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.

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.

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.

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.

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.

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.

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.

Formulation and Characterization of Ethosomes for Transdermal Delivery of Prinsepia Utilis Rogle Seed Oil with Ameliorative Effects against UVB-Induced Skin Damage.

Prinsepia utilis seed oil (PUSO) is a natural medication obtained from Prinsepia utilis Rogle seed, which has been used for the treatment of skin diseases. The study aims to prepare ethosomes with high drug loading as a water-soluble transdermal vehicle to enhance the transdermal delivery of PUSO. PUSO-loaded ethosomes (PEs) were prepared using a cold method, and optimized by an orthogonal experimental design with entrapment efficiency (EE) as the dependent variable. The PEs prepared with the optimized formulation showed good stability, with a spherical shape under transmission electron microscopy (TEM), average particle size of 39.12 ± 0.85 nm, PDI of 0.270 ± 0.01, zeta potential of -11.3 ± 0.24 mV, and EE of 95.93 ± 0.43%. PEs significantly increased the skin deposition of PUSO compared to the PUSO suspension (P < 0.001). Moreover, the optimum formula showed significant ameliorative effects on ultraviolet B (UVB) irradiation-associated macroscopic and histopathological changes in mice skin. Therefore, PEs represent a promising therapeutic approach for the treatment of UVB-induced skin inflammation, with the potential for industrialization.

Topical drug delivery by Sepineo P600 emulgel: Relationship between rheology, physical stability, and formulation performance.

The objective of this present work was to develop and optimize oil-in-water (O/W) emulsion-based gels, namely emulgels that allow maximum topical drug delivery while having desired microstructure and acceptable physical stability. Emulgels containing 2.0 wt% lidocaine were prepared using various concentrations (0.75-5.0 wt%) of Sepineo P600. Their droplet size distribution, physical stability, rheological behaviors, in vitro drug release, and skin permeation profiles were evaluated. Results show that the concentration of Sepineo P600 significantly influenced the microstructure, rheology, and physical stability of the emulgel formulations. The physico-chemical properties also reveals that at least 1.0 wt% Sepineo P600 was needed to produce stable emulgel formulations. All formulations exhibited non-Newtonian shear-thinning properties which are desirable for topical applications. Both the release and permeation rates decreased with increasing viscosity and rigidity of the formulation. The lower the complex modulus of the emulgels, the higher the steady-state flux of the drug through the skin. Adding Sepineo P600 to emulgel systems resulted in increased rheological properties, which in turn slowed the diffusion of the drug for in vitro release. Although as expected skin permeation was rate limiting since in vitro release was 3 to 4 log-fold faster than skin flux. However, an interesting finding was that the derived skin/vehicle partition coefficient suggested the ionic interaction between lidocaine and Sepineo polymer reducing the free drug, i.e., thermodynamic activity and hence the flux with increasing Sepineo P600 concentration. Overall, this study has provided us with valuable insights into understanding the relationship between the microstructure (rheology), physical stability and skin drug delivery properties which will help to design and optimize topical emulgel formulations.

Evaluation of Emulgel and Nanostructured Lipid Carrier-Based Gel Formulations for Transdermal Administration of Ibuprofen: Characterization, Mechanical Properties, and Ex-Vivo Skin Permeation.

In transdermal applications of nonsteroidal anti-inflammatory drugs, the rheological and mechanical properties of the dosage form affect the performance of the drug. The aim of this study to develop emulgel and nanostructured lipid carrier NLC-based gel formulations containing ibuprofen, evaluate their mechanical properties, bioadhesive value and ex-vivo rabbit skin permeability. All formulations showed non-Newtonian pseudoplastic behavior and their viscosity values are suitable for topical application. The particle size of the nanostructured lipid carrier system was found to be 468 ± 21 nm, and the encapsulation efficiency was 95.58 ± 0.41%. According to the index of viscosity, consistency, firmness, and cohesiveness values obtained as a result of the back extrusion study, E2 formulation was found to be more suitable for transdermal application. The firmness and work of shear values of the E2 formulation, which has the highest viscosity value, were also found to be the highest and it was chosen as the most suitable formulation in terms of the spreadability test. The work of bioadhesion values of NLC-based gel and IBU-loaded NLC-based gel were found as 0.226 ± 0.028 and 0.181 ± 0.006 mJ/cm2 respectively. The percentages of IBU that penetrated through rabbit skin from the Ibuactive-Cream and the E2 were 87.4 ± 2.11% and 93.4 ± 2.72% after 24 h, respectively. When the penetration of ibuprofen through the skin was evaluated, it was found that the E2 formulation increased penetration due to its lipid and nanoparticle structure. As a result of these findings, it can be said that the NLC-based gel formulation will increase the therapeutic efficacy and will be a good alternative transdermal formulation.

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.

Cosmetically Approved Short-Chain Alcohol/Triethyl Citrate/Water Surfactant-Free Microemulsions and Potential Application to Transdermal Penetration of α-Arbutin.

