Gel-Dispersed Nanostructured Lipid Carriers Loading Thymol Designed for Dermal Pathologies

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2024 Feb 13

PMID 38348173

Authors

Camila Folle

Ana M Marques

Natalia Diaz-Garrido

Paulina Carvajal-Vidal

Elena Sanchez Lopez

Joaquim Suner-Carbo

Lyda Halbaut

Mireia Mallandrich

Marta Espina

Josefa Badia

Laura Baldoma

Maria Luisa Garcia

Ana Cristina Calpena

Affiliations

Soon will be listed here.

Abstract

Purpose: is one of the most prevalent dermal disorders affecting skin health and appearance. To date, there is no effective cure for this pathology, and the majority of marketed formulations eliminate both healthy and pathological microbiota. Therefore, hereby we propose the encapsulation of an antimicrobial natural compound (thymol) loaded into lipid nanostructured systems to be topically used against acne.

Methods: To address this issue, nanostructured lipid carriers (NLC) capable of encapsulating thymol, a natural compound used for the treatment of acne vulgaris, were developed either using ultrasonication probe or high-pressure homogenization and optimized using 2-star factorial design by analyzing the effect of NLC composition on their physicochemical parameters. These NLC were optimized using a design of experiments approach and were characterized using different physicochemical techniques. Moreover, short-term stability and cell viability using HaCat cells were assessed. Antimicrobial efficacy of the developed NLC was assessed in vitro and ex vivo.

Results: NLC encapsulating thymol were developed and optimized and demonstrated a prolonged thymol release. The formulation was dispersed in gels and a screening of several gels was carried out by studying their rheological properties and their skin retention abilities. From them, carbomer demonstrated the capacity to be highly retained in skin tissues, specifically in the epidermis and dermis layers. Moreover, antimicrobial assays against healthy and pathological skin pathogens demonstrated the therapeutic efficacy of thymol-loaded NLC gelling systems since NLC are more efficient in slowly reducing viability, but they possess lower antimicrobial activity against , compared to free thymol.

Conclusion: Thymol was successfully loaded into NLC and dispersed in gelling systems, demonstrating that it is a suitable candidate for topical administration against acne vulgaris by eradicating pathogenic bacteria while preserving the healthy skin microbiome.

Citing Articles

SLNs and NLCs for Skin Applications: Enhancing the Bioavailability of Natural Bioactives.

Safta D, Bogdan C, Moldovan M Pharmaceutics. 2024; 16(10).

PMID: 39458602 PMC: 11510141. DOI: 10.3390/pharmaceutics16101270.

References

Sachdeva M, Tan J, Lim J, Kim M, Nadeem I, Bismil R . The prevalence, risk factors, and psychosocial impacts of acne vulgaris in medical students: a literature review. Int J Dermatol. 2020; 60(7):792-798. DOI: 10.1111/ijd.15280. View

Lopez-Machado A, Diaz N, Cano A, Espina M, Badia J, Baldoma L . Development of topical eye-drops of lactoferrin-loaded biodegradable nanoparticles for the treatment of anterior segment inflammatory processes. Int J Pharm. 2021; 609:121188. DOI: 10.1016/j.ijpharm.2021.121188. View

Alvarado H, Abrego G, Souto E, Garduno-Ramirez M, Clares B, Garcia M . Nanoemulsions for dermal controlled release of oleanolic and ursolic acids: In vitro, ex vivo and in vivo characterization. Colloids Surf B Biointerfaces. 2015; 130:40-7. DOI: 10.1016/j.colsurfb.2015.03.062. View

Briganti S, Picardo M . Antioxidant activity, lipid peroxidation and skin diseases. What's new. J Eur Acad Dermatol Venereol. 2004; 17(6):663-9. DOI: 10.1046/j.1468-3083.2003.00751.x. View

Gonzalez-Pizarro R, Silva-Abreu M, Calpena A, Egea M, Espina M, Garcia M . Development of fluorometholone-loaded PLGA nanoparticles for treatment of inflammatory disorders of anterior and posterior segments of the eye. Int J Pharm. 2018; 547(1-2):338-346. DOI: 10.1016/j.ijpharm.2018.05.050. View

Messager S, Hann A, Goddard P, Dettmar P, Maillard J . Use of the 'ex vivo' test to study long-term bacterial survival on human skin and their sensitivity to antisepsis. J Appl Microbiol. 2004; 97(6):1149-60. DOI: 10.1111/j.1365-2672.2004.02403.x. View

