Design, Optimization and Characterization of Nanostructured Lipid Carriers of Raloxifene Hydrochloride for Transdermal Delivery

Author(s): Durga Puro, Rajani Athawale*, Anjali Pandya.

Journal Name: Nanoscience & Nanotechnology-Asia

Volume 10 , Issue 1 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Introduction: Raloxifene Hydrochloride (RXL), a BCS class II drug, is used for the treatment of invasive breast cancer and osteoporosis in post menopausal women. Even though the drug is highly efficient, it shows poor bioavailability of 2% when administered orally. The aim of the study was to develop, statistically optimize, and characterize Raloxifene Hydrochloride loaded Nanostructured Lipid Carriers (NLC) for transdermal delivery to overcome the bioavailability issue.

Methods: The RXL-NLC’s were developed using glyceryl behenate (Compritol® 888 ATO), glyceryl monostearate (GMS), and capric triglyceride (Miglyol® 810) as solid and liquid lipids, and Polysorbate 80 (Tween 80) and cremophor EL were used as surfactants and co-surfactant. A response surface methodology was applied for the optimization of NLC, using Box-Behnken experimental design. Amount of the drug, tween 80 and polyethoxylated castor oil (cremophor EL), each at three levels, were selected as independent variables, while particle size and polydispersity index were identified as dependent variables. The optimized batch was characterized for Particle size (79.8 nm±3), Polydispersity index (0.229±0.05), Zeta potential (-12.3±5) and Entrapment efficiency (79.14%±5). Surface morphology of the NLC’s were studied using Transmission Electron microscopy (TEM) and the shift in the endotherm of Differential scanning calorimetry confirmed the entrapment of the drug within NLC. In vitro drug release studies were performed using dialysis bag (12000-14000 Da) method. The optimized NLC dispersion was then incorporated into gel and characterized for gel uniformity, spreadability, pH, viscosity and drug content.

Results: In vivo skin penetration study was carried out by tape stripping method, which showed increase in penetration when incorporated into nanogel as compared to plain drug gel.

Conclusion: Based on the above result it can be concluded that transdermal delivery of NLC’s can be a superior alternative for orally low bioavailable drugs such as RXL which undergoes rapid first pass metabolism.

Keywords: Transdermal, Nanostructured Lipid Carriers (NLC), optimization, bioavailability, skeletal disease, osteoporosis.

