Metformin hydrochloride laden nanostructured lipid carriers
A promising strategy for skin diseases
DOI:
https://doi.org/10.1590/Keywords:
Lipid nanoparticles, Nanostructured lipid carriers (NLCs), Metformin Hydrochloride, Molecular docking, Factorial designAbstract
Metformin hydrochloride (MTF) has pharmacological properties for managing inflammatory skin conditions. MTF is a hydrophilic medication. Accordingly, embedding MTF into lipid carriers for enhancing skin penetration presents a challenge. The study aims to optimize the loading of MTF into nanostructured lipid carriers (NLCs) using a 22 full factorial design, employing the solvent injection technique. The NLCs were evaluated for encapsulation efficiency, hydrodynamic diameter, zeta potential, and polydispersity index. Alkalinization of the aqueous phase (pH = 12.5) resulted in maximizing the entrapment of MTF within NLCs. Furthermore, the tested solid lipids impacted the encapsulation of MTF based on their hydrophilic-lipophilic balance. The optimized formulation is composed of a lipid phase incorporating beeswax (75 mg), oleic acid (25 mg), and Span 60 (1% w/w), and an aqueous phase comprised of 1% w/w Tween 80, pH 12.5. The selected formula attained an entrapment efficiency of 53.68 ± 0.27%, a particle size of 333.0 ± 6.4 nm, and a negative surface charge, indicating adequate particles` stability. DSC and Molecular docking analyses confirmed the MTF incorporation within the lipid phase. The outcomes emphasize the importance of optimizing investigations in developing a viable delivery system for MTF to boost its permeation across the skin layers.
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Abdel-Rahman MA, El-Said WA, Sayed EM, Abdel-Wahab A-MA. Synthesis, characterization of some conductive aromatic polyamides/Fe3O4 NPs/ITO, and their utilization for methotrexate sensing. Surfaces. 2023;6:83-96.
Acebedo-Martínez FJ, Domínguez-Martín A, Alarcón-Payer C, Garcés-Bastida C, Verdugo-Escamilla C, Gómez-Morales J, et al. Metformin-NSAIDs molecular salts: A path towards enhanced oral bioavailability and stability. Pharmaceutics. 2023;15.
Agarwal R, Katare OP, Vyas SP. Preparation and in vitro evaluation of liposomal/niosomal delivery systems for antipsoriatic drug dithranol. Int J Pharm. 2001;228:43-52.
Albasri OWA, Kumar PV, Rajagopal MS. Development of Computational In Silico Model for Nano Lipid Carrier Formulation of Curcumin. Molecules. 2023;28:1833.
Álvarez-Trabado J, Diebold Y, Sanchez A. Designing lipid nanoparticles for topical ocular drug delivery. Int J Pharm . 2017;532(1):204-217.
Angelova MI, Bitbol AF, Seigneuret M, Staneva G, Kodama A, Sakuma Y, et al. pH sensing by lipids in membranes: The fundamentals of pH-driven migration, polarization and deformations of lipid bilayer assemblies. Biochim Biophys Acta Biomembr. 2018;1860:2042-2063.
Battaglia L, Gallarate M. Lipid nanoparticles: state of the art, new preparation methods and challenges in drug delivery. Expert Opin Drug Delivery. 2012;9:497-508.
Bawazeer S, El-Telbany DFA, Al-Sawahli MM, Zayed G, Keed AAA, Abdelaziz AE, et al. Effect of nanostructured lipid carriers on transdermal delivery of tenoxicam in irradiated rats. Drug Delivery. 2020;27:1218-1230.
Bos JD, Meinardi MM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000; Viewpoint 9;165-169.
Brubach JB, Jannin V, Mahler B, Bourgaux C, Lessieur P, Roy P, et al. Structural and thermal characterization of glyceryl behenate by X-ray diffraction coupled to differential calorimetry and infrared spectroscopy. Int J Pharm . 2007;336:248-256.
Chang J-E, Choi MS. A molecular perspective on the potential benefits of metformin for the treatment of inflammatory skin disorders. Int J Mol Sci. 2020;21:8960-8972.
Charoenputtakun P, Li SK, Ngawhirunpat T. Iontophoretic delivery of lipophilic and hydrophilic drugs from lipid nanoparticles across human skin. Int J Pharm . 2015;495:318-328.
