ADMET and DMPK最新文献

{"title":"Naringin prevents heart mitochondria dysfunction during diabetic cardiomyopathy in rats.","authors":"Ilya B Zavodnik, Tatsiana A Kavalenia, Siarhei N Kirko, Elena B Belonovskaya, Irina A Kuzmitskaya, Yulia V Eroshenko, Elena A Lapshina, Vyacheslav U Buko","doi":"10.5599/admet.2571","DOIUrl":"10.5599/admet.2571","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cardiac mitochondria dysfunction plays a central pathophysiological role in the abnormal glucose metabolism in the heart during diabetic cardiomyopathy. The present study evaluated the effects of flavonoid glycoside naringin treatment on the interconnection between changes in cardiac mitochondria oxygen consumption, membrane potential and mitochondrial Ca²⁺ sensitivity during type 1 diabetes.</p><p><strong>Experimental approach: </strong>Type 1 diabetes was induced by an intraperitoneal injection of streptozotocin (40 mg/kg) in rats and islet morphology, glucose and insulin levels, changes in heart mitochondria respiration, membrane potential, spontaneous and Ca²⁺ - induced mitochondrial permeability transition (MPT) pore opening were evaluated.</p><p><strong>Key results: </strong>Diabetes resulted in typical signs of hyperglycaemia, which were accompanied by a rat cardiac mitochondria dysfunction, manifested by decreased <i>V</i> ₂ and <i>V</i> ₃ rates of oxygen consumption, while the initial membrane potential value remained unchanged. The rates of Ca²⁺-induced MPT pore opening and Ca²⁺-induced membrane potential dissipation in isolated mitochondria decreased under type 1 diabetes. The naringin treatment (40 mg/kg of the body weight, 4 weeks) partially recovered impaired cardiac mitochondria respiration, decreased spontaneous and increased Ca²⁺-induced MPT pore opening, improved pancreatic islets morphology and dystrophic changes, lowered glycated haemoglobin and blood plasma urea, and decreased the oxidative stress level with glucose or insulin concentrations remaining unchanged in diabetic animals.</p><p><strong>Conclusions: </strong>Naringin administration demonstrated beneficial effects during type 1 diabetes and represents a promising therapeutic (or nutraceutical) approach for diabetes treatment.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 1","pages":"2571"},"PeriodicalIF":3.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrochemical sensor based on multi-walled carbon nanotubes and two-dimensional zeolitic imidazolate framework nanosheets: Application in determining dacarbazine.","authors":"Somayeh Tajik, Hadi Beitollahi, Fariba Garkani Nejad, Zahra Dourandish, Samuel Adeloju","doi":"10.5599/admet.2617","DOIUrl":"10.5599/admet.2617","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cancer is a serious public health concern, hence the determination of dacarbazine as a significant chemotherapeutic agent is very important.</p><p><strong>Experimental approach: </strong>In the present work, we use a facile method to synthesize a nanocomposite of multi-walled carbon nanotubes (MWCNTs) and two-dimensional zeolitic imidazolate framework nanosheets (2D ZIF-L NSs). The resulting MWCNTs/2D ZIF-L NSs nanocomposite was characterized by field-emission scanning electron microscopy. The MWCNTs/2D ZIF-L NSs nanocomposite was subsequently used to modify a screen-printed carbon electrode (SPCE) to achieve an electrochemical sensing platform for the detection of dacarbazine.</p><p><strong>Key results: </strong>From cyclic voltammetric studies, it was found that the MWCNTs/2D ZIF-L NSs nanocomposite modified SPCE provided less anodic peak potential (700 mV) and higher anodic peak current (7.7 μA) for oxidation of dacarbazine when compared to other SPCEs. The MWCNTs/2D ZIF-L NSs/SPCE displayed good performance in the quantitative determination of dacarbazine. Under optimum conditions, the differential pulse voltammetry response exhibited a linear concentration range of 0.01 to 80.0 μM for dacarbazine with a relatively high sensitivity of 0.1384 μA μM^-1 and an estimated detection limit of 0.004 μM. The MWCNTs/2D ZIF-L NSs/SPCE sensor was also successfully applied to the determination of dacarbazine in injections samples of dacarbazine.</p><p><strong>Conclusion: </strong>This detection method can be used as a valuable tool in the analysis of pharmaceutical formulations to bring benefits in cancer treatment.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 1","pages":"2617"},"PeriodicalIF":3.