Topical Vehicle Research Articles

Topical calcineurin and mammalian target of rapamycin inhibitors in inflammatory dermatoses: Current challenges and nanotechnology‑based prospects (Review).

Topical therapy remains a critical component in the management of immune‑mediated inflammatory dermatoses such as psoriasis and atopic dermatitis. In this field, macrolactam immunomodulators, including calcineurin and mammalian target of rapamycin inhibitors, can offer steroid‑free therapeutic alternatives. Despite their potential for skin‑selective treatment compared with topical corticosteroids, the physicochemical properties of these compounds, such as high lipophilicity and large molecular size, do not meet the criteria for efficient penetration into the skin, especially with conventional topical vehicles. Thus, more sophisticated approaches are needed to address the pharmacokinetic limitations of traditional formulations. In this regard, interest has increasingly focused on nanoparticulate systems to optimize penetration kinetics and enhance the efficacy and safety of topical calcineurin and mTOR inhibitors in inflamed skin. Several types of nanovectors have been explored as topical carriers to deliver tacrolimus in both psoriatic and atopic skin, while preclinical data on nanocarrier‑based delivery of topical sirolimus in inflamed skin are also emerging. Given the promising preliminary outcomes and the complexities of drug delivery across inflamed skin, further research is required to translate these nanotherapeutics into clinical settings for inflammatory skin diseases. The present review outlined the dermatokinetic profiles of topical calcineurin and mTOR inhibitors, particularly tacrolimus, pimecrolimus and sirolimus, focusing on their penetration kinetics in psoriatic and atopic skin. It also summarizes the potential anti‑inflammatory benefits of topical sirolimus and explores novel preclinical studies investigating dermally applied nanovehicles to evaluate and optimize the skin delivery, efficacy and safety of these 'hard‑to‑formulate' macromolecules in the context of psoriasis and atopic dermatitis.

Efficacy and safety of Ruxolitinib, Crisaborole, and Tapinarof for mild-to-moderate atopic dermatitis: a Bayesian network analysis of RCTs.

Given the lack of head-to-head studies of novel non-steroidal molecule topical therapies in mild-to-moderate atopic dermatitis (AD), network meta-analyses (NMAs) can provide comparative efficacy and safety data for clinical decision-making. In this NMA, we performed a literature search until 01 March 2023 for eligible studies written in English using databases, including PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov. Only double-blind randomized clinical trials (RCTs) with topical Ruxolitinib, Crisaborole, or Tapinarof versus vehicle for patients with mild-to-moderate AD were included. Baseline and follow-up data were extracted. Efficacy was evaluated using Investigator's Global Assessment (IGA) achieving "clear" or "almost clear," with 2 points or more improvement from baseline at the end of treatment, referred to as "IGA success." For binary outcomes, we analyzed in random-effects Bayesian NMA consistency models to compare the efficacy of these 3 topical therapies by odds ratio (OR) with 95% credibility interval (CrI). Overall, 10 phase 2 or phase 3 RCTs were identified, which included 4010 patients with mild to moderate AD. Compared with the topical vehicle control, all these 3 treatments had higher response rate of "IGA success" at the end of trial (Ruxolitinib 1.5% b.i.d: OR, 11.94; 95%CrI, 6.28-23.15; Crisaborole 2% b.i.d: OR, 2.08; 95%CrI, 1.46-3.52; Tapinarof 1% b.i.d: OR, 2.64; 95%CrI, 0.75-9.70). Notably, Ruxolitinib 1.5% b.i.d. had the highest probability of achieving "IGA success" in ranking analysis (Rank 1, SUCRA = 0.75) and lower risk of AE (Rank 8, SUCRA = 0.22). Besides, there was no difference in treatment-related adverse events between 3 therapies. Heterogeneity was not significant across studies.

Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation

To assess the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed after high-risk corneal transplantation. Secondary analysis of prospective, randomized, double-blind, placebo-controlled multicentric clinical trial. The study includes patients aged > 18 years who underwent high-risk penetrating keratoplasty, which was defined as corneal vascularization in ≥ 1 quadrants of the corneal graft and host bed, excluding the limbus. Patients were randomized to treatment and control groups. The patients in the treatment group received subconjunctival injection of bevacizumab (2.5 mg/0.1 ml) on the day of the procedure, followed by topical bevacizumab (10 mg/ml) 4 times per day for 4 weeks. The patients in control group received injection of vehicle (0.9% sodium chloride) on the day of procedure, followed by topical vehicle (carboxymethylcellulose sodium 1%) 4 times a day for 4 weeks. Vessel and invasion area of vessels in the corneal graft and host beds. This study included 56 eyes of 56 patients who underwent high-risk corneal transplantation, with equal numbers in the bevacizumab and vehicle (control) treatment groups. The mean age of patients who received bevacizumab was 61.2 ± 15.9 years, and the mean age of those treated with vehicle was 60.0 ± 16.1 years. The vessel area at baseline was comparable in the bevacizumab (16.72% ± 3.19%) and control groups (15.48% ± 3.12%; P= 0.72). Similarly, the invasion areas were also similar in the treatment (35.60% ± 2.47%) and control (34.23% ± 2.64%; P= 0.9) groups at baseline. The reduction in vessel area was significantly higher in the bevacizumab-treated group (83.7%) over a period of 52 weeks compared with the control group (61.5%; P < 0.0001). In the bevacizumab-treated group, invasion area was reduced by 75.8% as compared with 46.5% in the control group. The vessel area was similar at 52 weeks postprocedure in cases of first (3.54% ± 1.21%) and repeat (3.80% ± 0.40%) corneal transplantation in patients who received bevacizumab treatment. In the vehicle-treated patients, the vessel area was significantly higher in repeat (9.76% ± 0.32%) compared with first (8.06% ± 1.02%; P < 0.0001) penetrating keratoplasty. In the bevacizumab treatment group, invasion areas at week 52 were comparable in first (11.70% ± 3.38%) and repeat (11.64% ± 1.74%) procedures, whereas invasion area was significantly higher in repeat (27.87% ± 2.57%) as compared with first (24.11% ± 2.17%) penetrating keratoplasty in vehicle-treated patients. In patients undergoing vascularized high-risk corneal transplantation, bevacizumab is efficacious in reducing vascularization of corneal graft and host bed, thereby reducing the risk of corneal graft rejection in vascularized host beds. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluation of the in-vitro antifungal activity of Holoptelea Integrifolia ethanolic extract loaded in microemulsion

Microemulsions improve the transdermal delivery of several drugs over conventional topical preparations such as emulsions and gels: enhanced drug solubilization, increased skin flux, and decreased diffusion coefficient. Microemulsion-based systems find significant improvement in the topical delivery of antifungals. We believe that drug-loaded microemulsion will show better antifungal activity by better penetration into the skin and fungal cells. Antifungal agents are mostly lipophilic and easily formulated in topical vehicles. Microemulsions were prepared by the phase titration method. Formulations of the same drug and Excipient ratio and different concentrations were optimized with selected parameters like pseudo ternary phase diagram, particle analysis size, zeta potential validation, entrapment efficiency, and drug release studies performed by dialysis bag diffusion techniques at a temperature (37ºC). The study continued for 24 hours. The maximum amount of drug Holoptelea integrifolia release is 90% within 8hr. The study was monitored at 37ºC. Successfully done preparation, characterization, and drug release study of Microemulsion drug loaded.

Collagen mimetic peptide repair of the corneal nerve bed in a mouse model of dry eye disease.

