AAPS PharmSciTech最新文献

{"title":"Topical Foam for Simultaneous Treatment and Decontamination of Chemical Warfare Agents on Dermal Exposure.","authors":"Sonalika Arup Bhattaccharjee, Mohammad Shajid Ashraf Junaid, Meheli Ghosh, Ritesh Srivastava, Mohammad Athar, Ajay K Banga","doi":"10.1208/s12249-025-03177-6","DOIUrl":"https://doi.org/10.1208/s12249-025-03177-6","url":null,"abstract":"<p><p>Being highly toxic and a quick-acting vesicant, even small amounts of lewisite if not decontaminated immediately are rapidly absorbed into systemic circulation via skin exposure, leading to acute poisoning and death. The skin is the first major target to such chemical weapons. Although the stratum corneum provides a barrier lewisite being a lipophilic molecule that readily permeates this barrier. This necessitates, making early and thorough decontamination prior to manifestation of adverse effects. For this, we aimed to decontaminate skin using an antidote-loaded topical foam, followed by treating local and systemic toxicity using the same formulation. Successful incorporation of 1% antidote into a decontaminating topical foam and the delivery of 1.78 ± 0.21 µg/sq cm into dermatomed porcine ear skin within five minutes of application was achieved. Decontamination after five minutes of exposure (88.43%), as well as prolonged exposure (94.53%; 3 h) to methyl salicylate, a warfare chemical simulant, was demonstrated. The developed formulation demonstrated the potential to back-extract simulant from skin tissue but could not purge simulant penetrated systemic circulation. However, systemic delivery of the antidote was demonstrated, establishing the potential to treat the toxicity caused by the remnant warfare chemicals.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"178"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hot Melt Extruded Aceclofenac-Soluplus® Solid Dispersion: Mechanistic View of Miscibility and Drug-Carrier Interactions for Enhanced Dissolution.","authors":"Likhitha U, Roushan Bharti, Reema Narayan, Chetan H Mehta, Usha Yogendra Nayak","doi":"10.1208/s12249-025-03173-w","DOIUrl":"https://doi.org/10.1208/s12249-025-03173-w","url":null,"abstract":"<p><p>Aceclofenac (ACF), a Non-Steroidal Anti-Inflammatory Drug (NSAID), is formulated with Soluplus® (SOLP) to enhance solubility and bioavailability. This study presents a distinct approach by utilizing Hot Melt Extrusion (HME) to prepare Aceclofenac-Soluplus® solid dispersion (ACF-SOLP), in contrast to the previously investigated nanoemulsion technique. The HME technique facilitates a uniform drug distribution within the polymer matrix, increasing ACF's dissolution rate. Different weight ratios of ACF and SOLP were assessed with 1:8 (HM4), which proved to be the optimal choice. ACF is dispersed within SOLP in its amorphous state, and HM4 exhibited a significant increase in drug release as compared to pure ACF and its physical mixture. In vivo pharmacokinetic data of HM4 demonstrated a drastic improvement in the C_max (7.1 ± 0.14 µg/ml) and AUC (12.1 ± 1.30 µg-h/ml). Further, molecular dynamics simulation revealed that the polymer is widely dispersed within the supramolecular architecture of ACF-SOLP, with ACF positioned centrally, confirming the favorable interactions between the components. Leveraging the hydrophilic nature of the SOLP, the solid dispersion demonstrated enhanced dissolution of ACF, while HME synergistically reinforced the combination. This approach presents a compelling alternative to traditional methods, unlocking new possibilities for formulating poorly soluble drugs.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"180"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Delivery: Formulation Factors and Insights Into User Experience.","authors":"Shabbir Lobo, Zhangjie Xi, Debanjan Das, Norell M Hadzimichalis, John A Creek","doi":"10.1208/s12249-025-03171-y","DOIUrl":"https://doi.org/10.1208/s12249-025-03171-y","url":null,"abstract":"<p><p>Improving nasal spray use experience is typically not addressed as a key product requirement even though sensations of bitterness, sourness, astringency, or burning after intranasal application can cause significant repulsion, consumer non-compliance from recommended usage and product rejection. Extensive studies have been carried out by academia and industry alike into the formulation characteristics of sprays and consumer preferences to make nasal sprays more \"acceptable\" by patients. Due to lack of a collative synopsis of these works, this review article attempts to gather and summarize these studies, address the various attributes that impact post spray experience, and provide suggestions towards maximizing user compliance. We systematically