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Dermatology and Therapy May 2024A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially...
INTRODUCTION
A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data.
METHODS
In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated.
RESULTS
At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P < 0.001). CAB resulted in > 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P < 0.001, both). Most TEAEs were of mild-moderate severity, and < 3% of CAB-treated participants discontinued study/treatment because of AEs. Transient increases from baseline in scaling, erythema, itching, burning, and stinging were observed with CAB, but resolved back to or near baseline values by week 12.
CONCLUSIONS
The innovative fixed-dose, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel was efficacious and well tolerated in children, adolescents, and adults with moderate-to-severe acne. Half of participants achieved clear/almost clear skin by 12 weeks, rates not previously seen in clinical studies of other topical acne products.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT04214639 and NCT04214652.
PubMed: 38724841
DOI: 10.1007/s13555-024-01155-7 -
PloS One 2020Photoaging, the premature aging of skin induced by ultraviolet rays, is characterized by wrinkling, roughness, laxity, and pigmentary changes. Various natural and...
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.
Topics: Adapalene; Animals; Dermatologic Agents; Drug Delivery Systems; Female; Mice; Mice, Inbred BALB C; Microbubbles; Muramidase; Retinoids; Skin Aging; Swine; Ultrasonic Waves; Ultraviolet Rays
PubMed: 32438389
DOI: 10.1371/journal.pone.0232617 -
Pharmaceutics Jun 2024Biodegradable aliphatic polyester formulations as carriers for topical drug delivery show the potential to encapsulate structurally different therapeutic compounds....
Biodegradable aliphatic polyester formulations as carriers for topical drug delivery show the potential to encapsulate structurally different therapeutic compounds. Poly(octamethylene suberate) (POS) nanoparticles (POS-NPs) were used as a matrix to encapsulate four therapeutic molecules used to treat skin disorders: caffeine (CF), quercetin (QR), hydrocortisone (HC), and adapalene (AD). Hydrophobicity and chemical structure of bioactive compounds (BCs) influenced the physicochemical stability of drug-loaded nanoparticles. The particle size of drug-loaded nanoparticles was between 254.9 nm for the CF-POS-NP and 1291.3 for QR-POS-NP. Particles had a negative charge from -27.6 mV (QR) to -49.2 mV (HC). Drug loading content for all BC-POS-NPs varies between 36.11 ± 1.48% (CF-POS-NP) and 66.66 ± 4.87% (AD-POS-NP), and their entrapment efficiency is relatively high (28.30 ± 1.81% and 99.95 ± 0.04%, respectively). Calorimetric analysis showed the appearance of polymorphism for AD- and HC-loaded systems and the drug's complete solubilisation into all nanoparticle formulations. FTIR and NMR spectra showed apparent drug incorporation into the polymer matrix of NPs. The encapsulation of BCs enhanced the antioxidative effect. The prepared POS nanoparticles' cytotoxicity was studied using two dermal cell lines, keratinocyte (HaCaT) cells and fibroblasts (HDFn). The nanoparticle cytotoxic effect was more substantial on HaCaT cell lines. A reconstructed human epidermis (RHE) was successfully used to investigate the penetration of polymeric NPs. Based on permeation and histology studies, HC-POS-NPs and CF-POS-NPs were shown not to be suitable for dermal applications with the explored drug concentrations. AD presents a high permeation rate and no toxic impact on RHE.
PubMed: 38931876
DOI: 10.3390/pharmaceutics16060753 -
Toxicon : Official Journal of the... Sep 2023Besides neuronal cells, botulinum neurotoxins (BoNTs) can also affect other cell types such as fibroblasts or keratinocytes. These cells play a key role in skin...