Kanis, J.A. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO report. WHO Study Group. Osteoporos. Int., 1994, 4, 368-381.
Kanis, JA on behalf of the World Health Organization Scientific Group. Assessment of osteoporosis at the primary health care level. WHO scientific group Technical Report. 2007, 66.
Chlebowski, R.T.; Manson, J.E.; Anderson, G.L.; Cauley, J.A.; Aragaki, A.K.; Stefanick, M.L.; Lane, D.S.; Johnson, K.C.; Wactawski-Wende, J.; Chen, C.; Qi, L.; Yasmeen, S.; Newcomb, P.A.; Prentice, R.L. Estrogen plus Progestin and breast cancer incidence and mortality in women’s health initiative observational study. J. Natl. Cancer Inst., 2013, 105(8), 526-535.
Scalley, E.K.; Henrich, J.B. An overview of estrogen replacement therapy in postmenopausal women. J. Womens Health, 1993, 2, 289.
Witt, D.M.; Lousberg, T.R. Controversies surrounding estrogen use in postmenopausal women. Ann. Pharmacother., 1997, 31, 745.
Josse, R.G. clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. Can. Med. Assoc., 1996, 155, 929.
Bikiaris, D.; Karavelidis, V.; Karavas, E. Synthesis and application as drug carriers for the preparation of raloxifene HCL loaded nanoparticles. Molecules (Basel, Switzerland), 2009, 14(7), 2410-2430.
Sato, M.; Glasebrook, A.L.; Bryant, H.U. Raloxifene: A selective estrogen receptor modulator. J. Bone Miner. Metab., 1994, 12, S9-S20.
Paech, K.; Webb, D.; Kuiper, G.G. Differential ligand activation of strogen receptors E and ER at API sites. Science, 1997, 277, 1508-1510.
Buzdar, A.U.; Marcus, C.; Holmes, F.; Hug, V.; Hortobagyi, G. Phase II evaluation of Ly156758 in metastatic breast cancer. Oncology, 1988, 45(5), 344-345.
Jordan, V.C.; Phelps, E.; Lindgren, J.U. Effects of anti-estrogens on bone in castrated and intact female rats. Breast Cancer Res. Treat., 1987, 10(1), 31-35.
Black, L.J.; Sato, M.; Rowley, E.R. Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J. Clin. Invest., 1994, 93(1), 63-69.
Sato, M.; Kim, J.; Short, L.L.; Slemenda, C.W.; Bryant, H.U. Longitudinal and cross-sectional analysis of raloxifene effects on tibiae from ovariectomized aged rats. J. Pharmacol. Exp. Ther., 1995, 72(3), 1252-1259.
Wempe, M.F.; Wacher, V.J.; Ruble, K.M. Pharmacokinetics of raloxifene in male Wistar–Hannover rats: Influence of complexation with hydroxybutenyl-beta-cyclodextrin. Int. J. Pharm., 2008, 346, 25-37.
Heringa, M. Review on raloxifene: Profile of a selective estrogen receptor modulator. Int. J. Clin. Pharmacol. Ther., 2003, 41(8), 331-345.
Escobar-Chávez, J.J.; Rodríguez-Cruz, I.M.; Domínguez-Delgado, C.L.; Díaz-Torres, R.; Revilla-Vázquez, A.L.; Aléncaster, N.C. Nanocarrier systems for transdermal drug delivery.In: Recent advances in novel drug carrier systems; InTech: Rijeka, Croatia, 2012.
Bahiraei, M.; Hangi, M.; Saeedan, M. A novel application for energy efficiency improvement using nanofluid in shell and tube heat exchanger equipped with helical baffles. Energy, 2015, 93(2), 2229-2240.
Bahiraei, M.; Khosravi, R.; Heshmatian, S. Assessment and optimization of hydrothermal characteristics for a non-Newtonian nanofluid flow within miniaturized concentric-tube heat exchanger considering designer’s viewpoint. Appl. Therm. Eng., 2017, 123, 266-276.
Jo, S-H.; Kim, K-H.; Kim, Y-H.; Lee, M-H.; Kim, B-W.; Ahn, J-H. Deodorization of food-related nuisances from a refrigerator: The feasibility test of photocatalytic system. Chem. Eng. J., 2015, 277, 260-268.
Bahiraei, M.; Hangi, M.; Hosseinalipour, S. Numerical study and optimization of hydrothermal characteristics of Mn–Zn ferrite nanofluid within annulus in the presence of magnetic field. J. Supercond. Nov. Magn., 2014, 27(2), 527-534.
Robert, W.L.; Dinesh, B.S. Rajiv, Sheel. Micellar nanoparticles: Applications for topical and passive transdermal drug delivery.In: Handbook Non Invasive Drug Delivery Systems; Science Direct, 2010, pp. 37-58.
Mahmood, S.; Taher, M. Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application. Int. J. Nanomed, 2014, 9, 4331-4346.
Barry, B. Breaching the skin’s barrier to drugs. Nat. Biotechnol., 2004, 22(2), 165-167.
Mishra, S.; Kesharwani, R. Improvement of drug penetration through the skin by using nanostructured lipid carriers (NLC). Int. J. Pharm. Pharm. Res., 2016, 6(3), 481-496.
López-García, R.; Ganem-Rondero, A. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): Occlusive effect and penetration enhancement ability. J. Cosmetics Dermatol. Sci. Appl., 2015, 5, 62-72.
Prabhu, P.; Dubey, A.; Kamath, J.V. Nano Structured lipid carriers: A novel topical drug delivery system. Int. J. Pharm. Tech. Res., 2012, 4(2), 705-714.
Svilenov, H. solid lipid nanoparticles – a promising drug delivery system. Nanomedicine, 2011, 3(4), 187-237.
Shekhawat, P. Preparation and evaluation of clotrimazole Nanostructured lipid carrier for topical delivery. Int. J. Pharma Bio Sci., 2013, 4(1), 407-416.
Dandagi, P. Formulation and evaluation of nanostructured lipid carrier (nlc) of lornoxicam. Int. J. Pharm. Pharm. Sci., 2014, 6(2), 73-77.
Kushwaha, A.K. Development and evaluation of solid lipid nanoparticles of raloxifene hydrochloride for enhanced bioavailability. BioMed Res. Int., 2013, 2013584549
Klang, V.; Schwarz, J.C.; Lenobel, B.; Nadj, M.; Auböck, J.; Wolzt, M.; Valenta, C. In vitro vs. in vivo tape stripping: Validation of the porcine ear model and penetration assessment of novel sucrose stearate emulsions. Eur. J. Pharm. Biopharm., 2012, 80, 604-614.
Vaddi, H.K.; Ho, P.C.; Chan, S. Terpenes in propylene glycol as skin penetration enhancers: Permeation and partition of haloperidol, fourier transform infrared spectroscopy, and differential scanning calorimetry. J. Pharm. Sci., 2002, 91(7), 1639-1651.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [57 - 67]
Pages: 11
DOI: 10.2174/2210681208666181106124337
Price: $25

Article Metrics

PDF: 10