Clogston JD, Patri AK. Zeta potential measurement. Characterization of nanoparticles intended for drug delivery. 2011;63-70.
Cohen-Sela E, Chorny M, Koroukhov N, Danenberg HD, Golomb G. A new double emulsion solvent diffusion technique for encapsulating hydrophilic molecules in PLGA nanoparticles. JCR. 2009;133:90-95.
Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10.
Devani M, Ashford M, Craig DQM. The emulsification and solubilisation properties of polyglycolysed oils in self-emulsifying formulations. JPP. 2010;56:307-316.
Eleraky NE, Omar MM, Mahmoud HA, Abou-Taleb HA. nanostructured lipid carriers to mediate brain delivery of temazepam: Design and in vivo study. Pharmaceutics. 2020;12(5):451.
El-Ridy MS, Yehia SA, Elsayed I, Younis MM, Abdel-Rahman RF, El-Gamil MA. Metformin hydrochloride and wound healing: from nanoformulation to pharmacological evaluation. J Liposome Res. 2019;29:343-356.
Elbahwy IA, Ibrahim HM, Ismael HR, Kasem AA. Enhancing bioavailability and controlling the release of glibenclamide from optimized solid lipid nanoparticles. J Drug Delivery Sci Technol. 2017;38:78-89.
Gomaa E, Fathi HA, Eissa NG, Elsabahy M. Methods for preparation of nanostructured lipid carriers. Methods. 2022;199:3-8.
Gordillo-Galeano A, Mora-Huertas CE. Hydrodynamic diameter and zeta potential of nanostructured lipid carriers: Emphasizing some parameters for correct measurements. Colloids Surf A. 2021;620:126610-126620.
Goyal R, Macri LK, Kaplan HM, Kohn J. Nanoparticles and nanofibers for topical drug delivery. JCR. 2016;240:77-92.
Hassan A. Assignment of Optimum Surfactants Blend and Right Oil Phase Concentration of Oil-in-water Emulsion. Indian J Pharm Sci. 2018;80:334-341.
Houacine C, Adams D, Singh KK. Impact of liquid lipid on development and stability of trimyristin nanostructured lipid carriers for oral delivery of resveratrol. J Mol Liq. 2020;316:113734-113752.
Joshi DR, Adhikari N. An overview on common organic solvents and their toxicity. J Pharm Res Int. 2019;28:1-18.
Joshi SA, Jalalpure SS, Kempwade AA, Peram MR. Fabrication and in-vivo evaluation of lipid nanocarriers based transdermal patch of colchicine. J Drug Deliv Technol. 2017;41:444-453.
Kenechukwu FC, Isaac GT, Nnamani DO, Momoh MA, Attama AA. Enhanced circulation longevity and pharmacodynamics of metformin from surface-modified nanostructured lipid carriers based on solidified reverse micellar solutions. Heliyon. 2022;8:e09100.
Khalil R, Hashem F, Zaki H, El-Arini S. Polymeric nanoparticles as potential carriers for topical delivery of colchicine: development and in vitro characterization. Int J Pharm Sci Res. 2014;5:1746-1756.
Kiss E, Berkó S, Gácsi A, Kovács A, Katona G, Soós J, et al. Design and optimization of nanostructured lipid carrier containing dexamethasone for ophthalmic use. Pharmaceutics. 2019;11:679-696.
Lademann J, Richter H, Schanzer S, Knorr F, Meinke M, Sterry W, et al. Penetration and storage of particles in human skin: Perspectives and safety aspects. Eur J Pharm Biopharm. 2011; 77; 465-468.
Leo E, Brina B, Forni F, Vandelli MA. In vitro evaluation of PLA nanoparticles containing a lipophilic drug in water-soluble or insoluble form. Int J Pharm . 2004;278:133-141.
Liu D, Zhang Y, Jiang G, Yu W, Xu B, Zhu J. Fabrication of dissolving microneedles with thermal-responsive coating for NIR-triggered transdermal delivery of metformin on diabetic rats. ACS Biomater Sci Eng. 2018;4:1687-1695.
Mady OY, Al-Shoubki AA, Donia AA. An industrial procedure for pharmacodynamic improvement of metformin HCl via granulation with its paracellular pathway enhancer using factorial experimental design. Drug Des Devel Ther. 2021;4469-4487.
