Adapalene Research Articles

Pulse Activation of Retinoic Acid Receptor Enhances Hematopoietic Stem Cell Homing by Controlling CXCR4 Membrane Presentation.

The interplay between metabolic signaling and stem cell biology has gained increasing attention, though the underlying molecular mechanisms remain incompletely elucidated. In this study, we identify and characterize the role of adapalene (ADA), a retinoic acid receptor (RAR) agonist, in modulating the migration behavior of hematopoietic stem cells (HSCs). Our initial findings reveal that ADA treatment suppresses hematopoietic stem and progenitor cell (HSPC) mobilization induced by AMD3100 and G-CSF. Furthermore, we demonstrate that ADA treatment upregulates the surface expression of CXCR4 on HSPCs, resulting in enhanced chemotaxis towards CXCL12. Mechanistically, our study suggests that ADA enhances CXCR4 surface presentation without increasing CXCR4 mRNA levels, pointing towards a non-canonical role of RAR signaling in regulating intracellular trafficking of CXCR4. In vivo experiments show that ADA administration significantly enhances HSC homing efficiency. Additionally, competitive transplantation assays indicate a marked increase in donor chimerism following ADA treatment. These findings highlight the critical role of retinoic acid signaling in regulating HSC homing and suggest its potential for advancing novel HSC-based therapeutic strategies.

Adapalene as a chemical sensor for sensitive determination of manganese

ABSTRACT The work describes the use of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2- naphthoic acid, or Adapalene (ADP) as a fluorescence tagging reagent, in a straightforward and very specific spectrofluorometric approach for the trace measurement of manganese (VII) in water. The process is based on the redox interaction of ADP with manganese (VII) in an acidic solution, which forms the complex [Mn (II)-ADP] and causes fluorescence at λex max/λem max = 323/400 nm. High-intensity fluorescence at 400 nm was seen in the fluorescence spectra of the formed complex ion association, Mn (II)-ADP, at pH 4. 1.55 µg mL−1 was the quantification limit, and 0.51 µg mL−1 was the detection limit and the correlation coefficient (R2) was 0.9863. 1.2173 L mol−1 was determined to be the Stern-Volmer. Spectrofluorometric technique is used to validate the approach in environmental water samples, yielding reasonable recovery percentages (89–93%). The current approach is advised to be used for reliable and accurate assessment of manganese (VII) in all wastewater and seawater samples, without the need for complex instrumentation and lengthy procedures.

Chemometrics‐Empowered Optimization of a Reliable Reversed Phase–High Performance Liquid Chromatography Method for the Simultaneous Estimation of Erythromycin and Adapalene in Pharmaceutical Nanoformulation

ABSTRACTAn innovative, simple, economical, and sensitive reversed phase–high performance liquid chromatography (RP–HPLC) chromatographic method for simultaneous analysis of erythromycin (ERY) and adapalene (ADP) in bulk and pharmaceutical nanoformulation was developed by analytical quality‐by‐design (AQbD) avenue. According to published research, there is no strategy that integrates RP–HPLC with AQbD for estimating ERY and ADP. The analysis was carried out with Box–Behnken design, which reduced trial runs and design points. Acetonitrile: orthophosphoric acid (OPA) (0.1% triethanolamine) in pH 6.2 water was used as the mobile phase. The ratio was set to 35:65 (v/v) at 0.8 mL/min flow rate to detect the analytes at 231 nm. As per the guidelines in International Conference on Harmonization Q1A (R2), the developed approach was validated. ERY and ADP regression coefficients (r2) were found to be 0.9998 and 0.9999, respectively, over 5–25 µg/mL range. Validation parameters comprising linearity, sensitivity, system suitability, precision, robustness, and accuracy were performed. To assess stability, the drugs were subjected to stress conditions (hydrolytic, oxidative, thermal, and photolytic), and drugs were most vulnerable to degrade in alkaline and oxidative conditions. A new technique successfully analyzed novel drug carriers loaded with ERY and ADP.