The intraepithelial sub-basal nerve plexus of the cornea is characterized by a central swirl of nerve processes that terminate between the apical cells of the epithelium. This plexus is a critical component of maintaining homeostatic function of the ocular surface. The cornea contains a high concentration of collagen, which is susceptible to damage in conditions such as neuropathic pain, neurotrophic keratitis, and dry eye disease. Here we tested whether topical application of a collagen mimetic peptide (CMP) is efficacious in repairing the corneal sub-basal nerve plexus in a mouse model of ocular surface desiccation. We induced corneal tear film reduction, epithelial damage, and nerve bed degradation through a combination of environmental and pharmaceutical (atropine) desiccation. Mice were subjected to desiccating air flow and bilateral topical application of 1% atropine solution (4× daily) for 2 weeks. During the latter half of this exposure, mice received topical vehicle [phosphate buffered saline (PBS)] or CMP [200 μm (Pro-Pro-Gly)7, 10 μl] once daily, 2 h prior to the first atropine treatment for that day. After euthanasia, cornea were labeled with antibodies against βIII tubulin to visualize and quantify changes to the nerve bed. For mice receiving vehicle only, the two-week desiccation regimen reduced neuronal coverage of the central sub-basal plexus and epithelial terminals compared to naïve, with some corneas demonstrating complete degeneration of nerve beds. Accordingly, both sub-basal and epithelial βIII tubulin-labeled processes demonstrated increased fragmentation, indicative of nerve disassembly. Treatment with CMP significantly reduced nerve fragmentation, expanded both sub-basal and epithelial neuronal coverage compared to vehicle controls, and improved corneal epithelium integrity, tear film production, and corneal sensitivity. Together, these results indicate that topical CMP significantly counters neurodegeneration characteristic of corneal surface desiccation. Repairing underlying collagen in conditions that damage the ocular surface could represent a novel therapeutic avenue in treating a broad spectrum of diseases or injury.

In Vivo Study of the Effects of Propranolol, Timolol, and Minoxidil on Burn Wound Healing in Wistar Rats.

Propranolol, timolol, and minoxidil have all shown benefits in treatment of burn injury and other skin wounds. The study evaluated their effects on full-thickness thermal skin burns in a Wistar rat model. Performed on 50 female rats; two dorsal skin burns were created on each animal. On the next day, the rats were divided into 5 groups (n=10); each has received a specific treatment daily for 14 days: group I - topical vehicle (control), group II - topical silver sulfadiazine (SSD), group III - oral propranolol (5.5mg) associated with topical vehicle, group IV - topical timolol 1% cream, group V - topical minoxidil 5% cream. Wound contraction rates, malondialdehyde (MDA), glutathione (GSH, GSSG), and catalase activity in skin and/or serum were evaluated, and histopathological analyses were performed. Propranolol did not show advantages in necrosis prevention and wound contraction and healing, and did not reduce oxidative stress. It impaired keratinocyte migration, and promoted ulceration, chronic inflammation, and fibrosis, yet reducing the necrotic zone. Timolol prevented necrosis and promoted contraction and healing, increased antioxidant capacity and promoted keratinocyte migration and neo capillarization in comparison to the other treatments. Minoxidil reduced necrosis and enhanced contraction, resulting in positive outcomes after 1 week of treatment regarding local antioxidant defense, keratinocyte migration, neo capillarization, chronic inflammation, and fibrosis rates. However, after 2 weeks, it resulted in contrasting outcomes. In conclusion, topical timolol promoted wound contraction and healing, reducing local oxidative stress and improving keratinocyte migration, bringing arguments for potential benefits in skin epithelization.

Patient-Centric Design of Topical Dermatological Medicines.

Topical treatments are essential approaches to skin diseases but are associated with poor adherence. Topical vehicles have the primary purpose of ensuring drug effectiveness (by modulating drug stability and delivery, as well as skin properties) but have a marked impact on treatment outcomes as they influence patient satisfaction and, consequently, adherence to topical treatments. There is also a wide variety of vehicles available for topical formulations, which can complicate the decisions of clinicians regarding the most appropriate treatments for specific skin disorders. One of the possible strategies to improve topical-treatment adherence is the implementation of patient-centric drug-product design. In this process, the patient's needs (e.g., those related to motor impairment), the needs associated with the disease (according to the skin lesions' characteristics), and the patient's preferences are taken into consideration and translated into a target product profile (TPP). Herein, an overview of topical vehicles and their properties is presented, along with a discussion of the patient-centric design of topical dermatological medicines and the proposal of TPPs for some of the most common skin diseases.

