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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Research Article

Hyaluronic Acid Modified Risedronate and Teriparatide Co-loaded Nanocarriers for Improved Osteogenic Differentiation of Osteoblasts for the Treatment of Osteoporosis

Author(s): Mohammed A.S. Abourehab*

Volume 25, Issue 27, 2019

Page: [2975 - 2988] Pages: 14

DOI: 10.2174/1381612825666190801140703

Price: $65


Background: Owing to its multifactorial intricate pathogenesis, combined therapeutic regimen is considered appropriate for the treatment of osteoporosis. However, a multi-drug regimen is also associated with adverse effects due to the non-specific distribution of drugs. Therefore, the present study aims for efficient codelivery of risedronate (RDN) (a potent bone anti-resorptive drug) and teriparatide (TPD) (anabolic agent) as hyaluronic acid (HA)-modified chitosan nanoparticles (NPs).

Methods: RDN/TPD NPs were synthesized using the high- pressure homogenization – solvent evaporation technique. The fabricated NPs were then characterized and optimized for suitable physicochemical characteristics. The optimized NPs were then evaluated for bone remodeling potential via assessment of time-mannered modulation in proliferation, differentiation, and mineralization of osteoblasts.

Results: Results showed that HA-RDN/TPD NPs exhibited excellent physicochemical characteristics (nanoscopic size, stable zeta potential, high entrapment efficiency, and smooth spherical shape) and remained stable upon storage in the refrigerator. Assessment of various aspects of the cell growth cycle (i.e., proliferation, differentiation, and mineralization) evidenced promising bone regeneration efficacy of HA-RDN/TPD NPs.

Conclusion: This new strategy of employing simultaneous delivery of anti-resorptive and bone-forming agents would open new horizons for scientists, researchers, and healthcare providers as an efficient pharmacotherapy for the treatment of osteoporosis.

Keywords: Osteoporosis, hyaluronic acid, risedronate, teriparatide, nanotechnology, bone remodeling.

