Elastin Production Research Articles

IMMEDIATE LIFTING EFFECT AFTER MICROFOCUSED ULTRASOUND APPLICATION

High-Intensity Focused Ultrasound (HIFU) treatment is an innovative technique for non-invasive facial aesthetic treatments. This work aims to present the theoretical foundations, mechanism of action, and effectiveness of this technology in facial rejuvenation through a case report. HIFU is a technique based on the emission of focused ultrasonic waves, which act directly on the layers of the skin, stimulating the natural process of collagen and elastin production known as neocollagenesis and neoelastogenesis. By precisely directing ultrasonic energy, it generates heat above 55°C at the focal point, leading to points of thermal coagulation (TCPs) in the target tissue and promoting tissue contraction, resulting in a non-surgical and long-lasting lifting effect. Several scientific studies demonstrating the efficacy of high-intensity focused ultrasound in treating expression lines, skin sagging, wrinkles, and improving facial contour have been reviewed. Furthermore, the technology has been successfully applied in specific areas, such as the periocular region, for treating periorbital wrinkles. The findings indicate that HIFU is safe and well-tolerated by patients, with minimal side effects and associated risks. The absence of recovery time and the possibility of immediate return to daily activities have contributed to the growing popularity of the procedure. In conclusion, high-intensity focused ultrasound emerges as a promising and effective alternative in the field of orofacial harmonization, providing consistent results and patient satisfaction.

Use of retinoids in the treatment of skin lesions and prevention of signs of skin aging - a systematic review

Retinoids are a group of substances that include vitamin A and its natural and synthetic derivatives. They are used in the treatment of various skin diseases, such as: rosacea, acne vulgaris, psoriasis. In addition, recently there is a lot of information about the action of preventing photoaging. Oral retinoids have been proven to be the most effective treatment for acne of various severity available today. Through their comprehensive action, affecting the four main factors associated with the pathogenesis of acne, they significantly reduce skin changes. Externally applied retinoids regulate the renewal of epidermal cells, stimulate the production of collagen fibers, increase the production of elastin, and lead to an increase in the number and activity of fibroblasts. Therefore, more and more people are using preparations containing retinoids to prevent skin aging. It has been proven that this procedure leads to shallower wrinkles and slows down the appearance of new ones, and evens out the skin tone. Retinoids are effective substances, but their use is associated with the risk of various side effects, the most common of which are: skin irritation, photosensitisation, headaches, muscle and joint pain, and teratogenicity.

Study of Elastin, Hydrolyzed Collagen and Collagen-like Products in a Tri-Layered Chitosan Membrane to Test Anti-Aging Skin Properties.

The use of animal testing in the cosmetic industry is already prohibited in more than 40 countries, including those of the EU. The pressure for it to be banned worldwide in the future is increasing, so the need for animal alternatives is of great interest today. In addition, using animals and humans in scientific research is ethically reprehensible. This study aimed to prove some of the anti-aging properties of elastin (EL), hydrolyzed collagen (HC), and two vegan collagen-like products (Veg Col) in a tri-layered chitosan membrane that was ionically crosslinked with sodium tripolyphosphate (TPP). In the first approach, as a way of representing different layers of a biological system, such as the epidermis and the two dermis sublayers, EL, HC, or Veg Col were independently introduced into the two inner layers (2L(i+b)). Their effects were compared with those of their introduction into three layers (3L). Different experiments were performed on the membrane to test its elasticity, hydration, moisture retention, and pore reduction at different concentrations of EL, HC, and Veg Col, and the results were normalized vs. a blank membrane. This new alternative to animal or human testing can be suitable for proving certain efficacy claims for active ingredients or products in the pharmaceutical, nutritional, and cosmetic fields.

