• RAMANDEEP KAUR Centre for Pharmaceutical Sciences, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad (JNTUH), Hyderabad, Telangana State, India
  • Makula Ajitha Centre for Pharmaceutical Sciences, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad (JNTUH), Hyderabad, Telangana State, India


Objective: In the present study, transdermal nanoemulsion (NE) gel of lovastatin was investigated for its anti-osteoporosis effect on the long bones of rat i.e. tibia.

Methods: Male wistar rats (n=30, weighing 180-200g) were taken for this study and grouped as: 1) control (normal saline daily), 2) Dex (dexamethasone sodium; 25 mg/kg subcutaneously twice a week), 3) Dex+LNG5 (lovastatin nanoemulsion gel; 5 mg/kg/d transdermally daily), 4) Dex+LNG10 (lovastatin nanoemulsion gel; 10 mg/kg/d transdermally daily), and 5) Dex+ALN (alendronate sodium; 0.03 mg/kg/d orally daily). All the treatments were carried out for 60 d. At the end of the experiment, all animals were anesthetized using diethyl ether and collected blood samples from retro-orbital venous plexus of rats in dry eppendorf tubes followed by the sacrifice of animals by cervical dislocation method and collected tibia bones of both the legs for analysis.

Results: Bone formation biomarkers (OC: osteocalcin, b-ALP: bone-specific alkaline phosphatase, PINP: N-terminal propeptides of type I procollagen) were significantly improved and resorption biomarkers (CTx: C-terminal cross-linking telopeptides of type-I collagen, TRAcP5b: isoform 5b of tartarate resistant acid phosphatase) were significantly reduced in the LNG5 (p<0.05) and LNG10 (p<0.05) treatment groups when compared to Dex. In vivo anti-osteoporotic results demonstrated the formation of new bone in osteoporotic rat tibias. Biomechanical strength testing demonstrated increased load-bearing capacity of rat tibias in the treated animals in comparison with the osteoporotic group (p<0.05 for LNG5 and p<0.01 for LNG10).

Conclusion: Thus, the transdermal NE gel formulation of lovastatin demonstrated the greater potential for the treatment of osteoporosis.

Keywords: Nanoemulsion gel, Lovastatin, Bone biomarkers, Micro-CT, Bone mineral density, Biomechanical strength testing


Download data is not yet available.


