Preparation and Application of Decanoic Acid/Arginine Hydrogels to a Transdermal Formulation.

We prepared a supramolecular hydrogel composed of decanoic acid and arginine (C10/Arg gel) and evaluated its application to a transdermal formulation. C10/Arg gel adjusted to pH 7 with 1 M NaOH aq or 1 M HCl aq provided a translucent hydrogel with a lamellar liquid crystal structure in the concentration region of decanoic acid ≥12% and arginine ≤9%. Rheological measurements showed that C10/Arg gel is a viscoelastic material with both solid and liquid properties, with elasticity being dominant over viscosity in the low shear stress region. The skin permeability of hydrocortisone (HC) and indomethacin (IM) from C10/Arg gels was investigated in vitro using hairless mouse skin and compared to control formulation drug suspensions (IM or HC) in water. The cumulative permeation amount of HC and IM from the C10/Arg gel at 10 h after application was approximately 16 and 11 times higher than that of the control, respectively. On the other hand, the flux of IM decreased with increasing arginine concentration, likely due to the acid-base interaction between Arg and IM in C10/Arg gel. Adequate drug skin permeation enhancement by C10/Arg gel requires optimizing the gel composition for each specific drug.

Lipid-based microemulsion gel for the topical delivery of methotrexate: an optimized, rheologically acceptable formulation with conducive dermatokinetics.

In the present study, we have formulated a methotrexate (MTX)-loaded microemulsion topical gel employing quality-by-design optimization. The optimized lipid-based microemulsion was incorporated into a 2% carbopol gel. The prepared formulation was characterized for micromeritics, surface charge, surface morphology, conductivity studies, rheology studies, texture analysis/spreadability, drug entrapment, and drug loading studies. The formulation was further evaluated for drug release and release kinetics, cytotoxicity assays, drug permeation and drug retention studies, and dermatokinetics. The developed nanosystem was not only rheologically acceptable but also offered substantial drug entrapment and loading. From drug release studies, it was observed that the nanogel showed higher drug release at pH 5.0 compared to plain MTX, plain gel, and plain microemulsion. The developed system with improved dermatokinetics, nanometric size, higher drug loading, and enhanced efficacy towards A314 squamous epithelial cells offers a huge promise in the topical delivery of methotrexate.

Formulation development of tazarotene-loaded PLGA nanoparticles for follicular delivery in the treatment of inflammatory skin diseases.

Tazarotene is a widely prescribed topical retinoid for acne vulgaris and plaque psoriasis and is associated with skin irritation, dryness, flaking, and photosensitivity. In vitro permeation of tazarotene was studied across the dermatomed human and full-thickness porcine skin. The conversion of tazarotene to the active form tazarotenic acid was studied in various skin models. Tazarotene-loaded PLGA nanoparticles were prepared using the nanoprecipitation technique to target skin and hair follicles effectively. The effect of formulation and processing variables on nanoparticle properties, such as particle size and drug loading, was investigated. The optimized nanoparticle batches with particle size <500 µm were characterized further for FT-IR analysis, which indicated no interactions between tazarotene and PLGA. Scanning electron microscopy analysis showed uniform, spherical, and non-agglomerated nanoparticles. In vitro release study using a dialysis membrane indicated a sustained release of 40-70 % for different batches over 36 h, following a diffusion-based release mechanism based on the Higuchi model. In vitro permeation testing (IVPT) in full-thickness porcine skin showed significantly enhanced follicular and skin delivery from nanoparticles compared to solution. The presence of tazarotenic acid in the skin from tazarotene nanoparticles indicated the effectiveness of nanoparticle formulations in retaining bioconversion ability and targeting follicular delivery.

Laser-mediated Solutions: Breaking Barriers in Transdermal Drug Delivery.