Evaluation of the Antitumor Potential of Soloxolone Tryptamide against Glioblastoma Multiforme Using in silico, in vitro, and in vivo Approaches

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by uncontrollable diffusive growth, resistance to chemo- and radiotherapy, and a high recurrence rate leading to a low survival rate of patients with GBM. Due to a large number of signaling pathways regulating GBM pathogenesis, one of the promising directions is development of novel anti-glioblastoma compounds based on natural metabolites capable of affecting multiple targets. Here, we investigated the antitumor potential of the semisynthetic triterpenoid soloxolone tryptamide (STA) against human glioblastoma U87 cells. STA efficiently blocked the growth of U87 cells in 2D and 3D cultures, enhanced adhesiveness of tumor cells, and displayed synergistic cytotoxicity with temozolomide. In silico analysis suggested that the anti-glioblastoma activity of STA can be explained by its direct interaction with EGFR, ERBB2, and AKT1 which play an important role in the regulation of GBM malignancy. Along with direct effect on U87 cells, STA normalized tumor microenvironment in murine heterotopic U87 xenograft model by suppressing the development of immature blood vessels and elastin production in the tumor tissue. Taken together, our results clearly demonstrate that STA can be a novel promising antitumor candidate for GMB treatment.

Transcriptome Analysis of Human Vascular Smooth Muscle Cells Cultured on a Polyglycolic Acid Mesh Scaffold

To construct tissue-engineered blood vessels (TEBVs) in vitro, it is necessary to transfer seed cells to three-dimensional (3D) scaffolds for culture. However, what happens to the behavior of the cells after they are transferred to the scaffold is unclear. Therefore, in this study, a transcriptome analysis was used to characterize the differentially expressed genes (DEGs) of vascular smooth muscle cells (VSMCs) before and after transfer to 3D polyglycolic acid (PGA) scaffolds and to understand the changes in functional gene expression in the early stage of 3D culture. Transcriptome sequencing results showed that DEGs in the seed cells were mainly enriched in cell proliferation and cell-cell adhesion. The DEGs of cells grown in a 3D PGA scaffold (PGA-VSMCs) were mainly enriched in signal transduction. Furthermore, we found that ERK1/2 was significantly activated in PGA-VSMCs and inhibiting the phosphorylation level of ERK 1/2 in PGA-VSMCs significantly increased the expression of elastin. In conclusion, the PGA scaffold material altered gene expression in VSMCs and affected the elastin production. This study advances our understanding of biomaterial-cell interactions and provides valuable insights for improving the cultivation of TEBVs.

Skin boosters – The upcoming boom in cosmetic dermatology for healthy skin

Skin-booster injections are popular esthetic treatments that are highly sought after because they are minimally invasive. They are used as one of the skin rejuvenation therapies to restore healthy hydrating skin of not only the face but also the neck, hands, and other regions of the body. Skin boosting is a revolutionary method of delivering either hyaluronic acid (HA) infused with other vitamins, amino acids, and antioxidants or HA per se to stimulate the body’s natural response that is to make more collagen and elastin. Extrinsic and intrinsic factors affect the quality and vitality of our skin resulting in dull and not-so-esthetically appealing skin. Skin boosters are injected in the papillary dermis where they activate the fibroblast cells, which in turn promotes new collagen and elastin formation and reduces the activity of collagenase resulting in smooth glowing skin. There are multiple different techniques of injecting depending on the injector after clinical assessment of the patient. Skin boosters provide good hydration instant glow, reduce wrinkles and fine lines, and improve the texture of the skin. Skin boosters are different from fillers. Filler’s act as a tool for sculpting by filling up the volume deficiencies, whereas skin boosters do not exert any mechanical effects, they only stimulate further collagen and elastin production through their biochemical properties. In comparison with various skin rejuvenation procedures and topical medications, the cost of skin boosters is higher; however, various factors determine the final price. Cost constraint is one of the major limiting factors for wide usage of skin booster. Amidst our multiple skincare routines, there is a growing need to seek new methods of maintaining healthy skin. The ultimate effects of skin boosters are skin hydration, rejuvenation, and healthy-looking young and vibrant skin.

Effect of Marine-Derived Saccharides on Human Skin Fibroblasts and Dermal Papilla Cells.