Besides neuronal cells, botulinum neurotoxins (BoNTs) can also affect other cell types such as fibroblasts or keratinocytes. These cells play a key role in skin conditions. Maintaining a high-quality sebum secretion is essential to avoid premature aging. This study explored the effect of abobotulinumtoxinA (aboBoNT-A) in the rhino mouse. Briefly, anaesthetized animals were injected via the intra-dermal route (ID; four sites of injection) by either vehicle or 0.1, 0.3 and 1 Unit aboBoNT-A per mouse. A reference group was administered with adapalene gel 0.1% (daily local application) for 15 days. Adapalene is a third-generation retinoid and is used as first-line treatment of moderate acne. The body weight and the thickness of the dorsal skin were measured on days 1, 5, 10 and 15; erythema and scaling were recorded at the same time. On day 15, animals were ethically euthanized and skin samples were collected for histology, ELISA and lipidomic assays. AboBoNT-A administered ID at the doses 0.1 U and 0.3 U per mouse was well tolerated. 1 U aboBoNT-A (per mouse) induced a transient loss of muscle tone associated with a slight body weight loss after which mice recovered a good health status. AboBoNT-A did not show any significant effect on utricles surface area but induced a significant anti-inflammatory effect on dermis at the two highest doses. Moreover, aboBoNT-A showed neither side effects commonly observed with local retinoids, nor hyperplasia or dermis inflammation. No change in skin Interleukin-1alpha (IL-1α) cytokine levels was evidenced with aboBoNT-A, whereas a dose-dependent increase of substance P (SP) concentration in the skin was recorded, suggesting that aboBoNT-A induces neuropeptide accumulation in tissue by inhibiting exocytosis mechanisms. Lipidomic analysis showed that aboBoNT-A significantly increased the sebum concentration of several lipid species, presenting skin protecting properties. Overall, these data suggest that ID aboBoNT-A has skin rejuvenation, anti-inflammatory and moisture-boosting properties.
Topics: Mice; Animals; Sebum; Skin; Botulinum Toxins, Type A; Retinoids; Adapalene
PubMed: 37517594
DOI: 10.1016/j.toxicon.2023.107230 -
Cell Reports Apr 2022Tendon maturation lays the foundation for postnatal tendon development, its proper mechanical function, and regeneration, but the critical cell populations and the...
Tendon maturation lays the foundation for postnatal tendon development, its proper mechanical function, and regeneration, but the critical cell populations and the entangled mechanisms remain poorly understood. Here, by integrating the structural, mechanical, and molecular properties, we show that post-natal days 7-14 are the crucial transitional stage for mouse tendon maturation. We decode the cellular and molecular regulatory networks at the single-cell level. We find that a nerve growth factor (NGF)-secreting Cd9Cd271 tendon stem/progenitor cell population mainly prompts conversion from neonate to adult tendon. Through single-cell gene regulatory network analysis, in vitro inhibitor identification, and in vivo tendon-specific Shp2 deletion, we find that SHP2 signaling is a regulator for tendon maturation. Our research comprehensively reveals the dynamic cell population transition during tendon maturation, implementing insights into the critical roles of the maturation-related stem cell population and SHP2 signaling pathway during tendon differentiation and regeneration.
Topics: Adapalene; Animals; Cell Differentiation; Mice; Signal Transduction; Stem Cells; Tendons
PubMed: 35476985
DOI: 10.1016/j.celrep.2022.110762 -
Stem Cell Research & Therapy Mar 2021Autologous fat grafting is often a crucial aspect of reconstructive and aesthetic surgeries, yet poor graft retention is a major issue with this technique. Enriching fat...
BACKGROUND
Autologous fat grafting is often a crucial aspect of reconstructive and aesthetic surgeries, yet poor graft retention is a major issue with this technique. Enriching fat grafts with adipose tissue-derived mesenchymal stem cells (AD-MSCs) improves graft survival-however, AD-MSCs represent a heterogeneous population. Selection of subpopulations of AD-MSCs would allow the targeting of specific AD-MSCs that may benefit fat graft survival more than the general AD-MSC population.
METHODS
Human AD-MSCs were selected for the surface marker CD271 using magnetic-activated cell sorting and compared to the CD271 negative phenotype. These subpopulations were analysed for gene expression using Real-Time qPCR and RNA sequencing; surface marker characteristics using immunostaining; ability to form tubules when cultured with endothelial cells; and gene and protein expression of key angiogenic mediators when cultured with ex-vivo adipose tissue.
RESULTS
Human AD-MSCs with the surface marker CD271 express angiogenic genes at higher levels, and inflammatory genes at lower levels, than the CD271- AD-MSC population. A greater proportion of CD271+ AD-MSCs also possess the typical complement of stem cell surface markers and are more likely to promote effective neoangiogenesis, compared to CD271- AD-MSCs.