Skin diseases pose challenges in treatment due to the skin's complex structure and protective functions. Topical drug delivery has emerged as a preferred method for treating these conditions, offering localized therapy with minimal systemic side effects. However, the skin's barrier properties frequently limit topical treatments' efficacy by preventing drug penetration into deeper skin layers. In recent years, laser-assisted drug delivery (LADD) has gained attention as a promising strategy to overcome these limitations. LADD involves using lasers to create microchannels in the skin, facilitating the deposition of drugs and enhancing their penetration into the target tissue. Several lasers, such as fractional CO2, have been tested to see how well they work at delivering drugs. Despite the promising outcomes demonstrated in preclinical and clinical studies, several challenges persist in implementing LADD, including limited penetration depth, potential tissue damage, and the cost of LADD systems. Furthermore, selecting appropriate laser parameters and drug formulations is crucial to ensuring optimal therapeutic outcomes. Nevertheless, LADD holds significant potential for improving treatment efficacy for various skin conditions, including skin cancers, scars, and dermatological disorders. Future research efforts should focus on optimizing LADD techniques, addressing safety concerns, and exploring novel drug formulations to maximize the therapeutic benefits of this innovative approach. With continued advancements in laser technology and pharmaceutical science, LADD has the potential to revolutionize the field of dermatology and enhance patient care.

Navigating Skin Delivery Horizon: An Innovative Approach in Pioneering Surface Modification of Ultradeformable Vesicles.

In the dynamic landscape of pharmaceutical advancements, the strategic application of active pharmaceutical ingredients to the skin through topical and transdermal routes has emerged as a compelling avenue for therapeutic interventions. This non-invasive approach has garnered considerable attention in recent decades, with numerous attempts yielding approaches and demonstrating substantial clinical potential. However, the formidable barrier function of the skin, mainly the confinement of drugs on the upper layers of the stratum corneum, poses a substantial hurdle, impeding successful drug delivery via this route. Ultradeformable vesicles/carriers (UDVs), positioned within the expansive realm of nanomedicine, have emerged as a promising tool for developing advanced dermal and transdermal therapies. The current review focuses on improving the passive dermal and transdermal targeting capacity by integrating functionalization groups by strategic surface modification of drug-loaded UDV nanocarriers. The present review discusses the details of case studies of different surface-modified UDVs with their bonding strategies and covers the recent patents and clinical trials. The design of surface modifications holds promise for overcoming existing challenges in drug delivery by marking a significant leap forward in the field of pharmaceutical sciences.

Naringenin-Zinc Oxide Nanocomposites Amalgamated Polymeric Gel Augmented Drug Delivery and Attenuated Experimental Cutaneous Candidiasis in Balb/c Mice: In Vitro and In Vivo Studies.

Naringenin (NRG) inhibits the fungal 17ß-hydroxysteroid dehydrogenase accountable for ergosterol synthesis in Candida albicans (C. albicans), a causative agent for cutaneous candidiasis. In present research, NRG was complexed with ZnO nanomaterial (NRG-Zn2+) to synthesize NRG-Zn2+ nanocomposites. The particle size and ζ-potential of NRG-Zn2+ nanocomposites were respectively estimated to be 180.33 ± 1.22-nm and - 3.92 ± 0.35-mV. In silico data predicted the greater affinity of NRG-Zn2+ nanocomposite for 14α-demethylase and ceramide in comparison to NRG alone. Later, NRG-Zn2+ nanocomposites solution was transformed in to naringenin-zinc oxide nanocomposites loaded chitosan gel (NRG-Zn-CS-Gel) with viscosity and firmness of 854806.7 ± 52386.43 cP and 698.27 ± 10.35 g, respectively. The ex-vivo skin permeation demonstrated 70.49 ± 5.22% skin retention, significantly greater (P < 0.05) than 44.48 ± 3.06% of naringenin loaded chitosan gel (NRG-CS-Gel) and 31.24 ± 3.28% of naringenin solution (NRG Solution). NRG-Zn-CS-Gel demonstrated 6.71 ± 0.84% permeation of NRG with a flux value of 0.046 ± 0.01-µg/cm2/h. The MIC50 of NRG-Zn-CS-Gel against C. albicans was estimated to be 0.156-µg/mL with FICI (fractional inhibitory concentration index) of 0.018 that consequently exhibited synergistic efficacy. Further, NRG-Zn-CS-Gel demonstrated superior antifungal efficacy in C. albicans induced cutaneous candidiasis infection in Balb/c mice. The fungal burden in NRG-Zn-CS-Gel treated group was 109 ± 25 CFU/mL, significantly lower (P < 0.05) than positive control (2260 ± 446 CFU/mL), naringenin loaded chitosan gel (NRG-CS-Gel; 928 ± 127 CFU/mL) and chitosan gel (CS-Gel; 2116 ± 186 CFU/mL) treated mice. Further, histopathology examination and cytokine profiling of TNF-α, IL-1ß and IL-10 revealed the healing of skin and inflammation associated with cutaneous candidiasis infection. In conclusion, NRG-Zn-CS-Gel may be a potential candidate for translating in to a clinical viable topical nanotherapeutic.