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of intraocular pressure and inflammation using febuxostat film: <i>in vitro</i> - <i>in vivo</i> correlation.","authors":"Mouli Das, Sk Habibullah, Tanisha Das, Rakesh Swain, Subrata Mallick","doi":"10.5599/admet.2601","DOIUrl":"https://doi.org/10.5599/admet.2601","url":null,"abstract":"<p><strong>Background and purpose: </strong>Urate crystal accumulation may lead to the condition of ocular tophaceous gout, causing ocular inflammation and increased intraocular pressure (IOP) due to the triggering of several inflammatory receptors like NLRP3, A2A, and TLR4. The study has been undertaken to manage intraocular pressure and inflammation using febuxostat (FBX) film formulation for sustained and improved activity, particularly for long-term tophaceous gout patients.</p><p><strong>Experimental approach: </strong>Hydroxypropyl methylcellulose K100 matrix-based hydrogel film of FBX has been fabricated in the presence of plasticizers like triethanolamine, dimethyl-sulphoxide (DMSO), or polyethylene glycol 600 using casting and evaporation technique. Carrageenan was injected into the upper palpebral region to induce ocular inflammation, and a normotensive rabbit eye model was used for monitoring IOP.</p><p><strong>Key results: </strong>Amorphization of the drug was observed from the differential scanning calorimetry and X-ray diffraction results. <i>In vitro</i> release study revealed an improved and diffusion-controlled sustained drug release for more than 5 h (62.69 to 84.76 %). Compared to its absence, decreased IOP was extended up to 5 h using film (with DMSO). Disappearance of ocular inflammation was also observed in the test animals after 2.5 h of film application, whereas acute inflammation was continued in the group without treatment for more than 4 h. Docking study revealed good binding interaction of drug and NLRP3, A2A, and TLR4 receptor.</p><p><strong>Conclusion: </strong>Febuxostat-loaded hydrogel-forming plasticized film could be utilized to better manage and control ocular inflammation and associated IOP, particularly in ocular tophaceous gout patients.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 2","pages":"2601"},"PeriodicalIF":3.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microwave coprocessing of modafinil with Gelucire^®: Thermal and compression characteristics.","authors":"Derar Omari, Assayed Sallam, Iyad Rashid, Shereen M Assaf, Faisal Al-Akayleh, Khaldoun A Al-Sou Od","doi":"10.5599/admet.2569","DOIUrl":"10.5599/admet.2569","url":null,"abstract":"<p><strong>Introduction: </strong>Modafinil, a wakefulness-promoting agent, is primarily used to treat excessive daytime sleepiness associated with narcolepsy and fatigue. As a BCS class II drug, modafinil exhibits low solubility and high permeability, with its crystalline structure significantly impacting dissolution, bioavailability, and compressibility. This study explores the use of microwave energy to alter the crystalline structure of modafinil in the presence of Gelucire^® 48/16, aiming to improve its pharmaceutical properties.</p><p><strong>Methods: </strong>Modafinil was treated with microwave energy to form complexes with Gelucire^® 48/16, and the resulting formulations were compared to hot-melt complexes and physical mixtures. The structural and thermal properties of the complexes were characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy. Compressibility and compactibility were evaluated through Kawakita model analysis and response surface methodology). The effect of microwaves on molecular interactions was further investigated using molecular modeling.</p><p><strong>Results: </strong>XRPD analysis revealed distinct crystalline patterns for microwave and hot-melt complexes compared to physical mixtures, with increased amorphousness observed through crystallinity, relative crystallinity, and relative intensity parameters. DSC thermograms indicated a reduction in melting endotherms and heat flow, suggesting structural changes due to complex formation. Compressibility and compactibility studies demonstrated optimal performance at low Gelucire^® content, with microwave-treated complexes exhibiting superior properties to untreated mixtures. Molecular modeling confirmed dipole-dipole interactions between modafinil and the hydrophilic portion of Gelucire^®.