The skin is the largest organ of the human body, composed of a diverse range of cell types, non-cellular components, and an extracellular matrix. With aging, molecules that are part of the extracellular matrix undergo qualitative and quantitative changes and the effects, such as a loss of skin firmness or wrinkles, can be visible. The changes caused by the aging process do not only affect the surface of the skin, but also extend to skin appendages such as hair follicles. In the present study, the ability of marine-derived saccharides, L-fucose and chondroitin sulphate disaccharide, to support skin and hair health and minimize the effects of intrinsic and extrinsic aging was investigated. The potential of the tested samples to prevent adverse changes in the skin and hair through stimulation of natural processes, cellular proliferation, and production of extracellular matrix components collagen, elastin, or glycosaminoglycans was investigated. The tested compounds, L-fucose and chondroitin sulphate disaccharide, supported skin and hair health, especially in terms of anti-aging effects. The obtained results indicate that both ingredients support and promote the proliferation of dermal fibroblasts and dermal papilla cells, provide cells with a supply of sulphated disaccharide GAG building blocks, increase ECM molecule production (collagen and elastin) by HDFa, and support the growth phase of the hair cycle (anagen).

Investigation on the Biological Safety and Activity of a Gluconolactone-Based Lotion for Dermocosmetic Application.

(1) Background: Cosmeceuticals are formulas enriched with active ingredients that exert efficacy on different skin molecular targets. (2) Methods: Cell viability and the absence of potential irritant risk were evaluated on keratinocytes (HaCaT), fibroblasts (NHDF), adipocytes (3T3-L1), sebocytes (PCi-SEB_CAU) and reconstructed human epidermis (RHE), respectively. Several treatments were performed to evaluate the ability of the lotion to stimulate the production of collagen and elastin, stimulate the differentiation of keratinocytes and reduce the number of senescent cells following UVB stimulation. In addition, the modulation of genes involved in the production, storage and accumulation of sebum were investigated. (3) Results: The results obtained demonstrated the biosafety of the formula in all cell lines tested. The 24-h treatment with non-cytotoxic concentrations determined an increase in the expression of the collagen (COL1A1), elastin (ELN) and involucrin (IVL) genes, while a reduction of peroxisome proliferator-activated receptor-gamma (PPARγ) gene expression and a reduction of SA-βgal-positive cells were found. Moreover, the treatment did not interfere with normal steroid 5-alpha reductase (5RDA3) gene expression levels. (4) Conclusions: Data collected demonstrated the biosafety of the lotion, the non-comedogenic property and a multi targets anti-aging effect. In particular, data collected on the booster lotion make it a valid way to counteract the pore dilatation aging related.

Introducing aesthetic regenerative scaffolds: An immunological perspective.

Skin aging arises from immunological responses to tissue deterioration and damage. Tissue repair processes encompass the regeneration of original tissue and 'scarless' wound healing seen in foetuses, and the extreme fibrotic responses and scarring seen in adults. Anti-aging aesthetic medicine uses interventions like biomaterial-based fillers to influence these immunological responses and renew aged tissue structure and function. At filler injection sites, an inflammatory response occurs that causes a spectrum of outcomes, ranging from tissue regeneration to fibrosis and filler encapsulation. Importantly, the resulting inflammatory pathway can be predetermined by the biomaterial injected. By understanding this immunological process, we can develop Aesthetic Regenerative Scaffolds (ARS) - aesthetic injectable biomaterials - to direct inflammatory wound healing away from chronic, fibrotic responses, and towards physiological tissue regeneration. We identified and reviewed literature on the immunological and cellular responses to injected dermal fillers, whereby the wound healing response to the injection was moderated under the influence of an injected biomaterial. We described the mechanisms of dermal wound healing and the use of ARS to direct healing towards tissue regeneration instead of scarring. We also summarised studies on extracellular matrix remodeling by calcium hydroxylapatite. We found that Calcium hydroxylapatite fillers produce collagen as they gradually degrade and their spherical structures serve as a scaffold for tissue regeneration. Furthermore, CaHA improved fibroblast contractility, collagen type III and elastin production, proliferation and angiogenesis with less inflammation than hyaluronic acid fillers. Regneration pathways can be influenced at specific points between a facial filler biomaterial and the wound healingmechanisms at its site of implantaion. Physicians can select scaffolds that direct the immune response away from a fibrotic chronic inflammatory pathway and towards regeneration to enable true repair of the aging skin.