Sarango-Granda P, Espinoza L, Diaz-Garrido N, Alvarado H, Rodriguez-Lagunas M, Baldoma L . Effect of Penetration Enhancers and Safety on the Transdermal Delivery of Apremilast in Skin. Pharmaceutics. 2022; 14(5). PMC: 9147106. DOI: 10.3390/pharmaceutics14051011. View

Maupas C, Moulari B, Beduneau A, Lamprecht A, Pellequer Y . Surfactant dependent toxicity of lipid nanocapsules in HaCaT cells. Int J Pharm. 2011; 411(1-2):136-41. DOI: 10.1016/j.ijpharm.2011.03.056. View

Andersen A . Final report on the safety assessment of sodium p-chloro-m-cresol, p-chloro-m-cresol, chlorothymol, mixed cresols, m-cresol, o-cresol, p-cresol, isopropyl cresols, thymol, o-cymen-5-ol, and carvacrol. Int J Toxicol. 2006; 25 Suppl 1:29-127. DOI: 10.1080/10915810600716653. View

10.

Abrego G, Alvarado H, Souto E, Guevara B, Halbaut Bellowa L, Parra A . Biopharmaceutical profile of pranoprofen-loaded PLGA nanoparticles containing hydrogels for ocular administration. Eur J Pharm Biopharm. 2015; 95(Pt B):261-70. DOI: 10.1016/j.ejpb.2015.01.026. View

11.

Alvarez-Roman R, Naik A, Kalia Y, Guy R, Fessi H . Skin penetration and distribution of polymeric nanoparticles. J Control Release. 2004; 99(1):53-62. DOI: 10.1016/j.jconrel.2004.06.015. View

12.

Slavkova M, Tzankov B, Popova T, Voycheva C . Gel Formulations for Topical Treatment of Skin Cancer: A Review. Gels. 2023; 9(5). PMC: 10216957. DOI: 10.3390/gels9050352. View

13.

Sosa L, Calpena A, Silva-Abreu M, Espinoza L, Rincon M, Bozal N . Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis. Pharmaceutics. 2019; 11(7). PMC: 6680481. DOI: 10.3390/pharmaceutics11070312. View

14.

Amasya G, Inal O, Tuba Sengel-Turk C . SLN enriched hydrogels for dermal application: Full factorial design study to estimate the relationship between composition and mechanical properties. Chem Phys Lipids. 2020; 228:104889. DOI: 10.1016/j.chemphyslip.2020.104889. View

15.

MacGowan A, Wootton M, Hedges A, Bowker K, HOLT H, Reeves D . A new time-kill method of assessing the relative efficacy of antimicrobial agents alone and in combination developed using a representative beta-lactam, aminoglycoside and fluoroquinolone. J Antimicrob Chemother. 1996; 38(2):193-203. DOI: 10.1093/jac/38.2.193. View

16.

Rincon M, Calpena A, Fabrega M, Garduno-Ramirez M, Espina M, Rodriguez-Lagunas M . Development of Pranoprofen Loaded Nanostructured Lipid Carriers to Improve Its Release and Therapeutic Efficacy in Skin Inflammatory Disorders. Nanomaterials (Basel). 2018; 8(12). PMC: 6316124. DOI: 10.3390/nano8121022. View

17.

Carvajal-Vidal P, Gonzalez-Pizarro R, Araya C, Espina M, Halbaut L, Gomez de Aranda I . Nanostructured lipid carriers loaded with Halobetasol propionate for topical treatment of inflammation: Development, characterization, biopharmaceutical behavior and therapeutic efficacy of gel dosage forms. Int J Pharm. 2020; 585:119480. DOI: 10.1016/j.ijpharm.2020.119480. View

18.

Ariffin N, Hasham R . Assessment of non-invasive techniques and herbal-based products on dermatological physiology and intercellular lipid properties. Heliyon. 2020; 6(5):e03955. PMC: 7251381. DOI: 10.1016/j.heliyon.2020.e03955. View

19.

Sahoo C, Paidesetty S, Padhy R . The recent development of thymol derivative as a promising pharmacological scaffold. Drug Dev Res. 2021; 82(8):1079-1095. DOI: 10.1002/ddr.21848. View

20.

Tayel K, Attia M, Agamia N, Fadl N . Acne vulgaris: prevalence, severity, and impact on quality of life and self-esteem among Egyptian adolescents. J Egypt Public Health Assoc. 2020; 95(1):30. PMC: 7642029. DOI: 10.1186/s42506-020-00056-9. View