Original ArticleNovel osteoprotective nanocochleate formulation: A dual combination therapy-codelivery system against glucocorticoid induced osteoporosis
Graphical Abstract
Nanocochleate containing vitamin D3 was formulated efficiently with sustained-release behavior, improved bioavailability, and increased drug targeting. Interestingly, nanocochleate exhibited an anti-osteoporotic potentiation which acted better than alendronate as a standard drug in this study.
Section snippets
Chemicals
Phosphatidylserine was manufactured by Pharmin USA, LLC (USA). Sodium alendronate hydrate was purchased from Dr. Abidi Pharmaceutical Company, Tehran, Iran. Methylprednisolone sodium succinate (MP) was used as glucocorticoid and purchased from Pfizer Pharmaceuticals (USA). Amicon Ultra 10 kDa filter centrifuge tubes were purchased from EMD-Millipore (Billerica, USA).
Nanocochleate preparation and characterization
A modified method adapted from previous studies was applied to prepare Nanococh using nontoxic chemical agents.14,23
PS (200 mg)
Characterization and in vitro sustained release of Nanococh-D3
Particle size analysis of Nanococh-D3 showed that z-average size of nanocochleates was in the range of 319.4 ± 27.3 nm with a good polydispersity index of 0.38 ± 0.08 and surface charge of −11.8 ± 1.2 mV using DLS. The entrapment efficiency percentage was also estimated at a range of 98.2 ± 3.3 in Nanococh-D3 formulation as given in Figure 1. FESEM technique showed that the morphology of Nanococh subunits at high magnification was as rolled stacks dispersed in the submicron size range (Figure 1
Discussion
Cochleates containing phosphatidylserine are versatile carriers for advanced oral administration of active compounds against serious illnesses with reduced drug toxicity and increased drug efficacy.15., 16., 17., 18. Furthermore, due to their spirally rolled bilayer, highly stable Nanococh structures, they protect their cargo from destruction while producing long-lasting drug release in the circulation.26,27
In the current study, a role-shaped Nanococh containing vitamin D was produced in a size
Acknowledgments
This research has been supported by Tehran University of Medical Sciences and Health Services grant (No. 95-03-158-33113).
This research has been also financially sustained by Iran National Science Foundation grant (No. 95848872).
Authorship contribution
Maryam Eskandarynasab: Conceptualization, InvestigationWriting - original draft.
Shahroo Etemad-Moghadam: Formal analysis, Data curation.
Mojgan Alaeddini: Formal analysis, Data curation.
Amir Hossein Doustimotlagh: Methodology, Software.
Ali Nazeri: Methodology, Software.
Ahmad Reza Dehpour: Data validation, Visualization.
Ramin Goudarzi: Review & editing.
Alireza Partoazar: Supervision, Conseptualization, Methodology, Funding acquisition, Writing - review & editing,
References (50)
- et al.
Natural products for treatment of osteoporosis: the effects and mechanisms on promoting osteoblast-mediated bone formation
Life Sci
(2016) - et al.
Osteoporotic fractures in older adults
Best Pract Res Clin Rheumatol
(2006) - et al.
The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts
Bone
(2003) - et al.
Biocompatibility and osteogenesis of biomimetic bioglass-collagen-phosphatidylserine composite scaffolds for bone tissue engineering
Biomaterials
(2011) - et al.
Dispersion and stabilization of cochleate nanoparticles
Eur J Pharm Biopharm
(2017) - et al.
Relation of body fat indexes to vitamin D status and deficiency among obese adolescents
Am J Clin Nutr
(2009) - et al.
Effects of short-term treatment with prednisolone and calcitriol on bone and mineral metabolism in normal men
Bone
(1998) - et al.
Mechanotransduction in osteoblast regulation and bone disease
Trends Mol Med
(2009) - et al.
High dose dietary vitamin D3 increases bone mass and strength in mice
Bone Rep
(2017) - et al.
Risk of hip fracture according to the World Health Organization criteria for osteopenia and osteoporosis
Bone
(2000)
Molecular biology of bone remodeling: implications for new therapeutic targets for osteoporosis
Maturitas
Vitamin D analysis in plasma by high performance liquid chromatography (HPLC) with C30 reversed phase column and UV detection—easy and acetonitrile-free
J Chromatogr A
Improvement of bone microarchitecture in methylprednisolone induced rat model of osteoporosis by using thiolated chitosan-based risedronate mucoadhesive film
Drug Dev Ind Pharm
In-hospital care, complications, and 4-month mortality following a hip or proximal femur fracture: the Spanish registry of osteoporotic femur fractures prospective cohort study
Archives of osteoporosis
Mechanisms of glucocorticoid action in bone
Curr Osteoporos Rep
Bones and Crohn's. Risk factors associated with low bone mineral density in patients with Crohn's disease
Inflamm Bowel Dis
Novel regulation of 25-hydroxyvitamin D3 24-hydroxylase (24(OH)ase) transcription by glucocorticoids: cooperative effects of the glucocorticoid receptor, C/EBP beta, and the vitamin D receptor in 24(OH)ase transcription
J Cell Biochem
New insights into the mechanisms of vitamin D action
J Cell Biochem
Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy
J Cell Biochem
Risks and benefits of bisphosphonate therapies
J Cell Biochem
Screening for osteoporosis in postmenopausal women: recommendations and rationale
AJN The American Journal of Nursing
Understanding cochleate formation: insights into structural development
Soft Matter
Micro-spherical cochleate composites: method development for monodispersed cochleate system
J Liposome Res
Efficacy of a nanocochleate-encapsulated 3,5-diaryl-s-triazole derivative in a murine model of graft-versus-host disease
Transplantation
Efficacy of targeted liposomes and nanocochleates containing imatinib plus dexketoprofen against fibrosarcoma
Drug Dev Res
Cited by (6)
Nanocochleates: A potential drug delivery system
2021, Journal of Molecular LiquidsCitation Excerpt :Apart from this, vitamin D 3 nanocochleates improved bone strength same as in control group better than alendronate treatment. Thus this novel therapy will be better option to treat osteoporosis [35]. The higher level of low-density lipoprotein (LDL) and low level of high-density lipoproteins (HDL) are prime causes of atherosclerosis and other coronary heart diseases.
Application of bone alkaline phosphatase and 25-oxhydryl-vitamin D in diagnosis and prediction of osteoporotic vertebral compression fractures
2023, Journal of Orthopaedic Surgery and ResearchNanomedicine and regenerative medicine approaches in osteoarthritis therapy
2022, Aging Clinical and Experimental ResearchNovel nanohydroxyapatite (Nhap)-based scaffold doped with iron oxide nanoparticles (io), functionalized with small non-coding rna (mir-21/ 124) modulates expression of runt-related transcriptional factor 2 and osteopontin, promoting regeneration of osteoporotic bone in bilateral cranial defects in a senescence-accelerated mouse model (sam/p6). part 2
2021, International Journal of Nanomedicine
Conflict of interest: The authors confirm that they never have conflict of interest.