Nanomaterials based on chitosan for skin regeneration: an update.

Nanomaterials based on chitosan for skin regeneration: an update.

Bilateral Congenital Nasolacrimal Duct Obstruction in Williams-Beuren Syndrome.

A 23-year-old patient with Williams-Beuren syndrome presented with ocular irritation and bilateral persistent tearing. Despite probing as an infant which showed bilateral nasolacrimal duct obstruction, dacryocystorhinostomy had been avoided due to the patient's syndromic supravalvular stenosis and related anesthesia risk. As the known diminished production of elastin in Williams-Beuren syndrome causes an array of associated vascular diseases, this case report hypothesizes that the lacrimal duct becomes obstructed through a similar mechanism. This case presents the unique findings of bilateral congenital nasolacrimal duct stenosis in a Williams-Beuren syndrome patient.

Possibilities of microneedling in the combined therapy of vitiligo. Literature review

The Vitiligo therapy is still a topical issue today. According to the Russian and European clinical guidelines, modern therapy for vitiligo includes UVB-311 nm phototherapy, topical glucocorticoids and topical calcineurin inhibitors. Standard treatment regimens require a long time of application and their effectiveness on the average does not exceed 40%, which leads to disappointment in the treatment not only for patients but also for dermatologists. In this regard an active search for therapies for vitiligo continues. Thus, one of the modern options for the treatment of this disease is microneedling.
 Microneedling is a relatively new, easy to perform, safe and minimally invasive therapeutic technique that enhances the regenerative process by creating numerous microtraumas occurring when shallow needles are punctured into the skin. This procedure causes a cascade of reactions similar to the wound healing process, stimulating the production of collagen, elastin and growth factors and increases the migration of melanocytes and keratinocytes leading to repigmentation of vitiligo lesions. Local damage to the skin with needles enhances penetration of active ingredients into deeper layers, so microneedling is often combined with the use of UV light, as well as with various biopharmaceuticals to increase efficiency. Although the procedure is relatively new it has demonstrated efficacy, good tolerability, limited undesirable effects and a short recovery time, making micro-needling a promising treatment for vitiligo.
 This article is a review in nature. The purpose of this review is to update the available information on the treatment of vitiligo as well as to explore a promising new method of therapy. A systematic literature review was conducted using PubMed, Cochrane Library, CyberLeninka, Clinicaltrial.govand the open-access Internet databases to examine the efficacy, principles of action, and tolerability of the new treatment. Key words used in the literature search in the aforementioned databases were vitiligo, vitiligo treatment, microneedling, and quality of life .The results of various clinical studies are presented.
 This review is addressed to practicing dermatovenerologists interested in vitiligo therapy.

Efficacy of Acetyl Hexapeptide-8 Ampoule on Improvement of Elasticity in C3H Mice Skin

Purpose: Acetyl hexapeptide-8 (AH-8) had been reportedly effective in improving keratinocytes. Ampoules containing AH-8 as an active ingredient were prepared, and their efficacy for improving skin elasticity was evaluated.Methods: Ampoules containing 3% and 5% AH-8 were prepared, and their efficacy was evaluated. C3H mice were pretreated with different AH-8 ampoule concentrations and then irradiated with UVB for 6 weeks. Changes in the number of collagen and elastic fibers from paraffin-embedded skin tissues were quantitatively measured using an image analysis program.Results: Our data showed that the skin of C3H mice with UVB-irradiated markedly decreased the collagen levels compared to the control. Moreover, pretreatment of 3% and 5% AH-8 ampoules on UVB irradiation increased collagen production. Furthermore, the elastin production was decreased in the UVB-irradiated group compared to the control and the elastin level in the skin of C3H mice was similar in both pretreated with 5% AH-8 on the UVB irradiation and control groups.Conclusions: This study has proven that HA-8 ampoules had a high capability of improving elasticity when compared to vehicle ampoule-containing ginkgo leaf and green tea extracts. Moreover, this study revealed the efficacy of AH-8 for increasing skin elasticity in terms of a cosmetic active ingredient.

