Surface-Modified Multifunctional Thymol-Loaded Biodegradable Nanoparticles for Topical Acne Treatment.

Camila Folle,María Luisa García,Marta Espina,Ana Cristina Calpena,Laura Baldomà,Natalia Díaz-Garrido,Ana Maria Marqués,Josefa Badia,Elena Sánchez-López

doi:10.3390/pharmaceutics13091501

Abstract

The present work is focused on the development of novel surface-functionalized poly(lactic-co-glycolic acid) nanoparticles loaded with thymol (TH-NPs) for topical administration enhancing thymol anti-inflammatory, antioxidant and wound healing activities against acne. TH-NPs were prepared by solvent evaporation method using different surface functionalization strategies and obtaining suitable physicochemical parameters and a good short-term stability at 4 °C. Moreover, TH-NPs skin penetration and antioxidant activity were assessed in ex vivo pig skin models. Skin penetration of TH-NPs followed the follicular route, independently of the surface charge and they were able to enhance antioxidant capacity. Furthermore, antimicrobial activity against Cutibacterium acnes was evaluated in vitro by the suspension test showing improved antibacterial performance. Using human keratinocyte cells (HaCat), cytotoxicity, cellular uptake, antioxidant, anti-inflammatory and wound healing activities were studied. TH-NPs were non-toxic and efficiently internalized inside the cells. In addition, TH-NPs displayed significant anti-inflammatory, antioxidant and wound healing activities, which were highly influenced by TH-NPs surface modifications. Moreover, a synergic activity between TH-NPs and their surface functionalization was demonstrated. To conclude, surface-modified TH-NPs had proven to be suitable to be used as anti-inflammatory, antioxidant and wound healing agents, constituting a promising therapy for treating acne infection and associated inflammation.

Highlights

Acne vulgaris is one of the most prevalent skin inflammatory disorders affecting 9.4%of the population worldwide [1,2]
Their pathophysiology is complex, with both internal and external triggers [3]. This disease is induced by several factors such as irregular keratinocyte proliferation and differentiation, increased sebum production by active sebaceous glands and imbalances in the skin microbiota. This imbalance is related to certain Cutibacterium strains, among them Cutibacterium acnes, a normal skin commensal previously known as Propionibacterium acnes [4]
In order to prepare the NPs, the organic phase composed by poly(lactic-co-glycolic acid) (PLGA) and 2.5 mg/mL of TH was dissolved in acetone and the aqueous phase consisted on either phosphatidylcholine (TH-NP-L-) or Poloxamer 188 (TH-NP-P-) or Poloxamer 407 (TH-NP-PP-), for negatively charged particles

Summary

Introduction

Acne vulgaris is one of the most prevalent skin inflammatory disorders affecting 9.4%of the population worldwide [1,2]. Their pathophysiology is complex, with both internal and external triggers [3] This disease is induced by several factors such as irregular keratinocyte proliferation and differentiation, increased sebum production by active sebaceous glands and imbalances in the skin microbiota. Exogenous factors such as hormones, drugs, nutrition, stress or smoke habits, can trigger acne development [5,6]. This combination of factors leads to skin lesions such as whiteheads, blackheads, pustules and cysts developing into swelling and inflammation [7]

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Results

Conclusion