In vitro evaluation of the percutaneous absorption of progesterone in anhydrous permeation-enhancing base using the Franz skin finite dose model and mass spectrometry.

Progesterone is used for hormone replacement therapy through various routes of administration. This study was conducted to (a) evaluate the stability of progesterone in a proprietary anhydrous permeation-enhancing base (APEB) and the efficiency of its skin permeation, and (b) determine the appropriateness of mass spectrometry as a method of analysis for permeated progesterone. Using a proven stability-indicating ultra-performance liquid chromatographic method, the compounded hormone (100 mg progesterone/g APEB gel) was determined to be physically and chemically stable at room temperature for six months. Skin permeation analysis using the Franz skin finite dose model and mass spectrometry imaging showed an optical density of 1699 for the permeated progesterone compounded in APEB and 550 for the permeated progesterone in a water containing VBC, which is a statistically significant different (P = 0.029). The study suggests that APEB can be used as a compounding base for effective skin permeation of progesterone, and mass spectrometry is a reliable method for visualization and quantitative analysis of permeated progesterone.

Calcipotriol Nanosuspension-Loaded Trilayer Dissolving Microneedle Patches for the Treatment of Psoriasis: In Vitro Delivery and In Vivo Antipsoriatic Activity Studies.

Psoriasis, affecting 2-3% of the global population, is a chronic inflammatory skin condition without a definitive cure. Current treatments focus on managing symptoms. Recognizing the need for innovative drug delivery methods to enhance patient adherence, this study explores a new approach using calcipotriol monohydrate (CPM), a primary topical treatment for psoriasis. Despite its effectiveness, CPM's therapeutic potential is often limited by factors like the greasiness of topical applications, poor skin permeability, low skin retention, and lack of controlled delivery. To overcome these challenges, the study introduces CPM in the form of nanosuspensions (NSs), characterized by an average particle size of 211 ± 2 nm. These CPM NSs are then incorporated into a trilayer dissolving microneedle patch (MAP) made from poly(vinylpyrrolidone) and w poly(vinyl alcohol) as needle arrays and prefrom 3D printed polylactic acid backing layer. This MAP features rapidly dissolving tips and exhibits good mechanical properties and insertion capability with delivery efficiency compared to the conventional Daivonex ointment. The effectiveness of this novel MAP was tested on Sprague-Dawley rats with imiquimod-induced psoriasis, demonstrating efficacy comparable to the marketed ointment. This innovative trilayer dissolving MAP represents a promising new local delivery system for calcipotriol, potentially revolutionizing psoriasis treatment by enhancing drug delivery and patient compliance.

Novel extended-release transdermal formulations of the psychedelic N,N-dimethyltryptamine (DMT).

There is considerable evidence from the literature that psychedelics, such as N,N-dimethyltryptamine (DMT), are safe and effective treatments for depression. However, clinical administration to induce psychedelic effects and expensive psychotherapy-assisted treatments likely limit accessibility to the average patient. There is emerging evidence that DMT promotes positive behavioral changes in vivo at sub-hallucinogenic dosages, and depending on the target indication, subjecting patients to high, bolus dosages may not be necessary. Due to rapid metabolic degradation, achieving target levels of DMT in subjects is difficult, requiring IV administration, which poses risks to patients during the intense hallucinogenic and subjective drug effects. The chemical and physical properties of DMT make it an excellent candidate for non-invasive, transdermal delivery platforms. This paper outlines the formulation development, in vitro, and in vivo testing of transdermal drug-in-adhesive DMT patches using various adhesives and permeation enhancers. In vivo behavioral and pharmacokinetic studies were performed with lead patch formulation (F5) in male and female Swiss Webster mice, and resulting DMT levels in plasma and brain samples were quantified using LC/MS/MS. Notable differences were seen in female versus male mice during IV administration; however, transdermal administration provided consistent, extended drug release at a non-hallucinogenic dose. The IV half-life of DMT was extended by 20-fold with administration of the transdermal delivery system at sub-hallucinogenic plasma concentrations not exceeding 60 ng/mL. Results of a translational head twitch assay (a surrogate for hallucinogenic effects in non-human organisms) were consistent with absence of hallucinations at low plasma levels achieved with our TDDS. Despite the reported low bioavailability of DMT, the non-invasive transdermal DMT patch F5 afforded an impressive 77 % bioavailability compared to IV at two dosages. This unique transdermal delivery option has the potential to provide an out-patient treatment option for ailments not requiring higher, bolus doses and is especially intriguing for therapeutic indications requiring non-hallucinogenic alternatives.