Sözen T, Özışık L, Başaran NC. An overview and management of osteoporosis. Eur J Rheumatol 2017; 4(1): 46-56.
[] [PMID: 28293453]
Pisani P, Renna MD, Conversano F, et al. Major osteoporotic fragility fractures: Risk factor updates and societal impact. World J Orthop 2016; 7(3): 171-81.
[] [PMID: 27004165]
Harvey NC, McCloskey EV, Mitchell PJ, et al. Mind the (treatment) gap: A global perspective on current and future strategies for prevention of fragility fractures. Osteoporos Int 2017; 28(5): 1507-29.
[] [PMID: 28175979]
Thu HE, Hussain Z, Mohamed IN, Shuid AN. Exploring dynamic biomedical algorithm of Eurycoma longifolia Jack and its bioactive phytochemicals: A review of pharmacokinetic and pharmacodynamic implications and future prospects. Asian Pac J Trop Med 2018; 11: 89-97.
Hussain Z, Arooj M, Malik A, et al. Nanomedicines as emerging platform for simultaneous delivery of cancer therapeutics: new developments in overcoming drug resistance and optimizing anticancer efficacy. Artif Cells Nanomed Biotechnol 2018; 46(Sup2): 1015-24.
[] [PMID: 29873531]
Hussain Z, Thu HE, Ng SF, Khan S, Katas H. Nanoencapsulation, an efficient and promising approach to maximize wound healing efficacy of curcumin: A review of new trends and state-of-the-art. Colloids Surf B Biointerfaces 2017; 150: 223-41.
[] [PMID: 27918967]
Hussain Z, Thu HE, Amjad MW, Hussain F, Ahmed TA, Khan S. Exploring recent developments to improve antioxidant, anti-inflammatory and antimicrobial efficacy of curcumin: A review of new trends and future perspectives. Mater Sci Eng C 2017; 77: 1316-26.
[] [PMID: 28532009]
Ahmed S, Govender T, Khan I, et al. Experimental and molecular modeling approach to optimize suitable polymers for fabrication of stable fluticasone nanoparticles with enhanced dissolution and antimicrobial activity. Drug Des Devel Ther 2018; 12: 255-69.
[] [PMID: 29440875]
Hussain Z, Katas H, Yan SL, Jamaludin D. Efficient colonic delivery of DsiRNA by pectin-coated polyelectrolyte complex nanoparticles: preparation, characterization and improved gastric survivability. Curr Drug Deliv 2017; 14(7): 1016-27.
[] [PMID: 28240178]
Md S, Kuldeep Singh JKA, Waqas M, et al. Nanoencapsulation of betamethasone valerate using high pressure homogenization-solvent evaporation technique: optimization of formulation and process parameters for efficient dermal targeting. Drug Dev Ind Pharm 2019; 45(2): 323-32.
[] [PMID: 30404554]
Ren B, Chen X, Du S, et al. Injectable polysaccharide hydrogel embedded with hydroxyapatite and calcium carbonate for drug delivery and bone tissue engineering. Int J Biol Macromol 2018; 118(Pt A): 1257-66.
Yang H, Gao H, Wang Y. Hollow hydroxyapatite microsphere: A promising carrier for bone tissue engineering. J Microencapsul 2016; 33(5): 421-6.
[] [PMID: 27357859]
Ali A, Ahmed S. A review on chitosan and its nanocomposites in drug delivery. Int J Biol Macromol 2018; 109: 273-86.
[] [PMID: 29248555]
Dong J, Tao L, Abourehab MAS, Hussain Z. Design and development of novel hyaluronate-modified nanoparticles for combo-delivery of curcumin and alendronate: fabrication, characterization, and cellular and molecular evidences of enhanced bone regeneration. Int J Biol Macromol 2018; 116: 1268-81.
[] [PMID: 29782984]
Zhuo F, Abourehab MAS, Hussain Z. Hyaluronic acid decorated tacrolimus-loaded nanoparticles: Efficient approach to maximize dermal targeting and anti-dermatitis efficacy. Carbohydr Polym 2018; 197: 478-89.
[] [PMID: 30007638]
Pandey M, Choudhury H, Gunasegaran TAP, et al. Hyaluronic acid-modified betamethasone encapsulated polymeric nanoparticles: fabrication, characterisation, in vitro release kinetics, and dermal targeting. Drug Deliv Transl Res 2019; 9(2): 520-33.
[] [PMID: 29488170]
Eriksen EF, Díez-Pérez A, Boonen S. Update on long-term treatment with bisphosphonates for postmenopausal osteoporosis: a systematic review. Bone 2014; 58: 126-35.
[] [PMID: 24120384]
Jensen PR, Andersen TL, Pennypacker BL, Duong LT, Delaissé JM. The bone resorption inhibitors odanacatib and alendronate affect post-osteoclastic events differently in ovariectomized rabbits. Calcif Tissue Int 2014; 94(2): 212-22.
[] [PMID: 24085265]
Lindsay R, Krege JH, Marin F, Jin L, Stepan JJ. Teriparatide for osteoporosis: importance of the full course. Osteoporos Int 2016; 27(8): 2395-410.
[] [PMID: 26902094]
Safdar MH, Hussain Z, Abourehab MAS, Hasan H, Afzal S, Thu HE. New developments and clinical transition of hyaluronic acid-based nanotherapeutics for treatment of cancer: reversing multidrug resistance, tumour-specific targetability and improved anticancer efficacy. Artif Cells Nanomed Biotechnol 2018; 46(8): 1967-80.