Development and validation of stability indicating HPLC-DAD assay of adapalene, methylparaben and propylparaben in a cosmeceutical gel matrix with blueness, greenness and whiteness assessment via relative ranking: An ab initio-sub finem juxtaposed non-traditional approaches

Adapalene (ADA) is primarily used as a cosmeceutical gel in the treatment of mild-moderate acne and is also used off-label to treat keratosis pilaris as well as other skin conditions. A stability-indicating fit-for-purpose (FFP) method has been developed for co-determination of ADA, methylparaben (MPN), and propylparaben (PPN) combined in a cosmeceutical gel dosage form. This method was based on a reversed-phase RP-HPLC separation of the cited analytes. It avoided the use of tetrahydrofuran (THF), which is commonly used by both compendial and published procedures for determination of ADA, thus improving method blueness (applicability), greenness and whiteness. The method development and validation followed non-traditional eco-friendly approaches including chemical simulations and empirical modelling. The HPLC separation was performed on an RP Zorbax Eclipse XDB-C8 analytical column [150 × 4.6 mm, 5 µm (80 Å)] with gradient elution system of HPLC grade acetonitrile and 50 mM aqueous sodium dihydrogen phosphate buffer containing 5 mM ethylenediaminetetraacetic acid (EDTA) adjusted to pH 8.0 as the mobile phase at a flow rate of 2.5 mL min−1 and column oven was set at 25 °C. EDTA played an important role for reproducibility of retention time of the three analytes especially for ADA. It controlled deprotonation of the three acidic analytes under study and hence reproduce their ionization, hydrophobicity, and hence retention time. Quantitation was achieved with the photodiode array detection (DAD) at wavelengths of 256 nm for both MPN and PPN and 312 nm for ADA. Target Measurement Uncertainty (TMU) for the three analytes was determined via two approaches; misclassification rates approach employing 100,000 Monte Carlo simulations (MCS) and in-specification probability (ISP) to ascertain fitness-for-purpose of the proposed method. Microsoft Excel workbooks were developed for both TMU calculation approaches in addition to calculation of procedure capability index (Ppk) and sigma level for each analyte and attached in the Supplementary material. Moreover, linearity of the method underwent additional assessment using the previously mentioned TMU and procedure capability determination techniques. The robustness of the method was checked using Plackett-Burman experimental design (PBD) as an empirical modelling technique which was examined thoroughly to detect some interactions. The calibration graphs for each drug were rectilinear in the range of 0.34–7.08, 0.38–7.00 and 0.08–1.75 µg mL−1 for ADA, MPN, and PPN, respectively. The stress testing revealed photostability of the three components and variable degrees of degradation in the other conditions. The proposed HPLC-DAD method was successfully validated and applied for the determination of the investigated analytes in a gel matrix. In addition, method blueness and greenness were comparatively evaluated via very recent approaches of Blue Applicability Grade Index (BAGI), Green Solvents Selection Tool (GSST), Spider Diagram for Assessment of the Green Analytical Index (SDAGI), Analytical Method Greenness Score (AMGS), Carbon Footprint (CF), Modified Complementary Green Analytical Procedure Index (ComplexMoGAPI), and Analytical GREEnness Metric Approach (AGREE). Furthermore, the method whiteness was assessed via Red Green Blue Twelve (RGB 12) model following a relative ranking approach.

Design and Biocompatibility of Biodegradable Poly(octamethylene suberate) Nanoparticles to Treat Skin Diseases.

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.

Multidimensional role of adapalene in regulating cell death in multiple myeloma.

Multiple myeloma (MM) remains a challenging condition to cure, with persistent drug resistance negating the benefits of treatment advancements. The unraveling complexities in programmed cell death (PCD), inclusive of apoptosis, autophagy, and ferroptosis, have highlighted novel therapeutic avenues. Our study focuses on deciphering how adapalene (ADA), a small molecule compound, accelerates the demise of MM cells via targeting their compensatory survival mechanisms. To assess the impact of ADA on MM, we employed flow cytometry and trypan blue exclusion assays to determine cell viabilities across MM cell lines and primary patient samples post-treatment. To delineate ADA's therapeutic targets and mechanisms, we conducted RNA sequencing (RNA-seq), gene set enrichment analysis (GSEA), molecular docking, and molecular dynamics simulations. We further designed pre-clinical trials emphasizing MM, exploring the efficacy of ADA as a standalone and in combination with bortezomib (BTZ). ADA elicited a dose-responsive induction of MM cell death. Building upon ADA's anti-MM capabilities as a single agent, we proposed that ADA-BTZ co-treatment might amplify this lethality. Indeed, ADA and BTZ together greatly potentiated MM cell death. ADA proved beneficial in restoring BTZ susceptibility in BTZ-resistant relapsed or refractory MM (RRMM) patient cells. Molecular simulations highlighted ADA's high affinity (-9.17kcal/mol) for CD138, with MM-GBSA revealing a binding free energy of -27.39kcal/mol. Detailed interaction analyses indicated hydrogen-bonding of ADA with CD138 at the Asp35 and Gln34 residues. Additionally, ADA emerged as a versatile instigator of both ferroptosis and apoptosis in MM cells. Furthermore, ADA disrupted activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway triggered by BTZ, fostering cell death in BTZ-resistant MM subsets. ADA demonstrates a comprehensive capability to orchestrate MM cell death, exerting pronounced anti-MM activity while disrupting NF-κB-related drug resistance. ADA sensitization of MM cells to BTZ unravels its potential as a novel therapeutic drug for MM management.

