely used anti-osteoporosis drug, exhibits a strong inhibitory effect on bone resorption performed by osteoclast cells. Our results indicated that Ibandronate sodium-loaded chitosan nanoparticles provide an effective medication for the treatment of osteoporosis.

Downloads

Download data is not yet available.

References

Kawalkar AK. A comprehensive review on osteoporosis. J Trauma Orthopaedics. 2014;9:3-12.

Rapp K, Rothenbacher D, Magaziner J, Becker C, Benzinger P, König HH, Jaensch A, Büchele G. Risk of nursing home admission after femoral fracture compared with stroke, myocardial infarction, and pneumonia. J Am Med Dir Assoc. 2015;16(8):715.e7-715.e12. doi: 10.1016/j.jamda.2015.05.013, PMID 26142060.

Dhaliwal R, Mikhail M, Usera G, Stolberg A, Islam S, Ragolia L, Aloia JF. The relationship of physical performance and osteoporosis prevention with vitamin D in older African Americans (PODA). Contemp Clin Trials. 2018;65:39-45. doi: 10.1016/j.cct.2017.11.015, PMID 29221945.

Weaver CM, Alexander DD, Boushey CJ. Calcium plus vitamin D supplementation and risk of fractures. Osteoporos Int. 2016;2:367-76.

Thiede S, Wosniok PR, Herkommer D, Debnar T, Tian M, Wang T, Schrempp M, Menche D. Cover picture: total synthesis of leupyrrins A 1 and B 1, Highly potent antifungal agents from the myxobacterium sorangium cellulosum. Chem Eur J. 2017;23(14):3222. doi: 10.1002/chem.201605970.

Akgun B, Avci D. Synthesis and evaluations of bisphosphonate-containing monomers for dental materials. J Polym Sci A Polym Chem. 2012;50(23):4854-63. doi: 10.1002/pola.26305.

Reginster JY. Oral and intravenous ibandronate in the management of postmenopausal osteoporosis: A comprehensive review. Curr Pharm Des. 2005;11(28):3711-28. doi: 10.2174/138161205774580750, PMID 16305506.

Shukla J. CaCO3 microparticle containing ibandronate-Alginate beads for improved adherence to oral bisphosphonate therapy: formulation and in vitro release. Int J Pharm. 2013;3:340-7.

Gu W, Wu C, Chen J, Xiao Y. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration. Int J Nanomedicine. 2013;8:2305-17. doi: 10.2147/IJN.S44393, PMID 23836972.

Roy SG, Shirsat NS, Mishra AC, Waghulde SO, Kale MK. A review on chitosan nanoparticles applications in drug delivery. J Pharmacogn Phytochem. 2018;7(SP6):01-4. doi: 10.22271/phyto.2018.v7.isp6.1.01.

Sacco P, Brun F, Donati I, Porrelli D, Paoletti S, Turco G. On the correlation between the microscopic structure and properties of phosphate-cross-linked chitosan gels. ACS Appl Mater Interfaces. 2018;10(13):10761-70. doi: 10.1021/acsami.8b01834, PMID 29569895.

Iswanti FC, Nurulita I, Djauzi S, Sadikin M, Witarto AB, Yamazaki T. Preparation, characterization, and evaluation of chitosan-based nanoparticles as CpG ODN carriers. Biotechnol Biotechnol Equip. 2019;33(1):390-6. doi: 10.1080/ 13102818.2019.1578690.

Pimple S. Formulation development and compatibility study of ibandronate sodium injection (3 mg/3 ml). J Chem Pharm Res. 2014;6:400-7.

Mithal A, Bansal B, Kyer CS, Ebeling P. The Asia-pacific regional audit-epidemiology, costs, and burden of osteoporosis in India 2013: a report of international osteoporosis foundation. Indian J Endocrinol Metab. 2014;18(4):449-54. doi: 10.4103/2230-8210.137485, PMID 25143898.

Leslie WD. Clinical review: ethnic differences in bone mass--clinical implications. J Clin Endocrinol Metab. 2012;97(12):4329-40. doi: 10.1210/jc.2012-2863, PMID 23055542.