Aortic Stress Activates an Adaptive Program in Thoracic Aortic Smooth Muscle Cells That Maintains Aortic Strength and Protects Against Aneurysm and Dissection in Mice.

When aortic cells are under stress, such as increased hemodynamic pressure, they adapt to the environment by modifying their functions, allowing the aorta to maintain its strength. To understand the regulation of this adaptive response, we examined transcriptomic and epigenomic programs in aortic smooth muscle cells (SMCs) during the adaptive response to AngII (angiotensin II) infusion and determined its importance in protecting against aortic aneurysm and dissection (AAD). We performed single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) analyses in a mouse model of sporadic AAD induced by AngII infusion. We also examined the direct effects of YAP (yes-associated protein) on the SMC adaptive response in vitro. The role of YAP in AAD development was further evaluated in AngII-infused mice with SMC-specific Yap deletion. In wild-type mice, AngII infusion increased medial thickness in the thoracic aorta. Single-cell RNA sequencing analysis revealed an adaptive response in thoracic SMCs characterized by upregulated genes with roles in wound healing, elastin and collagen production, proliferation, migration, cytoskeleton organization, cell-matrix focal adhesion, and PI3K-PKB/Akt (phosphoinositide-3-kinase-protein kinase B/Akt) and TGF-β (transforming growth factor beta) signaling. ScATAC-seq analysis showed increased chromatin accessibility at regulatory regions of adaptive genes and revealed the mechanical sensor YAP/transcriptional enhanced associate domains as a top candidate transcription complex driving the expression of these genes (eg, Lox, Col5a2, Tgfb2). In cultured human aortic SMCs, cyclic stretch activated YAP, which directly bound to adaptive gene regulatory regions (eg, Lox) and increased their transcript abundance. SMC-specific Yap deletion in mice compromised this adaptive response in SMCs, leading to an increased AAD incidence. Aortic stress triggers the systemic epigenetic induction of an adaptive response (eg, wound healing, proliferation, matrix organization) in thoracic aortic SMCs that depends on functional biomechanical signal transduction (eg, YAP signaling). Our study highlights the importance of the adaptive response in maintaining aortic homeostasis and preventing AAD in mice.

NECK TISSUE REJUVENATION WITH PERCUTANEOUS COLLAGEN INDUCTION, DRUG DELIVERY AND HOME CARE

Percutaneous collagen induction or microneedling is a procedure that, through the opening of microchannels on the surface of the skin, generates healing induced by platelets that increase the production of growth factors and cytokines, triggered by a controlled inflammation that stimulates the production of collagen and elastin. With the microneedling protocol and the use of drug delivery in mature skin, the results are optimized by the association of specific actives that will be more effectively absorbed by the microchannels. The objective of this work is to carry out a brief literature review and case report on the use of the percutaneous collagen induction method with the association of drug-delivery and home care in the neck region with the aim of superficial and deep tissue rejuvenation. The results found through clinical observation were a significant improvement in the appearance of aging, dryness, superficial flaccidity, fine rhytids, photoaging and devitalized appearance. Little or no results were observed in the improvement of deep flaccidity, horizontal wrinkles and central vertical bands of the neck after 4 sessions of the protocol.

Improvement in Skin Elasticity Using Red Deer Umbilical Cord Lining Mesenchymal Stem Cell Conditioned Media.