Surfactant-free microemulsions (SFMEs) exhibited remarkable advantages and potential, attributed to their similarity to traditional surfactant-based microemulsions and the absence of surfactants. Herein, a novel SFME was developed utilizing cosmetically approved materials, such as short-chain alcohol as an amphi-solvent, triethyl citrate (TEC) as the nonpolar phase, and water as the polar phase. 1,2-Pentanediol (PtDO)/TEC/water combination can form the largest monophasic zone, accounting for ∼74% of the total phase diagram area, due to an optimal hydrophilic (water)-lipophilic (TEC) balance. Comparable to surfactant-based microemulsion, PtDO/TEC/water SFME can also be categorized into three types: water-in-oil, discontinuous, and oil-in-water. As TEC or water is increased, or PtDO is decreased, the nanoaggregates in PtDO/TEC/water SFME grow from <5 nm to tens of nanometers. The addition of α-arbutin (ABN) does not disrupt PtDO/TEC/water SFME, but rather enhances its formation, resulting in a larger monophasic area and consistent size (2.8-3.8 nm) through participating in interface assembly. Furthermore, ABN-loaded PtDO/TEC/water SFME exhibits remarkable resistance to dilution, exceptional stability, and minimal irritation. Notably, PtDO/TEC/water SFME significantly boosts ABN's solubility in water by 2 times, its percutaneous penetration rate by 3-4 times, and enables a slow-release DPPH• radical scavenging effect. This SFME serves as a safe and cosmetically suitable nanoplatform for the delivery of bioactive substances.

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.

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.

Carboxymethyl cellulose-based rotigotine nanocrystals-loaded hydrogel for increased transdermal delivery with alleviated skin irritation.

Transdermal rotigotine (RTG) therapy is prescribed to manage Parkinson's disease (Neupro® patch). However, its use is suffered from application site reactions. Herein, drug nanocrystalline suspension (NS)-loaded hydrogel (NS-HG) employing polysaccharides simultaneously as suspending agent and hydrogel matrix was constructed for transdermal delivery, with alleviated skin irritation. RTG-loaded NS-HG was prepared using a bead-milling technique, employing sodium carboxylmethyl cellulose (Na.CMC) as nano-suspending agent (molecular weight 90,000 g/mol) and hydrogel matrix (700,000 g/mol), respectively. NS-HG was embodied as follows: drug loading: ≤100 mg/mL; shape: rectangular crystalline; crystal size: <286.7 nm; zeta potential: -61 mV; viscosity: <2.16 Pa·s; and dissolution rate: >90 % within 15 min. Nuclear magnetic resonance analysis revealed that the anionic polymers bind to RTG nanocrystals via charge interaction, affording uniform dispersion in the matrix. Rodent transdermal absorption of RTG from NS-HG was comparable to that from microemulsions, and proportional to drug loading. Moreover, NS-HG was skin-friendly; erythema and epidermal swelling were absent after repeated application. Further, NS-HG was chemically stable; >95 % of the drug was preserved up to 4 weeks under long term (25 °C/RH60%), accelerated (40 °C/RH75%), and stress (50 °C) storage conditions. Therefore, this novel cellulose derivative-based nanoformulation presents a promising approach for effective transdermal RTG delivery with improved tolerability.

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.

Formulation characterization of lecithin organogel as topical drug delivery system for psoriasis: In-vitro permeation and preclinical evaluation.

Psoriasis is a chronic inflammatory and proliferative skin disease that causes pathological skin changes and has a substantial impact on the quality of patient life. Apremilast was approved by the US Food and Drug Administration as an oral medication for psoriasis and is beneficial in mild to moderate conditions for chronic usage. However, 5%-7% of withdrawals were reported due to severe side effects. To address the issue, a localized drug delivery strategy via the topical route may be a viable approach. However, poor physicochemical properties make it vulnerable to passing through the skin, requiring a specialized drug delivery system to demonstrate its full potential via a topical route like lecithin organogel. The formulation was optimized by screening the suitable lecithin type and non-polar solvents based on the gel formation ability of lecithin and the solubility of apremilast in the solvent. The pseudo-ternary diagram was used to optimize the water content required to form the gel. The optimized gel was found to be shear thinning characterized for rheological parameters, in-vitro diffusion studies, and in-vitro skin distribution studies. Preclinical studies in Imiquimod-induced mice showed a better reduction in severity index, cytokine levels, and epidermal hyperplasia from the lecithin organogel group compared to the apremilast oral administration and marketed standard topical gel group. Based on these results, lecithin organogel can be considered a promising approach to deliver molecules like apremilast by topical route in psoriatic-like conditions.

QbD Based Formulation Development and Optimisation of Ozenoxacin Topical Nano-Emulgel and Efficacy Evaluation Using Impetigo Mice Model.

To formulate and optimize Ozenoxacin nano-emulsion using Quality by Design (QbD) concept by means of Box-Behnken Design (BBD) and converting it to a gel to form Ozenoxacin nano-emulgel followed by physico-chemical, in-vitro, ex-vivo and in-vivo evaluation. This study demonstrates the application of QbD methodology for the development and optimization of an effective topical nanoemulgel formulation for the treatment of Impetigo focusing on the selection of appropriate excipients, optimization of formulation and process variables, and characterization of critical quality attributes. BBD was used to study the effect of "% of oil, % of Smix and homogenization speed" on critical quality attributes "globule size and % entrapment efficiency" for the optimisation of Ozenoxacin Nano-emulsion. Ozenoxacin loaded nano-emulgel was characterized for "description, identification, pH, specific gravity, amplitude sweep, viscosity, assay, organic impurities, antimicrobial effectiveness testing, in-vitro release testing, ex-vivo permeation testing, skin retention and in-vivo anti-bacterial activity". In-vitro release and ex-vivo permeation, skin retention and in-vivo anti-bacterial activity were found to be significantly (p < 0.01) higher for the nano-emulgel formulation compared to the innovator formulation (OZANEX™). Antimicrobial effectiveness testing was performed and found that even at 70% label claim of benzoic acid is effective to inhibit microbial growth in the drug product. The systematic application of QbD principles facilitated the successful development and optimization of a Ozenoxacin Nano-Emulsion. Optimised Ozenoxacin Nano-Emulgel can be considered as an effective alternative and found to be stable at least for 6 months at 40 °C / 75% RH and 30 °C / 75% RH.