categorized a range of factors which can contribute to unpleasant experiences using nasal sprays including anatomical characteristics of the nose, formulation and device properties, formulation components and dosages, etc. Furthermore, we collated relevant information from pharmaceutical and non-pharmaceutical domains to create a comprehensive knowledge base to frame the scope of the issue. Unpleasant sensorial attributes can be controlled by designing the formulation with a thorough understanding of product-device interactions and novel use of excipients. By choosing excipients such as taste masking agents, flavors, and novel polymers the behavior of the product in the nasal canal can be modulated to block the burning, astringent or bitterness sensation on spray use. This paper discusses these factors in comprehensive detail while offering solutions to ensure a superior product experience. The paper also discusses challenges to adoption and compliance strategies of some newer techniques and excipients.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"179"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Antimicrobial Nanofibers: Natural Integrations for Enhanced Wound Healing and Biofilm Disruption.","authors":"Eman Abdelhakeem, Heba Attia, Mona M Hashem, Mohamed A Abdel Khalek, Shaimaa M Badr-Eldin, Islam M Adel","doi":"10.1208/s12249-025-03178-5","DOIUrl":"https://doi.org/10.1208/s12249-025-03178-5","url":null,"abstract":"<p><p>Wound infections caused by multidrug-resistant bacteria present a substantial challenge in healthcare. Nanofibers, particularly when infused with natural extracts, are emerging as promising platforms for antimicrobial applications. This study investigates the potential of Anastatica hierochuntica extract-loaded electrospun nanofibers prepared with thermoplastic polyurethane for combating infections and promoting wound healing. Electrospinning was utilized to prepare nanofibers infused with Anastatica hierochuntica extract, resulting in uniform rod-shaped structures confirmed by scanning electron microscopy. The hydrophilicity of the nanofibers was assessed through water contact angle (WCA) measurements and swelling tests. Mechanical properties, including strain and stress were evaluated to determine suitability for drug delivery. The formulation with optimal properties, designated as NF20, underwent further investigation. Drug release profiles were analyzed over 72 h, and antimicrobial efficacy was tested against various pathogens, with comparisons made to Silymarin as a standard. A biofilm study evaluated the anti-virulence activity, while wound healing assays assessed the optimized extract loaded nanofibers potential in fostering tissue repair. The extract-loaded nanofibers exhibited enhanced hydrophilicity, with a WCA of 43.1 ± 0.6° and swelling of 216.67 ± 2.36% after 1 h. NF20 demonstrated superior mechanical properties, with strain and stress values of 67.6% and 0.0486 N/mm², respectively. The sustained release profile indicated 73.40 ± 1.31% release after 72 h. Antimicrobial tests revealed significant reductions in minimum inhibitory concentration, minimum bactericidal concentration, and minimum fungicidal concentration against key pathogens. The biofilm study confirmed extract loaded nanofiber's efficacy in inhibiting biofilm formation and disrupting established biofilms. These findings underscore the potential of the extract-loaded nanofiber composed of thermoplastic polyurethane as innovative wound dressings that enhance antimicrobial properties, promote accelerated healing and support tissue regeneration.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"181"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Delivery of Cetrorelix Via Lipid Liquid Crystal Nanoparticles: Characterization and Pharmacokinetic Studies in Rats.","authors":"Soheil Tafazzoli Mehrjardi, Mohsen Tafaghodi, Saba Malek, Davood Yari, Amir Hooshang Mohammadpour, Hossein Kamali, Ali Nokhodchi","doi":"10.1208/s12249-025-03169-6","DOIUrl":"https://doi.org/10.1208/s12249-025-03169-6","url":null,"abstract":"<p><p>Nasal sprays are extensively researched due to their rapid absorption, high bioavailability, and low side effects. Lipid liquid crystal nanoparticles (LLCNs) are being considered as potential carriers for intranasal delivery. LLCs loaded with cetrorelix (GnRH antagonist) were utilized for intranasal drug delivery to enhance brain targeting while minimizing systemic exposure. A single-phase formulation incorporating HPMC as a mucoadhesive was developed to extend nasal residence time. Following intranasal administration of cetrorelix in rats, its distribution in various brain regions and serum was assessed using LC-MS-MS. In