Solubilization mechanism of α-glycosylated naringin based on self-assembled nanostructures and its application to skin formulation.

We previously reported that α-glycosylated naringin (naringin-G), synthesized by enzyme-catalyzed transglycosylation, can enhance the solubility of poorly water-soluble compounds without surface-active property. However, the solubilization mechanism has not been fully elucidated. In this study, the solubilization mechanism of naringin-G was investigated using nuclear magnetic resonance (NMR) spectroscopy, and its application in skin formulations was further investigated. 1H NMR and dynamic light scattering measurements at various concentrations confirmed the self-assembled nanostructures of naringin-G above a critical aggregation concentration of approximately 2.2 mg/mL. Two-dimensional 1H-1H nuclear Overhauser effect spectroscopy and solubility tests revealed that flavone with poor water solubility, could be solubilized in its self-assembled structure with a stoichiometric relationship with naringin-G. When naringin-G was included in the skin formulation, the permeated amount and permeability coefficient (Papp) of flavones improved up to four times with increasing amounts of naringin-G. However, flavone solubilization by adding an excessive amount of naringin-G resulted in a decreased permeated amount and Papp of flavones, indicating the interplay between the apparent solubility and skin permeability of flavones. Naringin-G, which forms a nanoaggregate structure without exhibiting surface-active properties, has the potential to enhance the solubility and skin permeation of poorly water-soluble compounds.

Development of a film-forming oleogel with increased substantivity for the treatment of psoriasis.

The aim of this work was the development of a film-forming formulation (FFF) for the topical treatment of psoriasis that shows an increased substantivity compared to conventional semi-solid dosage forms. The developed formulation is an oleogel. It is based on a combination of castor oil and medium chain triglycerides, and the oil-soluble film former MP-30 (Croda GmbH, Nettetal, Germany), a polyamide that upon mixing with a polar oil entraps the oil und thus substantially increases the viscosity of the formulation up to a semisolid state. Betamethasone dipropionate (BDP) and calcipotriole (CA) were used as active pharmaceutical ingredients (APIs). Oleogels of different compositions were evaluated regarding substantivity, rheological properties, ex-vivo penetration into the skin and ex-vivo permeation through the skin. Marketed products were used as controls. It was found that the amount of betamethasone dipropionate penetrating and permeating into and through the skin from the film-forming formulation is at an intermediate value compared to the marketed products. The substantivity of the developed formulation is described by an amount of 57.7 % formulation that remains on the skin surface and is thus significantly higher compared to the marketed products. In the film forming formulation, the proportion of API penetrating the skin remains the same when the skin repetitively brought in contact with a piece of textile during the penetration experiment. In contrast with the in-market formulations tested, this proportion was reduced by up to 97 %. As a result, the developed formulations can lead to an increased patient compliance.

Low drug load, high retention mometasone furoate cream with polyglyceryl - 3 oleate as a chemical enhancer: Formulation development, in vivo and in vitro evaluation and molecular mechanisms.

