Abstract
Photoaging, the premature aging of skin induced by ultraviolet rays, is characterized by wrinkling, roughness, laxity, and pigmentary changes. Various natural and synthetic retinoids have been explored for the treatment of aging. Among retinoids, adapalene (Ada, 0.3%) is one of the most potent and widely used drugs to treat photoaging. However, it causes irritant reactions that limit its acceptance by patients. Several studies have shown the applicability of Lysozyme (Lys)-shelled microbubbles (MBs) for drug delivery through sonophoresis, and recently we have shown its efficiency to treat inflammatory skin disease. Here, we report the construction of novel Ada-LysMBs based on opposite electric charges for combined effects to treat photoaging. The Ada-LysMBs were self-assembled and had a mean diameter of 2857 nm. The maximum loading efficiency of Ada onto LysMBs was 13.99 ± 0.59%. An acoustic power density of 3 W/cm2 for 1 min revealing maximum penetration depth of LysMBs was optimized for further in vitro and in vivo studies of Ada-LysMBs. It was observed that in vitro Ada release from Ada-LysMBs at 6 h after ultrasound (US) treatment was more rapid at pH 7.4 (82%) than at pH 5.5 (73%). Franz diffusion experiments on isolated porcine skin indicated that US approximately doubled Ada delivery by Ada-LysMBs and Ada + LysMBs at 12 h and six-fold Lys permeation by LysMBs at 6 h, compared to these treatments alone. A 5-week in vivo study in mice identified significant wrinkle reduction in animals treated with US plus Ada-LysMBs. Our findings indicate that US may be used with Ada-LysMBs in the water phase to treat photoaging by normalizing hyperkeratinization and promoting collagen synthesis.
Highlights
Ultraviolet (UV) irradiation from the sun has deleterious effects on the human skin and causes sunburn, immune suppression, cancer, and photoaging [1]
Ultrasound-mediated microbubbles in skin photoaging potential of the LysMBs and Ada-LysMBs, dispersed in an aqueous solution, was measured using a Nanoparticle Analyzer (Horiba)
These findings indicated that ultrasound energy enhanced the drug release by 40.1–260.9%, and demonstrated that the efficiency of Ada release from Ada-LysMBs was affected by the pH of the release medium
Summary
Ultraviolet (UV) irradiation from the sun has deleterious effects on the human skin and causes sunburn, immune suppression, cancer, and photoaging [1]. Photoaged skin is characterized by fine and coarse wrinkling, roughness, dryness, laxity, telangiectasia, and solar comedones [3,4,5]. It is typified by impaired barrier function [6], variable epidermal thickness, dermal elastosis, decreased and fragmented collagen, increased matrixdegrading metalloproteinases, inflammatory infiltrates, and vessel dilation [7]. Such changes have negative effects on the quality of life, with deleterious impact on well-being, physical attractiveness, and self-confidence [8]. Photoaging represents a common complaint of both cosmetic and medical patients, and it is imperative for clinicians to evaluate new therapeutic approaches
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