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Scientific Reports Jan 2024In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box-Behnken design 3. The...
In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box-Behnken design 3. The independent variables, Eudragit RS100 percentage in the polymer mixture, organic phase volume, and drug to polymer percentage, were explored. The optimized formulation exhibited remarkable characteristics, with a 98.3% ± 1.6 production yield, 97.3% ± 1.64 entrapment efficiency, and a particle size of 31.8 ± 1.1 µm. Notably, it achieved a 24 h cumulative drug release of 75.1% ± 1.4. To delve deeper into its efficacy, we evaluated the optimized microspongeal-gel in vitro, in vivo, and clinically. It demonstrated impressive retention in the pilosebaceous unit, a target for acne treatment. Comparative studies between our optimized Adapalene microspongeal gel and marketed Adapalene revealed superior performance. In vivo studies on Propionibacterium acnes-infected mice ears showed a remarkable 97% reduction in ear thickness, accompanied by a significant decrease in inflammatory signs and NF-κB levels, as confirmed by histopathological and histochemical examination. Moreover, in preliminary clinical evaluation, it demonstrated outstanding effectiveness in reducing comedonal lesions while causing fewer irritations. This not only indicates its potential for clinical application but also underscores its ability to enhance patient satisfaction, paving the way for future commercialization.
Topics: Humans; Mice; Animals; Adapalene; Acne Vulgaris; Skin; Polymers; Dermatologic Agents; Treatment Outcome; Gels
PubMed: 38228631
DOI: 10.1038/s41598-024-51392-1 -
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 -
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 -
The Journal of Clinical and Aesthetic... Oct 2021Actinic keratoses (AKs) are sun-induced cutaneous lesions that may progress to squamous cell carcinoma (SCC). Photodynamic therapy (PDT) is an ideal treatment option for...
BACKGROUND
Actinic keratoses (AKs) are sun-induced cutaneous lesions that may progress to squamous cell carcinoma (SCC). Photodynamic therapy (PDT) is an ideal treatment option for AKs because it allows for treatment of field cancerization, selective destruction of diseased tissue, good cosmetic outcomes, and limited downtime.
OBJECTIVES
This study sought to determine the efficacy and safety of pretreating AKs of the dorsal hands and forearms with adapalene gel, an inexpensive and over-the-counter retinoid, prior to debridement of the target area and PDT with aminolevulinic hydrochloride acid (ALA, 10%) gel and narrowband red light.
METHODS
Fifteen patients with AK lesions of the right or left dorsal hands or forearms were pretreated with adapalene gel (0.1%) twice daily for one week prior to ALA-PDT. The other hand or forearm was treated with ALA-PDT (standard therapy), but not pretreated. For PDT, all treated areas were debrided with sandpaper, degreased with acetone, incubated for one hour with 10% ALA gel under occlusion, and illuminated with narrowband red light (~635 nm). All patients experienced one PDT treatment session.
RESULTS
Eight weeks after treatment, 12 subjects in the adapalene-pretreated group achieved 50% to 100% clearance compared to 10 subjects in the standard therapy group. The median lesion count reduction in the adapalene-pretreated group was -79% compared to -57% in the standard therapy group, and this difference was significant (=0.0164). The treatment was well-tolerated and the level of patient satisfaction was high.
CONCLUSIONS
Pretreatment with adapalene gel twice daily for one week may enhance efficacy in a single ALA-PDT treatment of AK lesions of the dorsal hand or forearm.
PubMed: 34976284
DOI: No ID Found -
Clinical, Cosmetic and Investigational... 2011Acne vulgaris is a chronic disease with several pathogenic factors. Multiple medications are typically used that can lead to nonadherence and treatment failure....
BACKGROUND
Acne vulgaris is a chronic disease with several pathogenic factors. Multiple medications are typically used that can lead to nonadherence and treatment failure. Combination medications target multiple pathways of acne formation and may offer therapeutic benefit.
PURPOSE
To explore the efficacy and tolerability of combination retinoid plus antimicrobial treatments in acne vulgaris.
METHODS
A PubMed and Google search was conducted for combination therapies of clindamycin and tretinoin, with secondary analysis of related citations and references. Similar searches were completed for the combination medications of benzoyl peroxide plus clindamycin or erythromycin, and for the combination therapy of adapalene and benzoyl peroxide.