Khadilkar AV, Mandlik RM. Epidemiology and treatment of osteoporosis in women: an Indian perspective. Int J Womens Health. 2015;7:841-50. doi: 10.2147/IJWH.S54623, PMID 26527900.

Divya K, Vijayan S, George TK, Jisha MS. Antimicrobial properties of chitosan nanoparticles: mode of action and factors affecting activity. Fibers Polym. 2017;18(2):221-30. doi: 10.1007/s12221-017-6690-1.

Huang YC, Li RY. Preparation and characterization of antioxidant nanoparticles composed of chitosan and fucoidan for antibiotics delivery. Mar Drugs. 2014;12(8):4379-98. doi: 10.3390/md12084379, PMID 25089950.

Olivera S, Muralidhara HB, Venkatesh K, Guna VK, Gopalakrishna K, Kumar K Y. Potential applications of cellulose and chitosan nanoparticles/composites in wastewater treatment: a review. Carbohydr Polym. 2016;153:600-18. doi: 10.1016/j.carbpol.2016.08.017, PMID 27561533.

Bohrey S, Chourasiya V, Pandey A. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in vitro drug release and release kinetic study. Nano Converg. 2016;3(1):3. doi: 10.1186/s40580-016-0061-2, PMID 28191413.

Chourasiya V, Bohrey S, Pandey A. Polymeric nanoparticles containing ramipril Using biodegradable polymer: preparation, Optimisation by 23 factorial design, Characterisation and in vitro drug release kinetics. Oxid Commun. 2017;40:1355-66.

Cosman F, De Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R, National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359-81. doi: 10.1007/s00198-014-2794-2, PMID 25182228.

Inta O, Yoksan R, Limtrakul J. Hydrophobically modified chitosan: A bio-based material for an active antimicrobial film. Mater Sci Eng C Mater Biol Appl. 2014;42:569-77. doi: 10.1016/j.msec.2014.05.076, PMID 25063155.

Jeon SJ, Oh M, Yeo WS, Galvao KN, Jeong KC. Underlying mechanism of antimicrobial activity of chitosan microparticles and implications for the treatment of infectious diseases. PLOS ONE. 2014;9(3):e92723. doi: 10.1371/journal.pone.0092723, PMID 24658463.

Rampino A, Borgogna M, Blasi P, Bellich B, Cesàro A. Chitosan nanoparticles: preparation, size evolution and stability. Int J Pharm. 2013;455(1-2):219-28. doi: 10.1016/j.ijpharm.2013. 07.034, PMID 23886649.

Grillo R, Pereira AE, Nishisaka CS, de Lima R, Oehlke K, Greiner R, Fraceto LF. Chitosan/tripolyphosphate nanoparticles loaded with paraquat herbicide: an environmentally safer alternative for weed control. J Hazard Mater. 2014;278:163-71. doi: 10.1016/j.jhazmat.2014.05.079, PMID 24968252.

Gautam L, Sharma R, Shrivastava P, Vyas S, Vyas SP. Development and characterization of biocompatible mannose functionalized mesospheres: an effective chemotherapeutic approach for lung cancer targeting. AAPS PharmSciTech. 2020;21(5):190. doi: 10.1208/s12249-020-01742-9, PMID 32661573.

Ramteke KH. Mathematical models of drug dissolution: a review. Sch Acad J Pharmacol. 2014;3:388-96.

Rasad MK, Alhamza HK, Jamal AA. Development of sustained release alogliptin tablets using a multiparticulates system made of bentonite. Int J Appl Pharm. 2021;13:68-73.

Tripathi SK, Patel B, Shukla S, Pachouri C, Pathak S, Pandey A. Donepezil loaded PLGA Nanoparticles, from Modified Nano-Precipitation, an Advanced Drug Delivery System to treat Alzheimer disease. J Phys: Conf Ser. 2021;2020(1849):012001. doi: 10.1088/1742-6596/1849/1/012001.