Development and Characterization of Adapalene Loaded Microemulsion-Based Hydrogel for Acne Treatment Adapalene Microemulsion

Presently, acne is affecting globally many people (9.4%) and one of the leading causes of stress especially in youths. Adapalene (AD) has been applied successfully for acne treatment. However, adapalene drug is from BCS class II and exhibits less solubility in water (<1mg/mL) & causes skin irritation which leads to patient incompliance. The objective of the current study was design of microemulsion-based gel for topical delivery of adapalene. Solubility studies demonstrated that adapalene exhibit good solubility in Tween 80, propylene glycol, and oleic acid. The microemulsion showed globule size 248.4±2 nm, PDI (0.251), and Zeta potential (-15.8 mV) confirming colloidal stability. The dilutability and freeze-thaw study of microemulsion showed no sign of phase separation. The microemulsion-based gel showed clarity, pH (5±0.5), viscosity (64cps), and good spreadability (6.5±0.6 cm) for topical application. In-vitro gel formation study showed that inclusion of polymer (Carbopol 940) maintained viscosity of microemulsion-based hydrogel for longer period of time. Dissolution study demonstrated that AD showed sustained release for 24h from gel as compared to microemulsion and drug suspension. Thus, it could be a prospective formulation for acne treatment via topical route which can improve patient compliance by reducing skin irritation.

Screening of Adapalene Microsponges Fabrication Parameters with Insight on the In vitro Biological Effectiveness.

The objective of the present study was to scrutinize the microsponges (MS) as a carrier system using Adapalene (ADA) as a model drug. 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. 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 Propionibacterium acnes was boosted when incorporated into MS. 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.

Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941.

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 in vitro models. The Chou–Talalay’s method evaluated the pharmacodynamic interactions (synergism, antagonism, or additivity) of binary drug combinations. Flow cytometry, Western blotting, and in silico 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.

Electrostatically optimized adapalene-loaded emulsion for the treatment of acne vulgaris.

Adapalene (AD) is an FDA-approved drug that shows good therapeutic efficacy for the treatment of acne vulgaris. However, due to its negative charge, AD cannot efficiently penetrate across the also negatively-charged skin membrane. This study is the first to assess the treatment of acne vulgaris using electrostatically optimized AD emulsions prepared using anionic AD with methoxy polyethylene glycol-b-poly(ε-caprolactone) (MC) as an anionic emulsifier coupled with a newly synthesized MC with different contents of an amine pendant-group (MC-[NH2]x) as a cationic emulsifier. The AD emulsion prepared using MC-[NH2]x with high cationic charge potential was significantly stable in the short-term studies compared with anionic MC or no emulsifier. Furthermore, the AD emulsion prepared with the cationic MC-[NH2]x emulsifier provided a two or three times stronger therapeutic effect against acne vulgaris than the AD emulsion prepared with the anionic MC emulsifier or no emulsifier in an animal study. Additionally, the AD emulsion with high cationic charge potential exerted a remarkable inhibition of macrophage expression, as confirmed by histological analysis. Therefore, the electrostatic interaction between the negatively-charged skin membrane and the AD emulsion prepared with the cationic MC-[NH2]x emulsifier provides a promising therapeutic strategy for acne vulgaris.