Significant improvement in skin tone was reported after topical application of a facial cream (CALECIM® Professional Multi-Action Cream, CALECIM Cosmeceuticals, Singapore) containing conditioned media (CM) derived from Red Deer Umbilical Cord Lining Mesenchymal Stem Cell (RD-CLMSC) culture. This study investigates the paracrine effects of RD-CLMSC-CM on human dermal fibroblasts (HDF) to understand how it may increase skin turgor and elasticity. Skin aging is associated with lower levels of extracellular matrix components such as hyaluronic acid (HA) and elastin, resulting in poor skin turgor and elasticity. Histochemical staining followed by photocolorimetry demonstrated that RD-CLMSC-CM upregulated HDF expression of elastin by 56% and HA by 83% compared with DMEM/10% Fetal Calf Serum (FCS).To further quantify the effects of CM, a proliferation assay was used to assess HDF response to RD-CLMSC-CM exposure. Exposure to RD-CLMSC-CM resulted in the highest increase in HDF proliferation over DMEM/10% FCS (113%) followed by Human (H)-CLMSC-CM (112%), then Human Foreskin Fibroblast (FSF)-CM (16%).These experimental results demonstrate both the cross-species efficacy and lack of toxicity of RD-CLMSC-CM on HDF. These pre-clinical studies also suggest the clinical effects of RD-CLMSC-CM on skin turgor may be related to increased HA and elastin production by HDF, as well as enhanced proliferation. J Drugs Dermatol. 2023;21(1):82-89. doi:10.36849/JDD.6906.

Low Expression of p53 in Sacrouterine Ligament as A Risk Factor for Stage III-IV Uterine Prolapse

Introduction: As life expectancy increases, so does the incidence of pelvic organ prolapse (POP). Low expression of p53 may lead to reduced production and deposition of elastin in the extracellular matrix thus it may increase the risk for POP. This study aims to determine the relationship between p53 expression and the incidence of grade III-IV POP. Methods: This observational case-control study involved women with grade III-IV POP that underwent a total hysterectomy at Sanglah General Hospital Denpasar as the case group. The control group was non-prolapsed women who were matched to the case for the variables of age, parity, body mass index (BMI), and occupation to minimize bias. The p53 expression was grouped into low (<146.90) and high (≥146.90) expressions according to the optimal cut-off value obtained from the receiver operating characteristic curve. Bivariate analysis between p53 expression and risk of POP was performed using the Chi-square test. Results: A total of 44 patients were included in this study with 22 patients with grade III-IV POP and 22 patients without POP. There were no significant differences in age, parity, BMI, and occupation between the two groups. Low p53 expression increased the risk of stage III-IV uterine prolapse by 20.25 times higher (OR = 20.25; 95% CI = 4.375-93.722; p = 0.000). Conclusion: The low p53 expression in the sacrouterine ligament is a significant risk factor for grade III and IV POP.

Polyisocyanides as a substrate to trigger vaginal fibroblast functioning in an in vitro model for prolapse repair.

Pelvic organ prolapse (POP) is the descent of the bladder, uterus, and/or rectum into the vagina. POP is associated with altered vaginal fibroblast functionality and connective tissue composition in the vaginal wall. The results of surgical intervention are poor, which may be related to the lack of true restoration of the connective tissue. An innovative treatment addresses tissue repair after surgery by the introduction of a bioactive supplement that enhances the healing process through collagen and elastin deposition. As a novel strategy, we first studied the effects in an in vitro model. Here, we investigate how the presence of cell binding GRGDS (RGD) peptides on the highly biomimetic polyisocyanide (PIC) gel facilitates and promotes the function of primary vaginal fibroblasts isolated from a POP patient. Fibroblast function was analyzed in terms of morphology, proliferation, and extracellular matrix (ECM) deposition and remodeling. RGD modification of the gel facilitated cell spread and proliferation. Quantitative outcomes of the ECM content indicated increased production of collagen and elastin by fibroblasts on gels with the highest RGD density. The in vitro results suggest that PIC-RGD hydrogel application may translate into improved connective tissue healing in the pelvic floor, which is essential for its use as a regeneration promoting additive in surgery.

Enhanced anti-wrinkle activity of adlay bran fermented with Lactobacillus brevis MJM60390.