The study aimed to create a low loading, high retention, easier to apply O/W mometasone furoate (MF) cream using a chemical enhancer (CE) approach to provide more options for patients with atopic dermatitis (AD) and to investigate molecular mechanisms of its increased release and retention. A Box-Behnken design determined the optimal formulation based on stability and in vitro skin retention. Evaluations included appearance, rheological properties, irritation, in vivo tissue distribution and pharmacodynamics. Molecular mechanisms of enhanced release were studied using high-speed centrifugation, molecular dynamics and rheology. The interaction between the CE, MF and skin was studied by tape stripping, CLSM, ATR-FTIR and SAXS. The formulation was optimized to contain 0.05% MF and used 10% polyglyceryl-3 oleate (POCC) as the CE. There was no significant difference from Elocon® cream in in vivo retention and pharmacodynamics but increased in vivo retention by 3.14-fold and in vitro release by 1.77-fold compared to the basic formulation. POCC reduced oil phase cohesive energy density, enhancing drug mobility and release. It disrupted skin lipid phases, aiding drug entry and formed hydrogen bonds, prolonging retention. This study highlights POCC as a CE in the cream, offering insights for semi-solid formulation development.

Novel nano-in-micro fabrication technique of diclofenac nanoparticles loaded microneedle patches for localised and systemic drug delivery.

Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly prescribed for managing osteoarthritis, rheumatoid arthritis, and post-surgical pain. However, oral administration of diclofenac often leads to adverse effects. This study introduces an innovative nano-in-micro approach to create diclofenac nanoparticle-loaded microneedle patches aimed at localised, sustained pain relief, circumventing the drawbacks of oral delivery. The nanoparticles were produced via wet-milling, achieving an average size of 200 nm, and then incorporated into microneedle patches. These patches showed improved skin penetration in ex vivo tests using Franz-cell setups compared to traditional diclofenac formulations. In vivo tests on rats revealed that the nanoparticle-loaded microneedle patches allowed for quick drug uptake and prolonged release, maintaining drug levels in tissues for up to 72 h. With a systemic bioavailability of 57 %, these patches prove to be an effective means of transdermal drug delivery. This study highlights the potential of this novel microneedle delivery system in enhancing the treatment of chronic pain with reduced systemic side effects.

Nanosuspension-Loaded Dissolving Microneedle Patches for Enhanced Transdermal Delivery of a Highly Lipophilic Cannabidiol.

Purpose: Transdermal Drug Delivery System (TDDS) offers a promising alternative for delivering poorly soluble drugs, challenged by the stratum corneum's barrier effect, which restricts the pool of drug candidates suitable for TDDS. This study aims to establish a delivery platform specifically for highly lipophilic drugs requiring high doses (log P > 5, dose > 10 mg/kg/d), to improve their intradermal delivery and enhance solubility. Methods: Cannabidiol (CBD, log P = 5.91) served as the model drug. A CBD nanosuspension (CBD-NS) was prepared using a bottom-up method. The particle size, polydispersity index (PDI), zeta potential, and concentration of the CBD-NS were characterized. Subsequently, CBD-NS was incorporated into dissolving microneedles (DMNs) through a one-step manufacturing process. The intradermal dissolution abilities, physicochemical properties, mechanical strength, insertion depth, and release behavior of the DMNs were evaluated. Sprague-Dawley (SD) rats were utilized to assess the efficacy of the DMN patch in treating knee synovitis and to analyze its skin permeation kinetics and pharmacokinetic performance. Results: The CBD-NS, stabilized with Tween 80, exhibited a particle size of 166.83 ± 3.33 nm, a PDI of 0.21 ± 0.07, and a concentration of 46.11 ± 0.52 mg/mL. The DMN loaded with CBD-NS demonstrated favorable intradermal dissolution and mechanical properties. It effectively increased the delivery of CBD into the skin, extended the action's duration in vivo, and enhanced bioavailability. CBD-NS DMN exhibited superior therapeutic efficacy and safety in a rat model of knee synovitis, significantly inhibiting TNF-α and IL-1ß compared with the methotrexate subcutaneous injection method. Conclusion: NS technology effectively enhances the solubility of the poorly soluble drug CBD, while DMN facilitates penetration, extends the duration of action in vivo, and improves bioavailability. Furthermore, CBD has shown promising therapeutic outcomes in treating knee synovitis. This innovative drug delivery system is expected to offer a more efficient solution for the administration of highly lipophilic drugs akin to CBD, thereby facilitating high-dose administration.

Formulation and evaluation of miconazole lipogel for enhanced drug permeation.