Novel Formulation for Facial Acne using Liposomal Gel Containing Lipid Soluble Naphthoic Acid Derivative

Abstract: The first line therapies in many acne diagnoses include application of retinoic acid derivatives for improvement in acne severity. Though, it has been observed that, current available formulations are sensitive to skin and requires to be applied after repeated time to prolong the action of the medicament at the local layers. To overcome this major downside, in the present investigation the Adapalene (AD) being entrapped into the lipid layers of the liposomes (LUVs) to provide the sustain release and also to bypass the main adverse effect of the retinoic acid derivatives of being toxic if absorbed into blood stream. Aim: To prepare and evaluate the liposomal adapalene for sustain release effect and entrapment into skin layers. Materials and Methods: To prepare the LUVs by film hydration method various lipid polymers are being utilised like DMPG, DPPG, HSPC, and cholesterol. Prepared LUVs were optimized on the basis of particle size, entrapment efficiency. The batch with highest entrapment efficiency (66.18%) and particle size range of 1000nm was further incorporated into (5%) HPMCk4M gel to avail the application compliance in the patient. This formulation was studied for viscosity, pH, Drug content, Spreadability study, in vitro drug release pattern of the dosage form, ex-vivo skin retention study in the layers of skin. Results: The result of the in-vitro release study showed only 28% of drug release which is beneficial for follicular delivery as well as sustained release of the AD. Conclusion: This can be concluding that, AD liposomal gel can be potential solution to the adverse reaction of the current marketed formulation with insights of providing low frequency of application and improved skin health in the acne prone patients. Key words: Liposomal gel, Adapalene, Ex-vivo skin retention study, % entrapment efficiency, in-vitro drug release study.

Adapalene induces adipose browning through the RARβ-p38 MAPK-ATF2 pathway.

Adipose browning has recently been reported to be a novel therapeutic strategy for obesity. Because the retinoic acid receptor (RAR) is a potential target involved in browning, adapalene (AD), an anti-acne agent with RAR agonism, was examined in detail for its effects on adipose browning and the underlying mechanisms in vitro and in vivo. AD upregulated the expression of adipose browning-related markers in a concentration-dependent manner, promoted mitochondrial biogenesis, increased oxygen consumption rates, and lowered lipid droplet sizes in differentiated 3T3/L1 white adipocytes. Among the three retinoic acid receptors (RARα, RARβ, and RARγ), knockdown of the gene encoding RARβ mitigated AD-induced adipose browning. Similarly, LE135 (a selective RARβ antagonist) attenuated AD action, suggesting that AD promotes adipose browning through RARβ. Sequential phosphorylation of p38 mitogen-activated protein kinase (MAPK) and activating transcription factor 2 (ATF2) was critical for AD-induced adipose browning, based on the observations that either SB203580 (a p38 MAPK inhibitor) or ATF2 siRNA reduced the effects of AD. In vivo browning effects of AD were confirmed in C57BL/6J mice and high-fat diet-induced obese (DIO) mice after oral administration of AD either acutely or chronically. This study identifies new actions of AD as an adipose browning agent and demonstrates that RARβ activation followed by increased phosphorylation of p38 MAPK and ATF2 appears to be a key mechanism of AD action.

Adapalene Inhibits Prostate Cancer Cell Proliferation In Vitro and In Vivo by Inducing DNA Damage, S-phase Cell Cycle Arrest, and Apoptosis

Aims: Prostate cancer is a well-known aggressive malignant tumor in men with a high metastasis rate and poor prognosis. Adapalene (ADA) is a third-generation synthetic retinoid with anticancer properties. We investigated the anti-tumor activity and molecular mechanisms of ADA in the RM-1 prostate cancer cell line in vivo and in vitro. Methods: The effects of ADA on cell proliferation were estimated using the CCK-8 and colony formation assays. The wound-healing assay and the Transwell assay were employed to examine the migratory capacity and invasiveness of the cells. Flow cytometry was utilized to evaluate the cell cycle and apoptosis, and Western blotting analysis was used to assess the expression of the associated proteins. Micro-CT, histomorphological, and immunohistochemical staining were used to assess the effects of ADA on bone tissue structure and tumor growth in a mouse model of prostate cancer bone metastasis. Result: ADA dramatically inhibited cell proliferation, migration, invasiveness, and induced S-phase arrest and apoptosis. ADA also regulated the expression of S-phase associated proteins and elevated the levels of DNA damage markers, p53, and p21 after ADA treatment, suggesting that the anti-tumor effect of ADA manifests through the DNA damage/p53 pathway. Furthermore, we observed that ADA could effectively inhibited tumor growth and bone destruction in mice. Conclusion: ADA inhibited prostate cancer cell proliferation, elicited apoptosis, and arrested the cell cycle in the S-phase. ADA also slowed the rate of tumor growth and bone destruction in vitro. Overall, our results suggest that ADA may be a potential treatment against prostate cancer.

Dermal delivery and follicular targeting of adapalene using PAMAM dendrimers.