Deep Eutectic Liquids as a Topical Vehicle for Tadalafil: Characterisation and Potential Wound Healing and Antimicrobial Activity.

Deep eutectic solvents (DESs) and ionic liquids (ILs) offer novel opportunities for several pharmaceutical applications. Their tunable properties offer control over their design and applications. Choline chloride (CC)-based DESs (referred to as Type III eutectics) offer superior advantages for various pharmaceutical and therapeutic applications. Here, CC-based DESs of tadalafil (TDF), a selective phosphodiesterase type 5 (PDE-5) enzyme inhibitor, were designed for implementation in wound healing. The adopted approach provides formulations for the topical application of TDF, hence avoiding systemic exposure. To this end, the DESs were chosen based on their suitability for topical application. Then, DES formulations of TDF were prepared, yielding a tremendous increase in the equilibrium solubility of TDF. Lidocaine (LDC) was included in the formulation with TDF to provide a local anaesthetic effect, forming F01. The addition of propylene glycol (PG) to the formulation was attempted to reduce the viscosity, forming F02. The formulations were fully characterised using NMR, FTIR and DCS techniques. According to the obtained characterisation results, the drugs were soluble in the DES with no detectable degradation. Our results demonstrated the utility of F01 in wound healing in vivo using cut wound and burn wound models. Significant retraction of the cut wound area was observed within three weeks of the application of F01 when compared with DES. Furthermore, the utilisation of F01 resulted in less scarring of the burn wounds than any other group including the positive control, thus rendering it a candidate formula for burn dressing formulations. We demonstrated that the slower healing process associated with F01 resulted in less scarring potential. Lastly, the antimicrobial activity of the DES formulations was demonstrated against a panel of fungi and bacterial strains, thus providing a unique wound healing process via simultaneous prevention of wound infection. In conclusion, this work presents the design and application of a topical vehicle for TDF with novel biomedical applications.

Breaking the Frustrating Cycle of Topical Steroids in Psoriasis: A Review of a Novel Vehicle for Fixed-Dose Combination Halobetasol Propionate/Tazarotene.

Topical therapies are commonly used to treat psoriasis, either as monotherapy for milder disease or as adjuncts to systemic and biologic drugs. Topical steroids and tazarotene are both options for topical psoriasis treatment, but as monotherapies, they are associated with adverse events (AEs) that make adherence to prescribed treatment challenging. In addition, the topical vehicles may have an unappealing appearance or texture that proves impractical for patients. Consequently, patients may not use treatments as prescribed. This noncompliance can lead to a frustrating cycle of treatment, discontinuation, and retreatment without achieving treatment goals. Psoriasis is a chronic disease; thus, topical treatment options are needed that address these barriers to use and promote long-term adherence, making satisfactory improvement of psoriasis more attainable. In this review, we discuss patient preferences for topical therapies with vehicles that are moisturizing, nongreasy, and quickly absorbed. We then introduce the vehicle formulation of fixed-dose combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion, which has a unique matrix mesh formulation that enhances uniform absorption, allows for efficient drug delivery, and aligns with patient preferences. In addition to vehicle benefits, the combination of HP and TAZ has been shown to minimize AEs seen with either monotherapy. In clinical trials, HP/TAZ was efficacious and associated with a low rate of AEs with long-term use. This evidence supports the use of HP/TAZ as a topical treatment for patients with psoriasis facing challenges adhering to prescribed treatments and looking to break the cycle of unsatisfactory treatment outcomes. J Drugs Dermatol. 2023;22(3):247-251. doi:10.36849/JDD.7399.