Hydrophilic drugs could be incorporated into the skin surface by manes of Lipogel. This study aimed to prepare miconazole lipogel with natural ingredients to enhance drug permeability using dimethyl Sulfoxide (DMSO). The miconazole lipogels, A1 (without DMSO) and A2 (with DMSO) were formulated and evaluated for organoleptic evaluation, pH, viscosity, stability studies, freeze-thawing, drug release profile and drug permeation enhancement. Results had stated that prepared lipogel's pH falls within the acceptable range required for topical delivery (4 to 6) while both formulations show good results in organoleptic evaluation. The A2 formulation containing DMSO shows better permeation of miconazole (84.76%) on the artificial skin membrane as compared to A1 lipogel formulation (50.64%). In in-vitro drug release studies, A2 for-mulation showed 87.48% drug release while A1 showed just 60.1% drug release from lipogel. Stability studies were performed on model formulations under environmental conditions and both showed good spreadibility, stable pH, free of grittiness and good consistency in formulation. The results concluded that A2 formulation containing DMSO shows better results as compared to DMSO-free drug lipogel.

A bio-ionic liquid based self-healable and adhesive ionic hydrogel for the on-demand transdermal delivery of a chemotherapeutic drug.

The non-invasive nature and potential for sustained release make transdermal drug administration an appealing treatment option for cancer therapy. However, the strong barrier of the stratum corneum (SC) poses a challenge for the penetration of hydrophilic chemotherapy drugs such as 5-fluorouracil (5-FU). Due to its biocompatibility and capacity to increase drug solubility and permeability, especially when paired with chemical enhancers, such as oleic acid (OA), which is used in this work, choline glycinate ([Cho][Gly]) has emerged as a potential substance for transdermal drug delivery. In this work, we examined the possibility of transdermal delivery of 5-FU for the treatment of breast cancer using an ionic hydrogel formulation consisting of [Cho][Gly] with OA. Small angle neutron scattering, rheological analysis, field emission scanning electron microscopy, and dynamic light scattering analysis were used to characterize the ionic hydrogel. The non-covalent interactions present between [Cho][Gly] and OA were investigated by computational simulations and FTIR spectroscopy methods. When subjected to in vitro drug permeation using goat skin in a Franz diffusion cell, the hydrogel demonstrated sustained release of 5-FU and effective permeability in the order: [Cho][Gly]-OA gel > [Cho][Gly] > PBS (control). The hydrogel also demonstrated 92% cell viability after 48 hours for the human keratinocyte cell line (HaCaT cells) as well as the normal human cell line L-132. The breast cancer cell line MCF-7 and the cervical cancer cell line HeLa were used to study in vitro cytotoxicity that was considerably affected by the 5-FU-loaded hydrogel. These results indicate the potential of the hydrogel as a transdermal drug delivery vehicle for the treatment of breast cancer.

Influence of Surfactant on the Skin Permeation of Methylisothiazolinone and Methylchloroisothiazolinone.

Patch tests are often used in safety evaluations to identify the substance causing skin irritation, but the same substance can sometimes give positive or negative results depending on the test conditions. Here, we investigated differences in the skin penetration of two test compounds under different application conditions. We studied the effects of the anionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant polysorbate 80 (PS) on skin penetration of the preservatives methylisothiazolinone (MT) and methylchloroisothiazolinone (MCT), which are used in cosmetics such as shampoos. The skin permeation of MT was enhanced by SDS but was unchanged by PS. Skin impedance decreased in the presence of SDS whereas PS had the same effect as the control aqueous solution, suggesting that SDS reduction of the barrier function of skin affects the permeation of MT, a hydrophilic drug. Application of a mixture of MCT and MT in the presence of SDS did not affect the skin permeation of MCT whereas the permeation of MT was enhanced by SDS, indicating that the skin permeation of MCT is less affected by SDS than is MT. Thus, attention should be paid to the possible effect of co-solutes, especially hydrophilic drugs.

Transdermal Delivery of Niacin Through Polysaccharide Films Ameliorates Cutaneous Flushing in Experimental Wistar Rats.