The aim of this study was to screen the lactic acid bacteria for fermentation of adlay bran and evaluate the anti-wrinkle effect of fermented and non-fermented adlay bran. Adlay bran was fermented with candidate LAB and extracted with 70% ethanol. The extracts from LAB-fermented adlay bran and non-fermented adlay bran were evaluated for the anti-wrinkle effects by measuring the hyaluronan, collagen, and elastin production in cells using ELISA kit. The molecular anti-wrinkle mechanism was investigated by RT-qPCR. Furthermore, the antioxidant activity, total phenolic and flavonoid content were also determined. Among the tested LAB, Lactobacillus brevis MJM60390 was selected for the highest glycosidase activity. Both extracts from adlay bran (NFAB) and L. brevis MJM60390-fermented adlay bran (LBFAB) showed anti-wrinkle effect, and LBFAB showed higher activity. Compared with control, hyaluronan production was increased by 24.73% and 59.38%, collagen production was increased by -13.08% and 34.19%, and the elastin production was increased by 29.78% and 53.73% by NFAB and LBFAB treatment, respectively. Investigation on the mRNA expression showed that LBFAB upregulated the expression of Has 2 and Has 3 and downregulate HYAL1 and HYAL2. LBFAB also upregulated the mRNA expression of COL1A1, COL1A2, ELN and inhibited the expression of collagenase and elastase. However, not all of these genes were regulated by NFAB. Furthermore, the antioxidant activity was significantly increased after fermentation, and the content of the phenolic and flavonoid compounds also increased in the LBFAB. In this study, we demonstrated that fermentation of adlay bran with L. brevis MJM60390 enhanced the anti-wrinkle activity through increasing the hyaluronan synthesis in keratinocytes and improving collagen and elastin production in dermal fibroblasts.

Laser-assisted nanoparticle delivery to promote skin absorption and penetration depth of retinoic acid with the aim for treating photoaging

Retinoic acid (RA) is an approved treatment for skin photoaging induced by ultraviolet (UVA). Topically applied RA is mainly located in the stratum corneum (SC) with limited diffusion into the deeper strata. A delivery system capable of facilitating dermal delivery and cellular internalization for RA is critical for a successful photoaging therapy. Two delivery approaches, namely nanoparticles and laser ablation, were combined to improve RA’s absorption efficacy and safety. The nanoparticle absorption enhancement by the lasers was compared between full-ablative (Er:YAG) and fractional (CO2) modalities. We fabricated poly-L-lactic acid (PLA) and PLA/poly(lactic-co-glycolic acid) (PLGA) nanoparticles by an emulsion-solvent evaporation technique. The mean size of PLA and PLA/PLGA nanocarriers was 237 and 222 nm, respectively. The RA encapsulation percentage in both nanosystems was > 96 %. PLA and PLA/PLGA nanocarriers promoted RA skin deposition by 5- and 3-fold compared to free control. The ablative lasers further enhanced the skin deposition of RA-loaded nanoparticles, with the full-ablative laser showing greater permeation enhancement than the fractional mode. The skin biodistribution assay evaluated by confocal and fluorescence microscopies demonstrated that the laser-assisted nanoparticle delivery achieved a significant dermis and follicular accumulation. The cell-based study indicated a facile uptake of the nanoparticles into the human dermal fibroblasts. The nanoparticulate RA increased type I collagen and elastin production in the UVA-treated fibroblasts. A reduction of matrix metalloproteinase (MMP)-1 was also highlighted in the photoaging cells. The calculation of therapeutic index (TI) by multiplying collagen/elastin elevation percentage and skin deposition predicted better anti-photoaging performance in Er:YAG laser-assisted nanoparticle delivery than CO2 laser. Nanoencapsulation of RA decreased the cytotoxicity against skin fibroblasts. In vivo skin tolerance test on a nude mouse showed less skin damage after topical application of the nanoparticles than free RA. Our results hypothesized that the laser-mediated nanoparticle delivery provided an efficient and safe use for treating photoaging.