Effects of Various Emulsifying Agent and Permeability Enhancer on Percutaneous Absorption of Novel Microemulsion-Based Cream

Terbinafine hydrochloride is an antifungal drug used in the treatment of fungal infections. The oral use of terbinafine hydrochloride is not recommended as it has many potential side effects and undergoes hepatic first pass metabolism. Topical route of application has a great potential as an effective and safe way to administer drug for its antifungal in effect. The concentration of surfactant and permeation enhancer significantly affects the critical parameters of cream formulation like flux, cumulative amount released at 12 hours and enhancement ratio. In vitro permeation study across rat epidermal membrane showed that menthol enhanced the transdermal absorption of drug from cream formulation. The topical cream formulation developed in this study holds the promise for the further in vivo studies. The aim of the present work under investigation is to check the effects of emulsifying agents (Cremophor RH40, Tween 60) and permeation enhancers (l-Menthol) on cream. Developing a formulation that is safe and can deliver the drug locally in an effective concentration for its effect. The development of topical antifungal drug delivery systems designed to have localized effects appears to be very advisable and beneficial over conventional routes of provides the drug administration. However, due to the relative impermeability of the stratum corneum, which principal resistance to percutaneous absorption, extensive studies are generally necessary in order to optimize both the release of the drug from the topical vehicle and skin permeation further, A topical formulation must be both physically and chemically stable, this require numerous excipients. Aesthetically pleasing, in addition to being properties, hence they play emulsifying agents and permeation enhancers have major influence on these important role.&#x0D; Keywords: Emulsifying agents, Permeation enhancers, Stratum corneum, Antifungal, Topical cream

Development, characterization, and evaluation by cutaneous bioengineering of a natural emulsion, to provide a standardized vehicle base for topical compounded preparations

The use of products containing natural and sustainable substances has shown a remarkable growth in the pharmaceutical and cosmetic market, such as in the compounding pharmacy. This research aimed to develop, characterize, and evaluate the cutaneous bioengineering of natural and sustainable emulsions, providing a vehicle base for topical preparations. Nine O/W emulsions were developed changing the nonionic self-emulsifying wax (Cetearyl Olivate (and) Sorbitan Olivate, Cetearyl Glucoside (and) Cetearyl Alcohol, Candelilla/Jojoba/Rice Bran Polyglyceryl-3 Esters (and) Glyceryl Stearate (and) Cetearyl Alcohol (and) Sodium Stearoyl Lactylate), with or without the anionic co-emulsifier (Sodium Stearoyl Glutamate). They were characterized through preliminary stability tests, rheology and accelerated physicochemical stability study. Four formulations were approved (FB1, FB2, FB3 and FB5), but only FB1 (Cetearyl Olivate (and) Sorbitan Olivate with Sodium Stearoyl Glutamate) was considered stable, being selected for preservative efficacy evaluation and the cutaneous bioengineering. The hydration and transepidermal water loss (TEWL) of stratum corneum were analyzed comparing with a conventional topical vehicle (Emulsifying Wax NF). The clinical study showed that FB1 improved the skin hydration with no significant changes for TEWL, but demonstrated considered values. The FB1 could be classified as “skin friendly” and represents a promising natural and sustainable vehicle in compounded pharmacy preparations.

A Free Fatty Acid Synthetic Agonist Accelerates Wound Healing and Improves Scar Quality in Mice.

Impaired wound healing is a health problem around the world, and the search for a novel product to repair wounded skin is a major topic in the field. GW9508 is a synthetic molecule described as a selective agonist of free fatty acid receptors (FFARs) 1 and 4, and there is evidence of its anti-inflammatory effects on several organs of the body. Here, we aimed to evaluate the effects of topical GW9508 on wound healing in mice. First, we used bioinformatic methods to determine the expression of FFAR1 and FFAR4 mRNA in the skin from a human cell atlas assembled with single-cell transcriptomes. Next, we employed 6-week-old C57BL6J mice with 2 wounds inflicted in the back. The mice were randomly divided into 2 groups, a control group, which received topical vehicle, and a treatment group, which received GW9508, for 12 days. The wound was monitored by photographic documentation every 2 days, and samples were collected at day 6 and 12 post injury for RT-PCR, western blot and histology analyses. FFAR1 and FFAR4 mRNA are expressed in skin cells in similar amounts to those in other tissues. Topical GW9508 accelerated wound healing and decreased gene expression of IL-10 and metalloproteinase 9 on days 6 and 12 post injury. It increased the quantity of Collagen I and improved the organization of collagen fibres. Conclusions: Our results show that GW9508 could be an attractive drug treatment for wounded skin. Future studies need to be performed to assess the impact of GW9508 in chronic wound models.