1. Deal C. Potential new drug targets for osteoporosis. Nat Clin Pract Rheumatol 2009;5:20–7.
2. Sadat Ali M, Alelq AH, Alshafei BA, Al Turki HA, Abujubara MA. Osteoporosis prophylaxis in patients receiving chronic glucocorticoid therapy. Ann Saudi Med 2009;29:215–8.
3. Migliaccio S, Brama M, Fornari R, Greco EA, Spera G, Malavolta N. Glucocorticoidinduced osteoporosis: an osteoblastic disease. Aging Clin Exp Res 2007;19:5–10.
4. Lane NE, Yao W. Glucocorticoid-induced bone fragility. Ann N Y Acad Sci 2010;1192:81–3.
5. Ferrari P. Cortisol and the renal handling of electrolytes: role in glucocorticoid-induced hypertension and bone disease. Best Pract Res Clin Endocrinol Metab 2003;17:575–89.
6. Ahmeda HH, Morcosb NYS, Eskandera EF, Seoudib DMS, Shalbya AB. Role of dehydroepiandrosterone in management of glucocorticoid-induced secondary osteoporosis in female rats. Exp Toxicol Pathol 2012;64:659–64.
7. Honig S, Rajapakse CS, Chang G. Current treatment approaches to osteoporosis. Bull Hosp Jt Dis 2013;71:184-8.
8. Khajuria DK, Razdan R, Mahapatra DR. Drugs for the management of osteoporosis: a review. Rev Bras Reumatol 2011;51:365-82.
9. Mundy GR. Statins and their potential for osteoporosis. Bone 2001;29:495–7.
10. Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, et al. Stimulation of Bone Formation in vitro and in rodents by statins. Science 1999;286:1946-9.
11. Ruan F, Zheng Q, Wang J. Mechanisms of bone anabolism regulated by statins. Biosci Rep 2012;32:511–9.
12. Zhang Y, Bradley AD, Wang D, Reinhardt RA. Statins, bone metabolism and treatment of bone catabolic diseases. Pharmacol Res 2014;88:53-61.
13. Haberstadt C, Anderson P, Bartel R, Cohen R, Naughton G. Physiological cultured skin substitutes for wound healing. Mater Res Soc Symp Proc 1992;252:323–30.
14. Masuzaki T, Ayukawa Y, Moriyama Y, Jinno Y, Atsuta I, Ogino Y, et al. The effect of a single remote injection of statin-impregnated poly (lactic-co-glycolic acid) microspheres on osteogenesis around titanium implants in rat tibia. Biomaterials 2010;31:3327–34.
15. Zou Y, Brooks JL, Talwalkar V, Milbrandt TA, Puleo DA. Development of an injectable two-phase drug delivery system for sequential release of antiresorptive and osteogenic drugs. J Biomed Mater Res B Appl Biomater 2012;100:155-62.
16. Xiangning L, Xiaoran L, Shaobing L, Xiaosong Z, Sha L, Qiangbin W. An In vitro Study of a titanium surface modified by simvastatin-loaded titania nanotubes-micelles. J Biomed Nanotechnol 2014;10:194-204.
17. Stadlinger P, Korn N, Tödtmann U, Eckelt U, Range A, Bürki SJ, et al. Osseointegration of biochemically modified implants in an osteoporosis rodent model. Eur Cells Mater 2013;25:326-40.
18. Yoshii T, Hafeman AE, Nyman JS, Esparza JM, Shinomiya K, Spengler DM, et al. A sustained release of lovastatin from biodegradable, elastomeric polyurethane scaffolds for enhanced bone regeneration. Tissue Eng Part A 2010;16:236979.
19. Chou J, Ito T, Bishop D, Otsuka M, Ben-Nissan B. Controlled release of simvastatin from biomimetic b-TCP drug delivery system. PLoS ONE 2013;8:e54676
20. Park YS, David AE, Park KM, Lin C, Than KD, Lee K, et al. Controlled release of simvastatin from in situ forming hydrogel triggers bone formation in MC3T3-E1 cells. AAPS J 2013;15:367-76.
21. Tanabe K, Nomoto H, Okumori N, Miura T, Yoshinari M. Osteogenic effect of fluvastatin combined with biodegradable gelatin hydrogel. Dent Mater J 2012;31:489–93.
22. Kaur R, Ajitha M. Formulation of transdermal nanoemulsion gel drug delivery system of lovastatin and its in vivo characterization in glucocorticoid-induced osteoporosis rat model. J Drug Delivery Sci-Tech 2019;52:968-78.
23. Kaur R, Ajitha M. Transdermal delivery of fluvastatin loaded nanoemulsion gel: preparation, characterization and in vivo anti-osteoporosis activity. Eur J Pharm Sci 2019;136:104956.
24. El-Leithy ES, Makky AM, Khattab AM, Hussein DG. Nanoemulsion gel of nutraceutical co-enzyme q10 as an alternative to the conventional topical delivery system to enhance skin permeability and anti-wrinkle efficiency. Int J Pharm Pharm Sci 2017;9:207-1.
25. Vesper EO, Hammond MA, Allen MR, Wallace JM. Even with rehydration, preservation in ethanol influences the mechanical properties of bone and how bone responds to experimental manipulation. Bone 2017;97:49–53.
26. Bitto A, Burnett BP, Polito F, Levy RM, Marini H, Stefano VD, et al. Genistein aglycone reverses glucocorticoid-induced osteoporosis and increases bone breaking strength in rats: a comparative study with alendronate. Br J Pharmacol 2009;156:1287–95.
27. Campbell GM, Sophocleous A. Quantitative analysis of bone and soft tissue by micro-computed tomography: applications to ex vivo and in vivo studies. Bone key Rep 2014;3:564.
28. Oksztulska Kolanek E, Znorko B, Micha?owska M, Pawlak K. The biomechanical testing for the assessment of bone quality in an experimental model of chronic kidney disease. Nephron 2016;132:51-8.
29. Joy A, Chaitra N, Ashok M, Handral M. Antiosteoporotic activity of anthraquinone isolated from morinda citrifolia fruits in rats. Asian J Pharm Clin Res 2016;9:209-13.
30. Greenblatt MB, Tsai JN, Wein MN. Bone turnover markers in the diagnosis and monitoring of metabolic bone disease. Clin Chem 2017;63:464–74.
279 Views | 220 Downloads
How to Cite
KAUR, R., and M. Ajitha. “EFFECT OF LOVASTATIN NANO DRUG DELIVERY SYSTEM ON BONE MINERAL DENSITY (BMD) AND BIOMECHANICAL PROPERTIES OF TIBIA BONES OF WISTAR RATS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 11, no. 9, Sept. 2019, pp. 42-48, doi:10.22159/ijpps.2019v11i9.34624.
Original Article(s)