Formulation and Evaluation of a Multi-Active Nano-Lipid Hydrogel (MALA Nano-Gel) for Enhanced Topical Delivery of Depigmenting Agents in Melasma Management

Author

Hardik Joshi, Anirudh Singh Deora

Abstract

 Background: Melasma is a chronic, relapsing hyperpigmentation disorder characterised by inadequate response to conventional topical monotherapy due to poor skin penetration, active instability, and single-pathway targeting. Objective: To formulate, optimise, and evaluate a multi-active nano-lipid hydrogel (MALA Nano-Gel) incorporating tranexamic acid, niacinamide, alpha arbutin, azelaic acid, and ascorbyl glucoside in a lipid nanocarrier–Carbopol 980 hybrid matrix for enhanced topical delivery in melasma. Methods: MALA Nano-Gel was prepared by probe sonication of a lipid phase (soya lecithin, Tween 80, botanical oil blend) followed by dispersion in a Carbopol 980/Sepiplus-400 hydrogel. The optimised formulation was characterised for physicochemical properties (pH, spreadability, viscosity, rheology), nano-characteristics (DLS particle size, PDI, zeta potential), morphology (TEM, Cryo-SEM), solid-state properties (FTIR, XRD), in vitro drug release kinetics, ex vivo skin penetration (IVIS imaging, confocal laser scanning microscopy), and accelerated stability. Results: The optimised formulation exhibited a particle size of 168.5 ± 3.4 nm, PDI of 0.214 ± 0.018, zeta potential of −32.6 ± 1.8 mV, and a skin-compatible pH of 5.62 ± 0.08. TEM confirmed spherical nanoparticles (145.8 ± 5.4 nm); Cryo-SEM revealed an interconnected porous hydrogel network. FTIR confirmed drug–excipient compatibility; XRD demonstrated conversion of actives to a partially amorphous state. Cumulative drug release was 94.2 ± 3.5% over 24 h, following Korsmeyer–Peppas anomalous transport kinetics (n = 0.68, R² = 0.994). IVIS imaging showed a 1.55-fold higher radiant efficiency than the best-performing marketed formulation. Confocal Z-stack microscopy demonstrated a maximum penetration depth of 82.6 ± 4.3 µm, significantly exceeding Marketed Formulation A (46.2 ± 3.1 µm; p < 0.001) and Marketed Formulation B (62.3 ± 3.8 µm; p < 0.001). Formulation remained physically and chemically stable over three months under accelerated conditions. Conclusions: MALA Nano-Gel represents a promising, stable, multi-mechanistic topical delivery system with significantly superior skin penetration and retention compared with marketed products, supporting its potential as an advanced treatment for melasma.

Keywords

Melasma; Nano-lipid hydrogel; Tranexamic acid; Niacinamide; Topical drug delivery; Skin penetration; CLSM; IVIS imaging; Carbopol; Depigmentation

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References

[1] Kwon SH, Na JI, Choi JY, Park KC. Melasma: updates and perspectives. Exp Dermatol. 2016;25(1):11–15. https://doi.org/10.1111/exd.12811

[2] Handel AC, Miot LDB, Miot HA. Melasma: a clinical and epidemiological review. An Bras Dermatol. 2014;89(5):771–782. https://doi.org/10.1590/abd1806-4841.20143063

[3] Cestari T, Arellano I, Hexsel D, Ortonne JP. Melasma in Latin America: options for therapy and treatment algorithm. J Eur Acad Dermatol Venereol. 2009;23(7):760–772.

[4] Passeron T. Melasma pathogenesis and influencing factors — an overview of the latest research. J Eur Acad Dermatol Venereol. 2013;27(Suppl 1):5–16.

[5] D’Mello SAN, Finlay GJ, Baguley BC, Askarian-Amiri ME. Signaling pathways in melanogenesis. Int J Mol Sci. 2016;17(7):1144. https://doi.org/10.3390/ijms17071144

[6] Bandyopadhyay D. Topical treatment of melasma. Indian J Dermatol. 2009;54(4):303–309.

[7] Gupta AK, Gover MD, Nouri K, Taylor S. The treatment of melasma: a review of clinical trials. J Am Acad Dermatol. 2006;55(6):1048–1065.

[8] Pillaiyar T, Manickam M, Jung SH. Inhibitors of melanogenesis: a review. J Med Chem. 2017;61(17):7395–7418.

[9] Elias PM. Stratum corneum defensive functions: an integrated view. J Invest Dermatol. 2005;125(2):183–200.

[10] Pardeike J, Hommoss A, Müller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm. 2009;366(1–2):170–184.

[11] Hoare TR, Kohane DS. Hydrogels in drug delivery: progress and challenges. Polymer. 2008;49(8):1993–2007.

[12] Souto EB, Müller RH. Lipid nanoparticles: effect on skin penetration and drug release. J Control Release. 2007;123(3):175–182.

[13] Bhattacharjee S. DLS and zeta potential analysis of nanoparticles. J Nanopart Res. 2016;18:1–15.

[14] Na JI, Choi SY, Yang SH, Choi HR, Kang HY, Park KC. Effect of tranexamic acid on melasma: a clinical trial. J Cosmet Dermatol. 2013;12(2):132–137.

[15] Hakozaki T, Minwalla L, Zhuang J, et al. The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br J Dermatol. 2002;147(1):20–31.

[16] Nussbaum S, Benedetto AV. Cosmetic aspects of azelaic acid. Dermatol Surg. 2006;32(6):809–816.

[17] Rendon MI, Gaviria JI. Review of skin-lightening agents. Dermatol Surg. 2005;31(7):886–889.

[18] Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev. 2002;54(Suppl 1):S131–S155.

[19] Gupta M, Vyas A, Jain A. Nanoemulgel-based topical delivery systems: recent advances and applications. J Drug Deliv Sci Technol. 2021;63:102500.

[20] Sharma S, Verma A, Kumar P. FTIR analysis for drug-excipient compatibility studies. Spectrochim Acta A Mol Biomol Spectrosc. 2020;228:117741.

[21] Zhang Y, Xia Q, Li Y, et al. Recent advances in topical drug delivery systems for skin diseases. Int J Pharm. 2017;529(1–2):1–15.

[22] Benson HAE, Watkinson AC. Transdermal and Topical Drug Delivery: Principles and Practice. Hoboken: Wiley; 2012.

[23] Franz TJ. Percutaneous absorption: on the relevance of in vitro data. J Invest Dermatol. 1975;64(3):190–195.

[24] Dragicevic N, Maibach HI. Percutaneous Penetration Enhancers Drug Penetration Into/Through the Skin. Springer; 2017.

[25] Rodrigues M, Pandya AG, Kundu RV. Melasma: current concepts and management. J Drugs Dermatol. 2019;18(11):1073–1079.

[26] Schäfer-Korting M, Mehnert W, Korting HC. Lipid nanoparticles for improved topical drug delivery. Adv Drug Deliv Rev. 2007;59(6):427–443.

[27] Costin GE, Hearing VJ. Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J. 2007;21(4):976–994.

[28] Boo YC. Human skin lightening efficacy of resveratrol and its analogs. Int J Mol Sci. 2020;21(16):5679.

[29] Souto EB, Fangueiro JF, Fernandes AR, et al. Nanomaterials in topical drug delivery systems. Materials. 2020;13(6):1454.

[30] Ogbechie-Godec OA, Elbuluk N. Melasma: an up-to-date comprehensive review. Dermatol Online J. 2017;23(9).

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