</p><p><strong>Conclusions: </strong>The study demonstrates that microwave energy effectively alters the crystalline structure of modafinil in the presence of Gelucire^® 48/16, enhancing its amorphousness, compressibility, and compatibility. These findings highlight the potential of microwave-assisted complexation as a novel approach to improve the pharmaceutical performance of BCS Class II drugs like modafinil.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 1","pages":"2569"},"PeriodicalIF":3.4,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of bicarbonate buffer on artificial membrane permeation of drugs.","authors":"Shiori Ishida, Samuel Lee, Balint Sinko, Karl Box, Kiyohiko Sugano","doi":"10.5599/admet.2603","DOIUrl":"10.5599/admet.2603","url":null,"abstract":"<p><strong>Background and purpose: </strong>The pH value of the small intestine is physiologically maintained by bicarbonate buffer (BCB). However, the effect of BCB on the membrane permeation of drugs has not been investigated. The purpose of this study was to investigate the effect of BCB on the passive membrane permeation of drugs.</p><p><strong>Experimental approach: </strong>The μFlux apparatus (pION Inc.) was used for permeability measurements. To avoid a pH change of BCB, a floating lid was newly developed for μFlux. The membrane filter was coated with a 10 % soybean lecithin-decane solution. The flux measurement was performed in an iso-pH condition (pH 6.5, BCB = 10 mM, buffer capacity (<i>β</i>)= 4.4 mM pH^-1). Phosphate buffer (PPB) with the same pH and <i>β</i> was used for comparison (PPB = 8 mM).</p><p><strong>Key results: </strong>The floating lid suppressed the pH increase to less than 0.1 for 120 min. The effective permeability (<i>P</i> _e) values of lipophilic weakly acidic and basic drugs were lower in BCB than in PPB (ketoprofen, naproxen, and propranolol). On the other hand, the <i>P</i> _e values in BCB and PPB were similar for unionizable drugs (caffeine and antipyrine) and hydrophilic weakly basic drugs (metoprolol and procainamide).</p><p><strong>Conclusion: </strong>Passive membrane permeation of lipophilic weakly acidic and basic drugs was slower in BCB than in PPB. This was suggested to be attributed to the slow neutralization rate of BCB, which affects the pH value adjacent to the membrane surface.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 1","pages":"2603"},"PeriodicalIF":3.4,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural polymer derivative-based pH-responsive nanoformulations with entrapped diketo-tautomers of 5-fluorouracil for enhanced cancer therapy.","authors":"Anbazhagan Thirumalai, Koyeli Girigoswami, Karthick Harini, Venkatakrishnan Kiran, Pazhani Durgadevi, Agnishwar Girigoswami","doi":"10.5599/admet.2554","DOIUrl":"10.5599/admet.2554","url":null,"abstract":"<p><strong>Background and purpose: </strong>Despite significant advancements in cancer therapies, chemotherapeutics continue to be the mainstay for treating cancer patients, with 5-fluorouracil (5-FU) being commonly used for various cancers. However, its limited ability to penetrate cell membranes and its short half-life, caused by rapid metabolism, necessitate frequent administration of high doses to maintain effective therapeutic levels. This study aimed to synthesize oxidized sodium alginate (OSA) derivatives to create OSA nanoparticles loaded with 5-FU (OSANP@ 5-FU), promoting diketo tautomers, and evaluate their photophysical properties, release profile, and anticancer activity with minimal toxicity.</p><p><strong>Experimental approach: </strong>The investigation encompassed physicochemical characterization, encapsulation efficiency, 5-FU release kinetics at pH 2.2 and 7.4, cell viability assessment via MTT assay in V79 cells, and in vitro anticancer efficacy in the A375 cell line.</p><p><strong>Key results: </strong>Steady-state absorption and emission confirmed the presence of advantageous diketone tautomers of 5-FU, indicating radiative transitions from the second singlet excited state to the ground state (S2→S0) and the drug's encapsulation within the polymeric nanostructure. Dynamic light scattering revealed that OSA nanoparticles, initially 177.8 nm, grew to 226.6 nm after encapsulating 5-FU, retaining high zeta potential for stability. With a 68% encapsulation efficiency, in vitro studies showed 46 to 54 % of 5-FU released across different pH levels within 510 minutes.