the LLC formulation, the particle diameter, PDI, and Zeta potential were measured as 204.92 ± 0.89 nm, 0.188 ± 0.019, and -21.63 ± 1.72 mV, respectively. A monomodal distribution and low polydispersity index were observed, along with a negative zeta potential. Cetrorelix was released from the LLC in a biphasic profile, with an initial burst release of 30%, followed by a gradual and sustained release phase. The LLCs containing cetrorelix exhibited lower cytotoxicity compared to the LLC base. The nasal administration of cetrorelix via LLCs presents a promising advancement for nose-to-brain drug transport. The pharmacokinetic data demonstrated that the AUC_0-360min for brain tissue analysis, following nasal administration of the single-phase formulation, was 3.104 ng/ml.min. The value was 7.104 ng/ml.min for LLC nasal administration and 6.104 ng/ml.min for subcutaneous injection. The maximum concentration (C_max) values for brain tissue analysis indicated a significant increase with LLC nasal administration (238 ± 6. 2 ng/ml) in comparison to the single-phase formulation (202.5 ± 6.3 ng/ml) and subcutaneous injection (218.2 ± 3. 1 ng/ml). In serum analysis, the C_max values were significantly elevated, with subcutaneous injection achieving (4983.3 ± 2.5 ng/ml), followed by LLC nasal administration at (93.1 ± 6.2 ng/ml), and the single-phase formulation at (43.7 ± 2.2 ng/ml). This innovative method aims to target the brain directly, eliminating the need for needles, and reducing adverse effects, hence offering new hope for brain-targeted drug delivery. This study introduces, for the first time, a cetrorelix-loaded lipid liquid crystal (LLC) nanoparticle formulation for intranasal nose-to-brain delivery. The LLC system achieved enhanced brain targeting efficiency while reducing systemic exposure compared to conventional subcutaneous injections and simple nasal formulations, representing a promising advancement in GnRH drug delivery strategies.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"176"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in the Local Drug Delivery Systems for Diabetic Wound Healing: A Comprehensive Review.","authors":"Reem Khaled Wassif, Rehab Nabil Shamma, Nada M El-Hoffy, Maha El-Kayal","doi":"10.1208/s12249-025-03172-x","DOIUrl":"https://doi.org/10.1208/s12249-025-03172-x","url":null,"abstract":"<p><p>Wound management in diabetic patients holds significant importance in both clinical and social contexts due to the delayed and compromised healing that these individuals experience. Diabetic wounds exhibit slow and incomplete healing, increasing patients' susceptibility to infections. Managing wounds in diabetic patients, particularly when complicated by diabetic foot infection or diabetic foot ulcer, becomes challenging. The ideal drug delivery systems for treating diabetic wounds should integrate diverse drugs and/or biological factors, offering advantages such as sustained and localized release of therapeutic compounds and enhanced wound healing outcomes. Several treatment modalities are under investigation for managing diabetic wounds, including advanced local drug delivery systems such as topical 3D scaffolds, particulate systems, and 3D scaffolds combined with particulate systems, in addition to gas therapy and skin grafts as advanced therapies. This review comprehensively discusses the state of the art for each treatment modality for diabetic wound healing associated with bioactive molecules. It also summarizes the forms of topically applied 3D scaffolds, including films, hydrogels, sponges, nanofibers, wafers, microneedles, and foams. The review differentiates their advantages and disadvantages as topical therapies while discussing various scaffold types that integrate therapeutic agents, which include polymeric, inorganic, composite, and biological scaffolds. With the emphasis on the newly investigated locally administered drug delivery systems for the management of diabetic wounds, the review also focuses on the challenges and the future perspectives for the production of such systems with the use of various drugs and biomaterials using innovative technologies such as 3D printing for effective healing of wounds.