BACKGROUND: Niacin, an established therapeutic for dyslipidemia, is hindered by its propensity to induce significant cutaneous flushing when administered orally in its unmodified state, thereby constraining its clinical utility. OBJECTIVE: This study aimed to fabricate, characterize, and assess the in-vitro and in-vivo effectiveness of niacin-loaded polymeric films (NLPFs) comprised of carboxymethyl tamarind seed polysaccharide. The primary objective was to mitigate the flushing-related side effects associated with oral niacin administration. METHODS: NLPFs were synthesized using the solvent casting method and subsequently subjected to characterization, including assessments of tensile strength, moisture uptake, thickness, and folding endurance. Surface characteristics were analyzed using a surface profiler and scanning electron microscopy (SEM). Potential interactions between niacin and the polysaccharide core were investigated through X-ray diffraction experiments (XRD) and Fourier transform infrared spectroscopy (FTIR). The viscoelastic properties of the films were explored using a Rheometer. In-vitro assessments included drug release studies, swelling behavior assays, and antioxidant assays. In-vivo efficacy was evaluated through skin permeation assays, skin irritation assays, and histopathological analyses. RESULTS: NLPFs exhibited a smooth texture with favorable tensile strength and moisture absorption capabilities. Niacin demonstrated interaction with the polysaccharide core, rendering the films amorphous. The films displayed slow and sustained drug release, exceptional antioxidant properties, optimal swelling behavior, and viscoelastic characteristics. Furthermore, the films exhibited biocompatibility and non-toxicity towards skin cells. CONCLUSION: NLPFs emerged as promising carrier systems for the therapeutic transdermal delivery of niacin, effectively mitigating its flushing-associated adverse effects.

Organogels: "GelVolution" in Topical Drug Delivery - Present and Beyond.

Topical drug delivery holds immense significance in dermatological treatments due to its non-invasive nature and direct application to the target site. Organogels, a promising class of topical drug delivery systems, have acquired substantial attention for enhancing drug delivery efficiency. This review article aims to explore the advantages of organogels, including enhanced drug solubility, controlled release, improved skin penetration, non-greasy formulations, and ease of application. The mechanism of organogel permeation into the skin is discussed, along with formulation strategies, which encompass the selection of gelling agents, cogelling agents, and additives while considering the influence of temperature and pH on gel formation. Various types of organogelators and organogels and their properties, such as viscoelasticity, non-birefringence, thermal stability, and optical clarity, are presented. Moreover, the biomedical applications of organogels in targeting skin cancer, anti-inflammatory drug delivery, and antifungal drug delivery are discussed. Characterization parameters, biocompatibility, safety considerations, and future directions in optimizing skin permeation, ensuring long-term stability, addressing regulatory challenges, and exploring potential combination therapies are thoroughly examined. Overall, this review highlights the immense potential of organogels in redefining topical drug delivery and their significant impact on the field of dermatological treatments, thus paving the way for exciting prospects in the domain.

Key Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in vivo.

Purpose: Cannabidiol (CBD) is a promising therapeutic drug with low addictive potential and a favorable safety profile. However, CBD did face certain challenges, including poor solubility in water and low oral bioavailability. To harness the potential of CBD by combining it with a transdermal drug delivery system (TDDS). This innovative approach sought to develop a transdermal patch dosage form with micellar vesicular nanocarriers to enhance the bioavailability of CBD, leading to improved therapeutic outcomes. Methods: A skin-penetrating micellar vesicular nanocarriers, prepared using nano emulsion method, cannabidiol loaded transdermal nanocarriers-12 (CTD-12) was presented with a small particle size, high encapsulation efficiency, and a drug-loaded ratio for CBD. The skin permeation ability used Strat-M™ membrane with a transdermal diffusion system to evaluate the CTD and patch of CTD-12 (PCTD-12) within 24 hrs. PCTD-12 was used in a preliminary pharmacokinetic study in rats to demonstrate the potential of the developed transdermal nanocarrier drug patch for future applications. Results: In the transdermal application of CTD-12, the relative bioavailability of the formulation was 3.68 ± 0.17-fold greater than in the free CBD application. Moreover, PCTD-12 indicated 2.46 ± 0.18-fold higher relative bioavailability comparing with free CBD patch in the ex vivo evaluation. Most importantly, in the pharmacokinetics of PCTD-12, the relative bioavailability of PCTD-12 was 9.47 ± 0.88-fold higher than in the oral application. Conclusion: CTD-12, a transdermal nanocarrier, represents a promising approach for CBD delivery, suggesting its potential as an effective transdermal dosage form.