Acne is a chronic dermatological disease of pilosebaceous units existing in the form of hair follicles (HFs) and accompanying sebaceous glands. In topical acne treatment, localisation of drug substance at the target site, in pilosebaceous units, especially in HFs is essential. The aims of this study were to develop and optimise adapalene (ADA)-loaded PAMAM dendrimer-based nanocarriers for topical acne treatment and to prepare gel formulations of the selected nanocarriers and to characterise their rheological properties and spreadability. ADA accumulation in HFs and in the skin from PAMAM dendrimers' aqueous colloidal formulations and their gel formulations were quantitatively determined using punch biopsy technique. Follicular targeting efficiency from PAMAM dendrimers and their gel formulation was compared with the commercial gel product, Differin® Gel. The localisation of fluorescently labelled PAMAM dendrimers was visualised usinga confocal microscope, which confirmed a successful delivery of the carrier system to the HFs. It was also quantified that PAMAM dendrimers improved follicular localisation and skin deposition of ADA. PAMAM dendrimers' gel formulation including lower ADA doses compared with the commercial product exhibited efficient performance in terms of drug accumulation in HFs. In vitro cell viability studies showed the relative safety of G2-PAMAM dendrimers which could be considered to possibly be well tolerated by the skin. Overall, PAMAM dendrimers' potential to selectively target drugs to the site of action, reduce dose administrated, therefore minimise side effects and provide efficiency in topical treatment of dermatological diseases such as acne was shown.

Preparation and evaluation of adapalene nanostructured lipid carriers for targeted drug delivery in acne

Adapalene (ADA) is believed to be one of the topical treatments utilized commonly in case of acne. Nanostructured lipid carriers (NLCs) have been established as an effective carrier system with certain advantages, for instance increased solubility, drug targeting, controlled drug release, and stability of ADA. This study was conducted to obtain the formulation with a good therapeutic property. All formulations were formed by probe sonicator and its characterizations were analyzed. Finally, the therapeutic effects of 0.1% ADA-loaded nanostructured lipid carriers (NLC-ADA) were evaluated. This formulation had a great entrapment efficiency (EE) that illustrated a controlled drug release profile. A pilot clinical evaluation conducted on 15 patients (age 25.23 ± 12.24 years) with mild to moderate acne vulgaris lesions. The results demonstrated significant reduction in acne severity index and the number of inflammatory and noninflammatory lesions after 12 weeks of treatment (P-value .02, .04, and .01, respectively). Subjective results were confirmed with significant improvement in size and intensity of porphyrin production in pilosebaceous follicles (P-value = .03). The study demonstrated that the formulation was safe and revealed the proper improvement rate of acne lesions after 12 weeks.

Topical 0.1% adapalene gel versus 0.1% adapalene and 2.5% benzoyl peroxide combination gel in the treatment of mild-to-moderate acne vulgaris: An open-label randomized controlled pilot study

Introduction: The combination of adapalene (ADA) benzoyl peroxide (BPO) offers a safe and effective alternative avoiding long-term antibiotic use in the management of acne vulgaris. Aims: The aim of this study was is to compare the clinical efficacy and tolerability of 0.1% ADA with combination of 0.1% ADA and 2.5% BPO in the treatment of mild-to-moderate acne vulgaris. Methods: All patients were instructed to apply the given topical medications to whole face, excluding lips and eyelids, once a day at night after washing and moistening the facial skin. Follow-up was done once every 4 weeks up to 12 weeks from the start of treatment. Efficacy of treatment arms was assessed by 4 parameters, namely percentage change of total lesion counts (TLCs), Acne severity index, success rate, and response rate. Statistical analysis was performed using the SPSS software version 16.0. Data were analyzed using the Chi-square test, Fisher's exact test, and Mann–Whitney U test. P < 0.05 was considered to indicate statistical significance. Results: Thirty-eight patients were in Group A (ADA-BPO) and 38 patients in Group B (ADA alone). At the end of 12 weeks, Group A had significantly less TLC as well as significant percentage change in total lesions than Group B. Group A was significantly better than Group B in TLC response rate also. Conclusions: The combination gel of 0.1% ADA and 2.5% BPO was superior to 0.1% ADA gel in terms of efficacy. Tolerability was comparable for both the drugs.

Recent Advances Regarding the Therapeutic Potential of Adapalene.