CONCLUSION
Enriching grafts with the CD271+ AD-MSC subpopulation holds potential for the improvement of reconstructive and aesthetic surgeries involving adipose tissue.
Topics: Adapalene; Adipose Tissue; Cell Differentiation; Cells, Cultured; Endothelial Cells; Humans; Mesenchymal Stem Cells
PubMed: 33653407
DOI: 10.1186/s13287-021-02177-0 -
Frontiers in Pharmacology 2022Although advances in diagnostics and therapeutics have prolonged the survival of triple-negative breast cancer (TNBC) patients, metastasis, therapeutic resistance, and...
Although advances in diagnostics and therapeutics have prolonged the survival of triple-negative breast cancer (TNBC) patients, metastasis, therapeutic resistance, and lack of targeted therapies remain the foremost hurdle in the effective management of TNBC. Thus, evaluation of new therapeutic agents and their efficacy in combination therapy is urgently needed. The third-generation retinoid adapalene (ADA) has potent antitumor activity, and using ADA in combination with existing therapeutic regimens may improve the effectiveness and minimize the toxicities and drug resistance. The current study aimed to assess the anticancer efficacy of adapalene as a combination regimen with the PI3K inhibitor (GDC-0941) in TNBC models. The Chou-Talalay's method evaluated the pharmacodynamic interactions (synergism, antagonism, or additivity) of binary drug combinations. Flow cytometry, Western blotting, and studies were used to analyze the mechanism of GDC-ADA synergistic interactions in TNBC cells. The combination of GDC and ADA demonstrated a synergistic effect in inhibiting proliferation, migration, and colony formation of tumor cells. Accumulation of reactive oxygen species upon co-treatment with GDC and ADA promoted apoptosis and enhanced sensitivity to GDC in TNBC cells. The findings indicate that ADA is a promising therapeutic agent in treating advanced BC tumors and enhance sensitivity to GDC in inhibiting tumor growth in TNBC models while reducing therapeutic resistance.
PubMed: 36003501
DOI: 10.3389/fphar.2022.958443 -
The Journal of Clinical and Aesthetic... Jul 2020We investigated the efficacy and tolerability of nicotinamide cream plus an antibacterial adhesive agent and zinc-pyrrolidone carboxylic acid compared to placebo in...
Efficacy and Tolerability of Topical Nicotinamide Plus Antibacterial Adhesive Agents and Zinc-Pyrrolidone Carboxylic Acid Versus Placebo as an Adjuvant Treatment for Moderate Acne Vulgaris in Indonesia: A Multicenter, Double-blind, Randomized, Controlled Trial.
We investigated the efficacy and tolerability of nicotinamide cream plus an antibacterial adhesive agent and zinc-pyrrolidone carboxylic acid compared to placebo in patients with moderate acne vulgaris (MAV) in Indonesia. This was a multicenter, double-blind, randomized, placebo-controlled, parallel-group study conducted in five teaching hospitals in Indonesia from August 2016 to January 2017. Eligible participants included 140 patients with MAV, aged 12 to 50 years, who were enrolled and randomly divided into two groups to receive either adapalene and the study formulation or adapalene and a placebo cream twice daily for six weeks. Clinical response and treatment efficacy were assessed through acne lesion counts, presence of side effects, and patient satisfaction at the second, fourth, and sixth weeks after the first visit. A total of 140 subjects from five different centers (28 subjects in each center) were enrolled. One hundred twenty-seven subjects completed the study, including 63 subjects in the study group and 64 subjects in the placebo group. A significant decrease in the number of noninflammatory lesions in the second week was noted in the study group compared to in the placebo group. There were no significant differences in adverse effects between the two groups in the second and fourth weeks. Treatment using nicotinamide plus an antibacterial adhesive agent and zinc-pyrrolidone carboxylic acid was effective in reducing noninflammatory lesions by the second week of therapy. ClinicalTrials.gov registration no. NCT0326298.
PubMed: 32983333
DOI: No ID Found -
ELife Aug 2022Single-cell technologies (RNA-sequencing, flow cytometry) are critical tools to reveal how cell heterogeneity impacts developmental pathways. The placenta is a fetal...