</p><p><strong>Conclusion: </strong>In acidic conditions, there is a greater release of 5-FU than neutral pH levels, indicating a pH-responsive release profile beneficial for cancer treatment, with the release mechanism of OSANPs following Fickian diffusion as identified by a Korsmeyer-Peppas mathematical model and the formulation showing improved therapeutic efficacy.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 1","pages":"2554"},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flavonoids from <i>Clerodendrum</i> genus and their biological activities.","authors":"Meiske Naomi Mamuaja, Tati Herlina, Rymond Jusuf Rumampuk, Iman Permana Maksum, Yaya Rukayadi","doi":"10.5599/admet.2442","DOIUrl":"10.5599/admet.2442","url":null,"abstract":"<p><strong>Background and purpose: </strong>Many studies have been performed to identify new sources, their optimal isolation, and the biological activities of flavonoids due to nutraceutical, pharmaceutical, and cosmeceutical properties.</p><p><strong>Experimental approach: </strong>This review describes the method for flavonoid isolation and characteristic from the <i>Clerodendrum</i> genus and their biological activities with the indication of the most active ones. To perform a comprehensive review, a thorough literature review using Google Scholar, Scopus, and Science Direct was performed with keyword alone or in combination with other words.</p><p><strong>Key results: </strong>The isolation and identification of flavonoids from the Clerodendrum genus have revealed a variety of compounds using various methods. Various studies conducted <i>in vivo</i>, <i>in vitro</i> and <i>in silico</i> also reported bioactivities of these flavonoids.</p><p><strong>Conclusion: </strong>Several factors determine the flavonoid content in the <i>Clerodendrum</i> genus, among others, the different parts of the plant, extraction techniques, and solvent combination used. Isolated flavonoids also show significant biological activities, such as antioxidant, anti-inflammatory, antimicrobials, antidiabetic, anticancer, anti-tyrosinase, and neuroprotective agents.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"12 6","pages":"843-879"},"PeriodicalIF":3.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glyphosate-based herbicide metabolic profiles in human urine samples through proton nuclear magnetic resonance analysis.","authors":"Preechaya Tajai, Giatgong Konguthaithip, Thanyaphisit Chaikhaeng, Churdsak Jaikang","doi":"10.5599/admet.2476","DOIUrl":"10.5599/admet.2476","url":null,"abstract":"<p><strong>Background and purpose: </strong>Glyphosate-based herbicides, extensively utilized worldwide, raise concerns regarding potential human risks due to the detection of glyphosate (GLY) in human body fluids. This study aims to address critical knowledge gaps regarding whether GLY undergoes metabolism in humans, particularly considering the limited information available on human metabolism.</p><p><strong>Experimental approach: </strong>The study investigated GLY and its metabolites in eight amenity horticultural workers using proton nuclear magnetic resonance (¹H-NMR) data analysis. Multiple spot urine samples were collected before and after herbicide applications.</p><p><strong>Key results: </strong>Findings reveal the presence of GLY and its metabolites (AMPA, formaldehyde, sarcosine, glyoxylic acid, and methylamine). Results demonstrate a moderate correlation between median GLY concentration and its metabolites within the studied population.</p><p><strong>Conclusion: </strong>Persuasive evidence suggests the potential metabolism of GLY in humans. ¹H-NMR data analysis might be a promising technique for determining the metabolism of GLY in humans, offering valuable insights into urinary excretion patterns.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"12 6","pages":"957-970"},"PeriodicalIF":3.4,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural serine proteases and their applications in combating amyloid formation.","authors":"Sanjay Kisan Metkar, Saranya Udayakumar, Agnishwar Girigoswami, Koyeli Girigoswami","doi":"10.5599/admet.2551","DOIUrl":"10.5599/admet.2551","url":null,"abstract":"<p><strong>Background and purpose: </strong>Amyloidosis is a group of diseases including diabetes type II and neurological disorders, such as Alzheimer's disease, Parkinson's disease, prion disease, etc., where a common trait is observed; accumulation of misfolded protein at different parts of the body, especially the brain which manifests the typical symptoms like dementia, movement disorders, etc. These misfolded proteins, named amyloids, are protease resistant and thus it becomes difficult to manage these diseases in vivo. Enzymes that catalyse the complete breakdown of proteins are known as proteases. The peptide bonds in proteins are degraded by these serine proteases, which cause amyloid disaggregation.