RESULTS
Combination clindamycin phosphate and tretinoin gel was found to be more efficacious than monotherapy of either drug or its vehicle for acne, including inflammatory acne, and has a greater onset of action than either drug alone. Clindamycin phosphate and tretinoin gel was well-tolerated, and adherence to its use exceeded that of using both medications in separate formulations. Benzoyl peroxide-containing combination medications with clindamycin or erythromycin were both more effective in the treatment of acne than either drug alone. Both medications were well-tolerated, with dry skin being the most common adverse effect.
CONCLUSIONS
Combination medications have superior efficacy and adherence, and have a similar tolerability profile compared with monotherapy of its components. Several studies have found antibiotic-containing combination products with a retinoid effective for acne. The use of antibiotic-containing combination medications for acne can lead to bacterial resistance. Due to this potential for bacterial resistance, benzoyl peroxide treatments are also recommended in combination with a retinoid.
PubMed: 21760743
DOI: 10.2147/CCID.S13873 -
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 -
JAMA Dermatology Feb 2019Genetic testing results can provide guidance in developing personalized treatment plans for patients with vascular anomalies.
IMPORTANCE:
Genetic testing results can provide guidance in developing personalized treatment plans for patients with vascular anomalies.
OBJECTIVE:
To explore the efficacy of tramitinib in the treatment of an extracranial arteriovenous malformation with a somatic mutation.
DESIGN:
Case report of a child with an arteriovenousu malformation that was successfully treated with trametinib after identification of a specific somatic mutation within the malformation.
SETTING:
Outpatient Vascular Anomalies Clinic, Stanford University, Stanford, CA.
PARTICIPANT:
An 11-year-old girl with an arteriovenous malformation on the back who had failed treatment with systemic sirolimus.
INTERVENTION:
Paired exome sequencing using tumor and saliva DNA was performed and identified a somatic mutation within the gene. The patient was then transitioned to trametinib at a starting dose of 0.5 mg once daily then increased to 0.5 mg twice daily after one month.
MAIN OUTCOME:
Tramitinib was effective in reducing the size of and blood flow to the arteriovenous malformation.
RESULTS:
After one month on tramitinib, the patient and parents noticed the malformation reduced in size and became lighter in color. After six months of treatment, quantitative analyses were performed using magnetic resonance imaging and showed significant interval decrease in the volume of the malformation and the caliber of the vasculature compared to prior examinations. To date, she has tolerated the treatment well with development of a mild acneiform eruption responding well to over the counter adapalene and benzoyl peroxide.
CONCLUSION AND RELEVANCE:
Management of arteriovenous malformations is very challenging due to almost inevitable disease progression and high recurrence rates after surgical resection. The discovery of a somatic mutation associated with this arteriovenous malformation provided guidance for targeted therapy. Trametinib may be a promising targeted therapeutic option for sporadic extracranial arteriovenous malformations harboring mutations.
Topics: Arteriovenous Malformations; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Genotype; Humans; Microtubule-Associated Proteins; Molecular Targeted Therapy; Pyridones; Pyrimidinones; Severity of Illness Index; Thoracic Wall; Treatment Outcome
PubMed: 30566190
DOI: 10.1001/jamadermatol.2018.4653 -
The British Journal of Dermatology Oct 1998A multicentre study was conducted to compare clinical safety and efficacy of adapalene 0.1% solution and tretinoin 0.025% gel, both topical treatments for acne, in a... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A multicentre study was conducted to compare clinical safety and efficacy of adapalene 0.1% solution and tretinoin 0.025% gel, both topical treatments for acne, in a once-daily dosage regimen for 12 weeks. A total of 297 patients were enrolled by eight investigators in this randomized, investigator-masked study in a parallel group design. An open label period using adapalene followed this study to assess the long-term safety of adapalene solution. Adapalene and tretinoin proved to be clinically and statistically effective in treating acne by reducing inflammatory (47% and 50%, respectively) and non-inflammatory lesions (57% and 54%) as compared to baseline. When comparing patients who had 75% or greater improvement in open comedones, adapalene was shown to be significantly more effective than tretinoin. No serious adverse event was reported during this study, including during the long-term period. The reactions that occurred were similar between treatments, i.e. burning, pruritus, scaling, dryness and erythema.
Topics: Acne Vulgaris; Adapalene; Administration, Topical; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Child; Double-Blind Method; Drug Eruptions; Female; Gels; Humans; Keratolytic Agents; Male; Naphthalenes; Treatment Outcome; Tretinoin
PubMed: 9990420
DOI: 10.1046/j.1365-2133.1998.1390s2041.x