[PMID: 29082766]
Bukhari SNA, Hussain F, Thu HE, Hussain Z. Synergistic effects of combined therapy of curcumin and Fructus Ligustri Lucidi for treatment of osteoporosis: cellular and molecular evidence of enhanced bone formation. J Integr Med 2019; 17(1): 38-45.
[] [PMID: 30139656]
Chen LH, Xue JF, Zheng ZY, Shuhaidi M, Thu HE, Hussain Z. Hyaluronic acid, an efficient biomacromolecule for treatment of inflammatory skin and joint diseases: A review of recent developments and critical appraisal of preclinical and clinical investigations. Int J Biol Macromol 2018; 116: 572-84.
[] [PMID: 29772338]
Hussain Z, Thu HE, Katas H, Bukhari SNA. Hyaluronic acid-based biomaterials: A versatile and smart approach to tissue regeneration and treating traumatic, surgical, and chronic wounds. Polym Rev (Phila Pa) 2017; 57: 594-630.
Bukhari SNA, Roswandi NL, Waqas M, et al. Hyaluronic acid, a promising skin rejuvenating biomedicine: A review of recent updates and pre-clinical and clinical investigations on cosmetic and nutricosmetic effects. Int J Biol Macromol 2018; 120(Pt B): 1682-95.
[] [PMID: 30287361]
Hussain Z, Katas H, Mohd Amin MC, Kumolosasi E, Buang F, Sahudin S. Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone/hydroxytyrosol: An ex vivo and in vivo study using an NC/Nga mouse model. Int J Pharm 2013; 444(1-2): 109-19.
[] [PMID: 23337632]
Haliza K, Zahid H, Chai LT. Chitosan nanoparticles as a percutaneous drug delivery system for hydrocortisone. J Nanomater 2012; 372725: 11.
Thu HE, Mohamed IN, Hussain Z, Shuid AN. Eurycoma longifolia as a potential alternative to testosterone for the treatment of osteoporosis: Exploring time-mannered proliferative, differentiative and morphogenic modulation in osteoblasts. J Ethnopharmacol 2017; 195: 143-58.
[] [PMID: 27818256]
Thu HE, Mohamed IN, Hussain Z, Shuid AN. Exploring molecular mechanism of bone-forming capacity of Eurycoma longifolia: Evidence of enhanced expression of bone-related biomarkers. J Ayurveda Integr Med 2018; 9(4): 272-80.
[] [PMID: 29146110]
Yamakawa K, Iwasaki H, Masuda I, et al. The utility of alizarin red s staining in calcium pyrophosphate dihydrate crystal deposition disease. J Rheumatol 2003; 30(5): 1032-5.
[PMID: 12734902]
Sharma N, Madan P, Lin S. Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: A co-surfactant study. Asian J Pharma Sci 2016; 11: 404-16.
Bhattacharjee S. DLS and zeta potential-What they are and what they are not? J Control Release 2016; 235: 337-51.
[] [PMID: 27297779]
Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems - a review. Trop J Pharm Res 2013; 12(2): 255-64.
Jensen PR, Andersen TL, Pennypacker BL, Duong LT, Engelholm LH, Delaissé JM. A supra-cellular model for coupling of bone resorption to formation during remodeling: lessons from two bone resorption inhibitors affecting bone formation differently. Biochem Biophys Res Commun 2014; 443(2): 694-9.
[] [PMID: 24333871]
Abdelgawad ME, Søe K, Andersen TL, et al. Does collagen trigger the recruitment of osteoblasts into vacated bone resorption lacunae during bone remodeling? Bone 2014; 67: 181-8.
[] [PMID: 25019594]
Wang W, Olson D, Liang G, et al. Collagen XXIV (Col24α1) promotes osteoblastic differentiation and mineralization through TGF-β/Smads signaling pathway. Int J Biol Sci 2012; 8(10): 1310-22.
[] [PMID: 23139630]
Berli M, Borau C, Decco O, et al. Localized tissue mineralization regulated by bone remodelling: A computational approach. PLoS One 2017; 12(3)e0173228
[] [PMID: 28306746]
Liu DB, Sui C, Wu TT, Wu LZ, Zhu YY, Ren ZH. Association of Bone Morphogenetic Protein (BMP)/Smad signaling pathway with fracture healing and osteogenic ability in senile osteoporotic fracture in humans and rats. Med Sci Monit 2018; 24: 4363-71.
[] [PMID: 29938690]
Huang HM, Li XL, Tu SQ, Chen XF, Lu CC, Jiang LH. Effects of roughly focused extracorporeal shock waves therapy on the expressions of bone morphogenetic protein-2 and osteoprotegerin in osteoporotic fracture in rats. Chin Med J (Engl) 2016; 129(21): 2567-75.
[] [PMID: 27779163]
Martin A, Xiong J, Koromila T, et al. Estrogens antagonize RUNX2-mediated osteoblast-driven osteoclastogenesis through regulating RANKL membrane association. Bone 2015; 75: 96-104.
[] [PMID: 25701138]
Martin A, Yu J, Xiong J, et al. Estrogens and androgens inhibit association of RANKL with the pre-osteoblast membrane through post-translational mechanisms. J Cell Physiol 2017; 232(12): 3798-807.
[] [PMID: 28213978]
Singh S, Kumar D, Lal AK. Serum osteocalcin as a diagnostic biomarker for primary osteoporosis in women. J Clin Diagn Res 2015; 9(8): RC04-7.
[] [PMID: 26436008]

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