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"177"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation Development and Characterization of Bigels Containing Curcumin for Topical Skin Delivery.","authors":"Lord Sam Liston, Suranate Phanapithakkun, Nuttakul Pimsarn, Nuttapon Dangkaokhia, Thanat Nakasan, Attawadee Sae Yoon, Hiroaki Todo, Teerapol Srichana, Somchai Sawatdee, Gerard Lee See, Florencio Arce, Pajaree Sakdiset","doi":"10.1208/s12249-025-03166-9","DOIUrl":"https://doi.org/10.1208/s12249-025-03166-9","url":null,"abstract":"<p><p>Curcumin, a pleiotropic molecule, has been reported to modulate skin health and functions owing to its anti-inflammation, wound healing, antimicrobial, and anti-aging effects. Curcumin, a lipophilic molecule, exhibits poor skin penetration that results in decreased efficacy in treating skin diseases. In this study, a bigel containing curcumin was formulated to enhance skin deposition of curcumin. Generally, bigels are composed of hydrogel (HG) and organogel (OG) and feature the ideal characteristics of both systems. The HG contained HPMC 2% w/v, and the OG contained Span® 60, almond oil, and curcumin (0.25%) mixed in different HG:OG proportions from 90:10 to 10:90. Three ratios of HG:OG, BG50 (50:50), BG40 (60:40), and BG30 (70:30) successfully formed yellowish turbid smooth bigels. The bigels were characterized as an o/w system with microdroplet size (7.10-30.60 µm) under a microscope. All bigel formulations showed pseudoplastic behavior and had low oil leaching. Skin permeation experiments revealed that BG30 provided the highest curcumin accumulation in the stratum corneum, and viable epidermis and dermis, which was higher than the control OG for 1.61 ± 0.17 and 3.63 ± 0.89-fold, respectively. All bigels were nontoxic on the murine fibroblast cell line L929 at 62.5-1,000 μg/mL of curcumin. B30 provided the highest wound healing effect as determined by the L929 scratch assay. The % migration increased to 70.11 ± 1.11 at 24 h and to 100% at 48 h. These findings suggest that BG30 could be potentially used to deliver curcumin intended for topical applications.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"175"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of Passion Fruit Oil Emulgel for Topical Chrysin Delivery and Ex Vivo Evaluation of Skin Permeation by Photoacoustic Spectroscopy.","authors":"Bruna Gheller de Souza, Lidiane Vizioli de Castro Hoshino, Thalita Schilive Faccin, Mauro Luciano Baesso, Fernanda Belincanta Borghi-Pangoni, Marcos Luciano Bruschi","doi":"10.1208/s12249-025-03164-x","DOIUrl":"https://doi.org/10.1208/s12249-025-03164-x","url":null,"abstract":"<p><p>Chrysin, a flavonoid effective against various skin cancers, displays poor solubility, skin permeation, and bioavailability. Emulgel emerges as an innovative and promising strategy for the topical administration of chrysin, offering significant advantages over existing systems. Passion fruit oil (PFO) enhances topical formulations with improved safety, compatibility, and drug delivery. However, current emulgels raise safety concerns due to their surfactant, co-surfactant, and oily co-solvent content. This study aimed to develop innovative emulgel containing PFO, without unsafe surfactants, for the topical delivery of chrysin. ATR-FTIR and DSC analyses of chrysin and excipients were performed. A 3³-factorial design was used, and the formulations were evaluated for preliminary physicochemical stability, mechanical and rheological properties, in-vitro release profile of chrysin, bioadhesion and ex-vivo skin permeation by photoacoustic spectroscopy (PAS). ATR-FTIR and DSC analyses confirmed the compatibility of chrysin with the formulation excipients. Formulations F6, F11, and F21 were stable and exhibited hardness (0.2006-0.4299 N), compressibility (1.4737-3.4300 N.mm), elasticity (0.9924 - 1.0034 mm), adhesiveness (0.8077-2.2217 N.mm), cohesiveness (0.7637 - 0.8733), softness index (0.0648 - 0.1525 N), and bioadhesive strength (0.0648 - 0.0754 N), both values with relative standard deviation less than 9%. They were pseudoplastic with yield value, thixotropy, and viscoelasticity. Chrysin release profile was slow and governed by anomalous transport. PAS analysis showed chrysin could permeate the stratum corneum and epidermis, reaching the dermal layer. The selected emulgels are promising for effective topical application, and the formulation F21 standing out in particular for further both in vitro and in vivo biological evaluations.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"173"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-delivery of Exemestane and Genistein via Chitosan Coated Liposomes for Enhanced Antitumor Effect and Bone Loss Prevention in Breast Cancer Therapy: In Vivo Evaluation.","authors":"Shwetakshi Sharma, S M Kawish, Priya Gupta, Shreshta Jain, Shahnawaz Ahmad, Zeenat Iqbal, Divya Vohora, Kanchan Kohli","doi":"10.1208/s12249-025-03163-y","DOIUrl":"https://doi.org/10.1208/s12249-025-03163-y","url":null,"abstract":"<p><p>Breast cancer (BC) is the most prevalent form of cancer among women worldwide, accounting for approximately 36% of cancer cases. Due to its inimitable pathological expression and restricted