Full spectrum flow cytometry reveals mesenchymal heterogeneity in first trimester placentae and phenotypic convergence in culture, providing insight into the origins of placental mesenchymal stromal cells.
Single-cell technologies (RNA-sequencing, flow cytometry) are critical tools to reveal how cell heterogeneity impacts developmental pathways. The placenta is a fetal exchange organ, containing a heterogeneous mix of mesenchymal cells (fibroblasts, myofibroblasts, perivascular, and progenitor cells). Placental mesenchymal stromal cells (pMSC) are also routinely isolated, for therapeutic and research purposes. However, our understanding of the diverse phenotypes of placental mesenchymal lineages, and their relationships remain unclear. We designed a 23-colour flow cytometry panel to assess mesenchymal heterogeneity in first-trimester human placentae. Four distinct mesenchymal subsets were identified; CD73CD90 mesenchymal cells, CD146CD271 perivascular cells, podoplaninCD36 stromal cells, and CD26CD90 myofibroblasts. CD73CD90 and podoplanin + CD36+ cells expressed markers consistent with cultured pMSCs, and were explored further. Despite their distinct ex-vivo phenotype, in culture CD73CD90 cells and podoplaninCD36 cells underwent phenotypic convergence, losing CD271 or CD36 expression respectively, and homogenously exhibiting a basic MSC phenotype (CD73CD90CD31CD144CD45). However, some markers (CD26, CD146) were not impacted, or differentially impacted by culture in different populations. Comparisons of cultured phenotypes to pMSCs further suggested cultured pMSCs originate from podoplaninCD36 cells. This highlights the importance of detailed cell phenotyping to optimise therapeutic capacity, and ensure use of relevant cells in functional assays.
Topics: Adapalene; Biomarkers; CD146 Antigen; Cell Differentiation; Cells, Cultured; Dipeptidyl Peptidase 4; Female; Flow Cytometry; Humans; Mesenchymal Stem Cells; Phenotype; Placenta; Pregnancy; Pregnancy Trimester, First; Thy-1 Antigens
PubMed: 35920626
DOI: 10.7554/eLife.76622 -
Drug Design, Development and Therapy 2022The objective of the present study was to scrutinize the microsponges (MS) as a carrier system using Adapalene (ADA) as a model drug.
PURPOSE
The objective of the present study was to scrutinize the microsponges (MS) as a carrier system using Adapalene (ADA) as a model drug.
METHODS
Data modelling was implemented using Plackett-Burman design to identify the main variables affecting the formulation of ADA-MS. The adopted method of preparation for MS was quasi-emulsion solvent diffusion method. The nominated independent variables were volume of organic phase, sonication time, stirring speed, drug percent, polymer type, emulsifier concentration, and method of organic phase addition. As for the dependent variables, they included entrapment efficiency (E.E.%), production yield (P.Y.%), particle size (P.S.) and morphology. Furthermore, selected ADA loaded microsponges (ADA-MS) were in vitro assayed for their biological activities via cytotoxicity, UVA irradiation and cell viability, and antimicrobial activity.
RESULTS
The study indicated that the drug percent, polymer type and surfactant concentration have the key significant effect on E.E.% and P.Y.%, while, the drug percent, stirring speed and volume of organic phase have had a significant effect on P.S. and their morphology. Furthermore, ADA-MS had a momentous cytotoxic effect on A431 and M10 cell-lines with exceptional enrichment when the polymer Eudragit RS100 was used. Also, the ADA-MS increased the cell viability after UVA irradiation on HFB-4 cell-line by 14% to 43%, especially when using Ethyl Cellulose as a polymer. Lastly, the antimicrobial activity of ADA against was boosted when incorporated into MS.
CONCLUSION
The Plackett-Burman design proved its impact in discerning preparation variables affecting the quality of ADA-MS formulation, with heightening of the in vitro biological activities of ADA. Thus, MS was presumed to be an auspicious carrier system for ADA.
Topics: Adapalene; Drug Delivery Systems; Emulsions; Excipients; Polymers; Anti-Infective Agents
PubMed: 36388080
DOI: 10.2147/DDDT.S383051