OPTIMIZATION AND CHARACTERIZATION OF DOXORUBICIN LOADED SOLID LIPID NANOSUSPENSION FOR NOSE TO BRAIN DELIVERY USING DESIGN EXPERT SOFTWARE
DOI:
https://doi.org/10.22159/ijpps.2021v13i5.41137Keywords:
Solid lipid Nanosuspension, Homogenization and Ultrasonication, Characterization, Factorial design, Nose to brain deliveryAbstract
Objective: The goal of the current study was to investigate the possible use of solid lipid nanosuspension (SLNs) as a drug delivery method to boost doxorubicin (DOX) brain-targeting performance after intranasal (i. n.) administration.
Methods: 33 factorial design was applied for optimization by using lipid concentration, surfactant concentration, and High-speed homogenizer (HSH) stirring time as dependent variables, and their effect was observed on particles size, Polydispersity index (PDI), and entrapment efficiency.
Results: With the composition of Compritol® 888 ATO (4.6 % w/v), tween 80 (1.9 % w/v), and HSH stirring time, the optimized formula DOX-SLNs prepared (10 min). Particle size, PDI, zeta potential, entrapment efficiency, percent in vitro release were found to be 167.47±6.09 nm, 0.23±0.02, 24.1 mV, 75.3±2.79, and 89.35±3.27 percent in 24 h, respectively, for optimized formulation (V-O). No major changes in particle size, zeta potential, and entrapping efficiency were found in the stability studies at 4±2 °C (refrigerator) and 25±2 °C/60±5% RH up to 3 mo.
Conclusion: Following the non-invasive nose-to-brain drug delivery, which is a promising therapeutic strategy, the positive findings confirmed the current optimized DOX-loaded SLNs formulation.
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Zubareva A, Shcherbinina T, Varlamov VP, Svirshchevskaya E. Biodistribution of doxorubicin-loaded succinyl chitosan nanoparticles in mice injected via intravenous or intranasal routes. PCACD 2014;19:145-54.
Mussi V, Silva C. New approach to improve encapsulation and antitumor activity of doxorubicin-loaded in solid lipid nanoparticles. Eur J Pharm Sci 2013;48:282-90.
Oliveira S, Mussi V. α-Tocopherol succinate improves encapsulation and anticancer activity of doxorubicin-loaded in solid lipid nanoparticles. Colloids Surf B 2016;140:246-53.
Lala RR, Shinde AS, Nandvikar NY. Solid lipid nanoparticles: a promising approach for combinational drug therapy in cancer. Int J Appl Pharm 2018;10:17-22.
Xiong P, Ding A, Su Z, Shen G, Chen Y, Zhang S. The efficacy and hyperthermic release of doxorubicin from liposomal doxorubicin hydrochloride in rabbits VX2 tumors. Int J Hyperthermia 2015;31:900-8.
Khatak S, Dureja H. Structural composition of solid lipid nanoparticles for invasive and non-invasive drug delivery. Curr Nanomaterials 2017;2:129-53.
Patel S, Chavhan S. Brain targeting of risperidone-loaded solid lipid nanoparticles by the intranasal route. J Drug Target 2011;19:468-74.
Shah M, Pathak K. Development and statistical optimization of solid lipid nanoparticles of simvastatin by using 23 full-factorial design. AAPS PharmSciTech 2010;11:489-96.
Gambhire S, Bhalekar R, Gambhire M. Statistical optimization of dithranol-loaded solid lipid nanoparticles using factorial design. Braz J Pharm Sci 2011;47:503-11.
Yasir M, Sara S. Solid lipid nanoparticles for a nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation. Acta Pharm Sin B 2014;4:454-63.
Bilati U, Allemann E, Doelker E. Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles. Eur J Pharm Sci 2005;25:67-75.
Dong Y, Ng W, Shen S, Kim S, Tan K. Solid lipid nanoparticles: continuous and potential large-scale nanoprecipitation production in static mixers. Colloids Surf B 2012;94:68-72.
Costa P, Lobo S. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001;13:123-33.