</p><p><strong>Experimental approach: </strong>We have searched for related articles using the search engines Google Scholar, PubMed, and Scopus for the past 10 years, selected the relevant articles, and written the outcomes and benefits of protease using the medical topic \"serine protease\" and the following text phrases -keratinase, lumbrokinase, serratiopeptidase, nattokinase.</p><p><strong>Key results: </strong>Alkaline serine proteases exhibit activity within the neutral to alkaline pH range. They are most capable of degrading host complement proteins, cytokines, and host clotting factors mostly due to their serine centre or metallotype. Because of its potential usage in food, pharmaceutical, and other industrial domains, this category of enzymes has been extensively investigated. Specifically, serine proteases are a group of enzymes that can be consumed orally and are stable in our gastrointestinal tract.</p><p><strong>Conclusion: </strong>In this review, we discussed the role of different serine proteases in amyloid aggregate inhibition and their potential application in treating amyloidosis.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"12 6","pages":"797-820"},"PeriodicalIF":3.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined approach of nanoemulgel and microneedle pre-treatment as a topical anticellulite therapy.","authors":"Hiba Imad Hameed, Mohammed Hussain Al-Mayahy","doi":"10.5599/admet.2461","DOIUrl":"10.5599/admet.2461","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cellulite is caused by changes in the metabolism of the fatty tissue beneath the skin. Methylxanthines and retinoids are commonly added to the different anticellulite products. However, their topical permeation into the dermis is limited. Thus, the objective of this research is to formulate a nanoemulgel (NEG) containing a triple therapy of caffeine, aminophylline, and tretinoin as a topical anticellulite product to improve their skin permeation. Furthermore, the influence of microneedles (MNs) as skin pre-treatment on the permeation of the NEG was investigated.</p><p><strong>Experimental approach: </strong>Various nanoemulsion (NE) formulations were prepared using high-energy ultrasonication with different compositions and sonication amplitudes. Several characterisation tests were employed to select the optimum NE formulation. Then, the optimised NE formulation was incorporated with hyaluronic acid to prepare the NEG, which was, in turn, subjected to various evaluations. An <i>ex vivo</i> permeation study using human skin was performed for the NEG compared to a control preparation of plain gel. Additionally, a microneedling pen was applied as a skin pre-treatment at varying lengths prior to NEG application to examine its impact on the NEG's permeation.</p><p><strong>Key results: </strong>The selected NEG has a homogenous and consistent texture with no coarse particles, a droplet size of 175.8 nm and polydispersity index (PDI) of 0.19, an optimum pH value of 5.28, high drug content of caffeine, aminophylline, and tretinoin (99.35, 98.48 and 98.05 %, respectively), high drug release values of approximately 100 % within 6 hours, appropriate viscosity, minimum skin irritation, and adequate short-term stability. The <i>ex vivo</i> permeation study showed that caffeine, aminophylline, and tretinoin permeated more and deposited in the skin with higher percentages from the NEG than plain gel. This skin deposition within the dermis was increased by applying the microneedling pen at varying lengths of 0.5, 1, and 2 mm as a skin pre-treatment.</p><p><strong>Conclusion: </strong>This combined approach of NEG formulation containing a triple therapy of caffeine, aminophylline, and tretinoin, along with MNs application, has the potential to serve as a topical anticellulite product, reducing cellulite formation and improving skin appearance.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"12 6","pages":"903-923"},"PeriodicalIF":3.4,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}