Matkin J, Wang S, Li C, Huang W. Natural mixture of long-chain fatty alcohols and long-chain fatty acids, its obtension from animal and vegetable waxes and its nutraceutical uses. Google Patents. 2006.
Mendes IT, Ruela ALM, Carvalho FC, Freitas JTJ, Bonfilio R, Pereira GR. Development and characterization of nanostructured lipid carrier-based gels for the transdermal delivery of donepezil. Colloids Surf B. 2019;177:274-281.
Metry M, Shu Y, Abrahamsson B, Cristofoletti R, Dressman JB, Groot D, et al. Biowaiver monographs for immediate release solid oral dosage forms: metformin hydrochloride. J Pharm Sci. 2021;110:1513-1526.
Moghadam H, Zakeri M, Samimi A. Mono-Size Distribution Index (MSDI): A new criterion for the quantitative description of size distribution. JPST. 2019;5:71-76.
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009;30:2785-2791.
Negi LM, Jaggi M, Talegaonkar S. Development of protocol for screening the formulation components and the assessment of common quality problems of nano-structured lipid carriers. Int J Pharm . 2014;461:403-410.
Rizwanullah M, Amin S, Ahmad J. Improved pharmacokinetics and antihyperlipidemic efficacy of rosuvastatin-loaded nanostructured lipid carriers. J Drug Targeting. 2017;25:58-74.
Rostamkalaei SS, Akbari J, Saeedi M, Morteza-Semnani K, Nokhodchi A. Topical gel of Metformin solid lipid nanoparticles: A hopeful promise as a dermal delivery system. Colloids Surf B . 2019;175:150-157.
Saeed HK, Sutar Y, Patel P, Bhat R, Mallick S, Hatada AE, et al. Synthesis and characterization of lipophilic salts of metformin to improve its repurposing for cancer therapy. ACS Omega. 2021;6;2626-2637.
Salem HF, Nafady MM, Ali AA, Khalil NM, Elsisi AA. Evaluation of metformin hydrochloride tailoring bilosomes as an effective transdermal nanocarrier. Int J Nanomed. 2022;1185-1201.
Sharma A, Baldi A. Nanostructured lipid carriers: A review. J Dev Drugs. 2018;7:1-15.
Sharma P, Ganta S, Denny WA, Garg S. Formulation and pharmacokinetics of lipid nanoparticles of a chemically sensitive nitrogen mustard derivative: Chlorambucil. Int J Pharm . 2009;367:187-194.
Shete MB, Deshpande AS, Shende PK. Nanostructured lipid carrier-loaded metformin hydrochloride: Design, optimization, characterization, assessment of cytotoxicity and ROS evaluation. Chem Phys Lipids. 2023;250:105256.
Shi L, Li Z, Yu L, Jia H, Zheng L. Effects of Surfactants and Lipids on the Preparation of Solid Lipid Nanoparticles Using Double Emulsion Method. J Disper Sci Technol. 2011;32:254-259.
Stanescu AMA, Simionescu AA, Florea M, Diaconu CC. Is Metformin a Possible Beneficial Treatment for Psoriasis? A Scoping Review. J Pers Med. 2021;11.
Swarnakar NK, Thanki K, Jain S. Bicontinuous cubic liquid crystalline nanoparticles for oral delivery of Doxorubicin: implications on bioavailability, therapeutic efficacy, and cardiotoxicity. Pharm Res. 2014;31:1219-1238.
Swidan SA, Ghonaim HM, Samy AM, Ghorab MM. Efficacy and in vitro cytotoxicity of nanostructured lipid carriers for paclitaxel delivery. J Appl Pharm Sci. 2016;6:018-026.
Tekko IA, Permana AD, Vora L, Hatahet T, McCarthy HO, Donnelly RF. Localised and sustained intradermal delivery of methotrexate using nanocrystal-loaded microneedle arrays: Potential for enhanced treatment of psoriasis. Eur J Pharm Sci . 2020;152:105469.
Xu Q, Zhu T, Yi C, Shen Q. Characterization and evaluation of metformin-loaded solid lipid nanoparticles for celluar and mitochondrial uptake. Drug Dev Ind Pharm. 2016;42:701-706.
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