Adapalene (ADP) is a representative of the third retinoids generation and successfully used in first-line acne treatment. ADP binds to retinoic acid nuclear receptors. The comedolytic, anti-inflammatory, antiproliferative, and immunomodulatory are the known ADP effects. Its safety profile is an advantage over other retinoids. ADP recently was found to be effective in the treatment of several dermatological diseases and photoaging besides the utility in the treatment of acne vulgaris. New biological effects of adapalene with therapeutic potential are highlighted in this review paper. Thus, adapalene could be a valuable therapeutic drug into the treatment of several types of cancer. Additionally, some neurodegenerative diseases could be treated with a suitable formulation for intravenous administration. The antibacterial activity against methicillin-resistant Staphylococcus aureus of an analogue of ADP has been proven. In different therapeutic schemes, ADP is more effective in combination with other active substances. New topical combinations with adapalene include ketoconazole (antifungal), mometasone furoate (anti-inflammatory corticosteroid), nadifloxacin (fluoroquinolone), and alfa and beta hydroxy acids. Combination with oral drugs is a new trend that enhances the properties of topical formulations with adapalene. Several studies have investigated the effects of ADP in co-administration with azithromycin, doxycycline, faropenem, isotretinoin, and valganciclovir. Innovative formulations of ADP also aim to achieve a better bioavailability, increased efficacy, and reduced side effects. In this review, we have highlighted the current studies on adapalene regarding biological effects useful in various treatment types. Adapalene has not been exploited yet to its full biological potential.

Ion Pair Strategy in Solid Lipid Nanoparticles: a Targeted Approach to Improve Epidermal Targeting with Controlled Adapalene Release, Resulting Reduced Skin Irritation.

Adapalene (AD) is one of the main retinoids used in the topical therapy of acne, an extremely common skin disease usually associated with psychological morbidity. However, like other retinoids, AD is frequently associated with skin irritation. To overcome the skin irritation, we proposed the encapsulation of AD in solid lipid nanoparticles (SLNs) using the ion pair strategy. The developed SLN-AD was characterized by high-performance liquid chromatography, differential scanning calorimetry, X-ray diffraction, synchrotron small-angle X-ray scattering, and transmission electron microscopy. In vitro permeation tests using porcine skin and in vivo mice skin irritation test were performed to evaluate, respectively, the drug's skin distribution and the skin irritation. The characterization studies were able to demonstrate that the proposed strategy effectively provided high AD encapsulation in SLNs and its incorporation into a hydrophilic gel. Sustained release, epidermal targeting, and less skin irritation were observed for SLN-AD gel in comparison to the marketed AD gel. The studies demonstrated that the encapsulation of AD in SLNs through the formation of an ion pair is a valuable alternative to diminish the adverse skin reactions caused by AD and can optimize patient adherence to treatment.

Development and validation of a HPLC method for simultaneous quantitative determination of adapalene and benzoyl peroxide in gel products

Adapalene (AP) and Benzoyl peroxide (BO) have been used to treat acnes very efficient for many years, especially in gel products. But nowaday, that gel products still don't have in-house standard. And furthermore, the most difficult thing to build in-house standard is to assay simultaneously. The aim of this research is to build a method to assay two of AP and BO simultaneously by HPLC method. Subjects: AP (from India) and BO (from China). Solvents get the quality standard to use in liquid chromatography. Sample: gel product (AP 0.1% and BO 2.5%) prepared at Laboratory of School of Medicine, National University of HCMC. Chromatographic system: HPLC Shimadzu system with column C18 RP (250 x 4.6 mm; 5 mm), injection volumn 20 mL, detector at 270 nm, flow rate 1 mL/min, temperature 30oC, mobile phase with acetonitril - tetrahydrofuran - acid formic 0.1% in water 42 : 32 : 26. Validations: system suitability, specificity, linearity, accuracy, precision adapt to ICH. Results: The HPLC method for simultaneous quantitative determination of adapalene and benzoyl peroxide in gel products was built successfully. The method was achieved all validations term adapt to ICH: system suitability, specificity, linearity, accuracy, precision. Furthermore, that method is used to assay the concentration of two API (AP and BO) in the product (prepared at Laboratory of School of Medicine, National University of HCMC) with result: the concentration of AP is 101.38 0.87% and that of BO is 95.56 0.04 %, get the standard of USP 41.

Advanced development of a non-ionic surfactant and cholesterol material based niosomal gel formulation for the topical delivery of anti-acne drugs

The aim of the present investigation was to develop adapalene (ADP), a high lipophilicity and low solubility anti-acne drug-loaded niosomal topical gel formulation, in order to improve its therapeutic efficacy.