Gan L, Gao YP, Zhu CL. Novel pH-sensitive lipid-polymer composite microspheres of 10-hydroxycamptothecin exhibiting colon-specific biodistribution and reduced systemic absorption. J Pharm Sci 2013;102:1752-9.
Blasi P, Giovagnoli S, Schoubben A. Lipid nanoparticles for brain targeting formulation optimization. Int J Pharm 2011;419:287-95.
Bose S, Du Y, Takhistov P, Michniak Kohn B. Formulation optimization and topical delivery of quercetin from solid lipid-based nanosystems. Int J Pharm 2013;441:56-66.
Rajkumar M, Bhise B. Carbamazepine-loaded porous microspheres for short-term sustained drug delivery. J Young Pharm 2010;2:7-14.
Rahman Z, Zidan S, Khan A. Non-destructive methods of characterization of risperidone solid lipid nanoparticles. Eur J Pharm Biopharm 2010;76:127-37.
Borgia L, Regehly M, Sivaramakrishnan R. Lipid nanoparticles for skin penetration enhancement-correlation to drug localization within the particle-matrix as determined by fluorescence and parelectric spectroscopy. J Controlled Release 2005;110:151-63.
Cai S, Yang Q, Bagby R, Forrest L. Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles. Adv Drug Delivery Rev 2011;10:901-8.
Sarkar T, Ahmed B. Development and in vitro characterization of chitosan loaded paclitaxel nanoparticle. Asian J Pharm Clin Res 2016;9:145-8.
Hooda A, Nanda M, Jain V, Kumar P, Rathee. Optimization and evaluation of gastroretentive ranitidine HCl microspheres by using design expert software. Int J Biol Macromol 2012;51:691–700.
Mahajan A, Kaur S. Design, formulation, and characterization of stearic acid-based solid lipid nanoparticles of candesartan cilexetil to augment its oral bioavailability. Asian J Pharm Clin Res 2018;11:344-50.
Malakar J, Nayak K, Pal D. Development of cloxacillin loaded multiple-unit alginate-based floating system by an emulsion-gelation method. Int J Biol Macromol 2012;50:138–47.
Reddy H, Murthy R. Etoposide-loaded nanoparticles made from glyceride lipids: formulation, characterization, in vitro drug release, and stability evaluation. AAPS PharmSciTech 2005;6:158-66.
Thakkar P, Desai L, Parmar P. Application of Box-Behnken design for optimization of formulation parameters for nanostructured lipid carriers of candesartan cilexetil. Asian J Pharm 2014;8:81-9.
Shah M, Pathak K. Development and statistical optimization of solid lipid nanoparticles of simvastatin by using 23 full-factorial design. AAPS PharmSciTech 2010;11:489-96.
Subedi K, Kang W, Choi K. Preparation and characterization of solid lipid nanoparticles loaded with doxorubicin. Eur J Pharm Sci 2009;37:508-13.
Zhuang Y, Li N, Wang M. Preparation and characterization of vinpocetine loaded nanostructured lipid carriers (NLC) for improved oral bioavailability. Int J Pharm 2010;394:179–85.
Abdelbary G, Fahmy H. Diazepam-loaded solid lipid nanoparticles: design and characterization. AAPS PharmSciTech 2009;10:211-9.
Arora P, Sharma S, Garg S. Permeability issues in nasal drug delivery. Drug Discovery Today 2002;7:967-75.
Furubayashi T, Inoue D, Kamaguchi A, Higashi Y, Sakane T. Influence of formulation viscosity on drug absorption following nasal application in rats. Drug Metab Pharmacokinet 2007;22:206-11.
Joshi S, Patel S, Belgamwar S. Solid lipid nanoparticles of ondansetron HCl for intranasal delivery: development, optimization, and evaluation. J Mater Sci Mater Med 2012;23:2163–75.
Shazly A. Ciprofloxacin controlled-solid lipid nanoparticles: characterization, in vitro release, and antibacterial activity assessment. BioMed Res Int 2017;2017:1-9.
Aher S, Malsane T, Saudagar R. Nanosuspension: an overview. Int J Curr Pharm Res 2017;9:19-23.
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