success of accessible therapeutic modalities, fanatical research in this area is essential. Our group has developed a nanovesicular lipid carrier system consisting of Exemestane (EXM) and Genistein (GNS), which have been successfully incorporated into both uncoated and chitosan-coated liposomes. This combination aims to enhance anticancer efficacy. EXM is known to cause bone loss, while GNS, a natural isoflavone, has been shown in research to possess bone-protective effects. Therefore, we combined these two compounds to mitigate the side effects of EXM. Our previous publication details the formulation development of uncoated EXM-GNS liposomes (EXM-GNS-LPS) and chitosan-coated EXM-GNS liposomes (CH-EXM-GNS-LPS), where we addressed the pharmacotechnical challenges of combining a synthetic drug with herbal drug. Both uncoated and coated liposomes were tested for their budding effects on bone loss induced by hormonal therapy. Pharmacokinetic and pharmacodynamic studies were conducted on rat models with breast cancer, treated with different formulations. Biochemical investigations revealed significant changes in biomarker levels, indicating effects on bone development and resorption. Improvements in bone health and anticancer efficacy were observed to be statistically significant (p < 0.05). Micro-CT analysis of bone samples showed that the chitosan-coated EXM-GNS liposome treatment group yielded the best results when evaluate against other treatment groups. Additionally, histological examination of the bone treated with CH-EXM-GNS-LPS demonstrated a marked restoration of trabecular bone architecture, characterized by a well-connected bone matrix and narrower inter-trabecular spaces compared to the toxic control group. The synergistic effect of EXM and GNS, encapsulated in liposomes, offers an innovative solution to the challenges of breast cancer treatment. The chitosan coating not only improved the stability and controlled release of the drugs but also provided additional benefits in terms of biocompatibility and targeting potential. Overall, the results of this study indicate that the CH-EXM-GNS-LPS formulation holds significant promise as a therapeutic and preventive strategy for bone loss associated with hormonal therapy in breast cancer patients. This work lays the foundation for future clinical applications, highlighting the potential for combining synthetic and natural compounds in advanced drug delivery systems to address complex, multifactorial health issues.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"174"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phospholipid Complex-based Topical Gel for Codelivery of Erlotinib and Methotrexate in Psoriasis.","authors":"Sanyog Jain, Shivani Mali, Junia Akhtar, Chander Parkash Dora, Rahul R Mahajan","doi":"10.1208/s12249-025-03168-7","DOIUrl":"https://doi.org/10.1208/s12249-025-03168-7","url":null,"abstract":"<p><p>Topical drug delivery systems offer a targeted and patient-compliant approach for managing psoriasis, enabling noninvasive, localized, and sustained therapy, with reduced systemic side effects and improved therapeutic outcomes. In this study, we prepared phospholipid complex (PLC) based gel of methotrexate (MTX) and erlotinib (ERL) as a potential dual treatment for psoriasis. The phospholipids used in this study were biocompatible and exhibited enhanced skin permeation. The physical interactions between drugs and phospholipids in the MTX-loaded phospholipid complex (MPLC) and ERL-loaded phospholipid complex (EPLC) were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (¹H NMR), and powder X-ray diffraction (P-XRD). Scanning electron microscopy (SEM) confirmed amorphization of the drug upon complexation, and transmission electron microscopy (TEM) indicated that the complexes formed a spherical morphology. Furthermore, gel-embedded drug-phospholipid complexes exhibited slower diffusion-based sustained release profiles, with ~ 40% release of ERL from EPLC and ~ 60% release of MTX from MPLC over 24 h, in contrast to the faster release of ~ 65% and ~ 90% observed for free ERL and MTX, respectively. Skin permeation studies (Franz diffusion cells), dermal pharmacokinetics studies, and in vivo antipsoriatic activity studies (imiquimod (IMQ)-induced psoriasis model) were performed to evaluate the efficacy of the optimized formulation. This first-in-class combination therapy provides better lesion control and reduced inflammation while minimizing systemic adverse effects, highlighting the potential of drug-phospholipid complexes for targeted, sustained delivery in psoriasis treatment.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"172"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}