Calvo P, Remunan Lopez C, Vila Jato JL, Alonso MJ. Chitosan and chitosan/ethylene oxide-propylene oxide block copolymer nanoparticles as novel carriers for proteins and vaccines. Pharm Res. 1997;14(10):1431-6. doi: 10.1023/ a:1012128907225, PMID 9358557.

Iswandana R, Putri KSS, Dwiputra R, Yanuari T, Sari SP, Djajadisastra J. Raditya iswandana, kurnia sari setio putri, randika dwiputra, tryas yanuari, santi purna sari, joshita djajadisastra. Int J App Pharm. 2017;9(5):109-15. doi: 10.22159/ijap.2017v9i5.20842.

Severino PC, da Silva CF, da Silva MA, Santana MHA, Souto EB. Chitosan Ccross-llinked ppentasodium ttripolyphosphate mmicro/nnanoparticles pproduced by iionotropic ggelation. Sugar Tech. 20142016;18(1):49-54. doi: 10.1007/s12355-014-0360-z.

Sailaja AK, Amreshwar P, Chakravarty P. Different techniques used for the preparation of nanoparticles using natural polymers and their application. Int J Pharm Sci. 2011;3:45-50.

Othman N, Masarudin MJ, Kuen CY, Dasuan NA, Abdullah LC, Md Jamil SNA. Synthesis and ooptimization of cchitosan nnanoparticles lloaded with l-aascorbic aacid and tthymoquinone. Nanomaterials (Basel). 2018;8(11):920. doi: 10.3390/nano8110920, PMID 30405074.

Saini D, Fazil M, Ali MM, Baboota S, Ali J. Formulation, development and optimization of raloxifene-loaded chitosan nanoparticles for treatment of osteoporosis. Drug Delivery (Informa Healthcare USA). 2015;22(6):823-36. doi: 10.3109/10717544.2014.900153, PMID 24725026.

Weng J, Tong HHY, Chow SF. In vitro rrelease sstudy of the ppolymeric ddrug nnanoparticles: ddevelopment and vvalidation of a nnovel mmethod. Pharmaceutics. 2020;12(8):732. doi: 10.3390/pharmaceutics12080732, PMID 32759786.

Y Zambito Y, Pedreschi E, Di Colo G. Is dialysis a reliable method for studying drug release from nanoparticulate systems?-A case study. Int J Pharm. 2012;434(1-2):28-34. doi: 10.1016/j.ijpharm.2012.05.020, PMID 22617795.

Reddy GM, Bhaskar BV, Reddy PP, Ashok S, Sudhakar P, Babu JM, Vyas K, Mukkanti K. Structural identification and characterization of potential impurities of pantoprazole sodium. J Pharm Biomed Anal. 2007;45(2):201-10. doi: 10.1016/j.jpba.2007.05.032, PMID 17629653.

Hanif M, Shah S, Rasul A, Abbas G, Zaman M, Amjad MW, Abdul Ghafoor Raja M, Khan HU, Ashfaq M, Iqbal O. Enhancement of oral bioavailability of ibandronate through gastroretentive raft

forming drug delivery system: in vitro and in vivo evaluation. Int J Nanomed. 2020;15:4847-58. doi: 10.2147/IJN.S255278, PMID 32764922.

Karavas E, Georgarakis M, Docoslis A, Bikiaris D. Combining SEM, TEM, and micro-Raman techniques to differentiate between the amorphous molecular level dispersions and nanodispersions of a poorly water-soluble drug within a polymer matrix. Int J Pharm. 2007;340(1-2):76-83. doi: 10.1016/j.ijpharm.2007.03.037, PMID 17478064.

Cont RD. A physiologically oriented mathematical model for the description of in vivo drug release and absorption. ADMET and DMPK. 2014;2:80-97.

Dubey S, Vyas SP. Emulsomes for lipophilic anticancer drug delivery: development, optimization and in vitro drug release kinetic study. Int J Appl Pharm. 2021;13:114-21.

Singhvi G, Sing M. Review: in vitro drug release characterization models. IJPSR. 2011;1:77-84.