Formulation, characterization of glucosamine loaded transfersomes and in vivo evaluation using papain induced arthritis model

The aim of current study was to develop the transdermal transfersomes of glucosamine for better drug delivery. Stretch ability and plasticity of transfersomes membranes mitigate the risk of vesicle rupture in the skin and allows the drug carrying transfersome to pass through the epidermis following the natural water gradient. Transdermal delivery of Glucosamine has an advantage over oral route, having greater local concentration and fewer systemic effects. Thin Film Rotary method was use to prepare transfersomes, and characterization was carried out physio-chemically using electron microscopic studies, zeta potential evaluation, entrapment efficiency studies. To add on in the stability, development of a secondary topical vehicle using Carbopol 940 was carried out to enhance the shelf life of transfersomes. Furthermore, in vivo studies on rabbits were also carried out using the papain induced arthritis model to support the effectiveness of treatment. The radiology studies of knee joint of rabbits proved the effectiveness of glucosamine loaded transfersomes in healing the osteoarthritis with the blood plasma analysis remain unaltered. In vitro characterization showed the successful development of nano-deformable entities with good entrapment efficiency but with little stability, therefore modified into a gel. In a nut shell this modified new dosage from can be best alternative to other conventional options that owe lot of demerits.

The Effect of Various Vehicles on the In Vitro Skin Permeability of Minoxidil

Background: This study aimed to examine the uptake of the model therapeutic agent, minoxidil, through the skin, under the influence of different vehicles. Therefore, the effect of different penetration enhancers such as Propylene glycol, water, ethanol, transcutol P, caprylic acid, and Isopropyl alcohol were evaluated on skin permeability of minoxidil through rat skin. Methods: The skin permeability of minoxidil on rat skin was analyzed through a Franz cell by evaluating the parameters, including Jss, ERflux, ERD, and ERp. The enhancement mechanisms were studied by comparing FT-IR peak intensities for asymmetric and symmetric C-H stretching, ester C=O stretching, and Amide peaks. The mean transition temperature (Tm) and their enthalpies (ΔH) were investigated by the DSC technique. Results: Caprylic acid had the highest diffusion coefficient enhancement ratio (ERD), followed by propylene glycol and water. All solvents have ERD flux enhancement ratio. Solubility in the stratum corneum limited partitioning. All carriers enhanced drug permeability from rat skin, according to FTIR and DSC. Conclusions: Caprylic acid is an effective topical vehicle for minoxidil due to greater partitioning and diffusion through rat skin.

Effect of secretome of adipose stem cell (ASC) in photoaging skin

Introduction: UV light is the principal cause of photoaging, a kind of aging. The problem arises because it is less enjoyable. Utilizing the secretome of adipose stem cells (ASC), which is rich in growth factors, could be a novel anti-photoaging therapy. The secretome of ASCs has been extensively examined for their role in wound healing, but their function in photoaging has just lately been investigated. This study looked at changes in epidermal and dermal thickness, expression of MMP-1 and TIMP-1, as well as dermal collagen density to assess the influence of the secretome of ASC in photoaging treatment. Methods: 28 male Wistar rats, 10-12 weeks old, were randomly assigned to one week of acclimation in each of four groups: UV-irradiated group with topical secretome of ASC (Group P1); UV-irradiated group with topical vehicle only (Group P2); only topical secretome of ASC, non-UV-irradiated (Group P3); and non-UV-irradiated and no topical treatment (Group P4) (Group P0). Prior to treating the rats, the UV exposure was administered for six weeks. Then, for a period of four weeks, the secretome ASC was administered as a treatment. Results: The epidermal and dermal thickness were significantly improved after four weeks treatment compared to UV irradiated with topical vehicle only group (p&lt;0.05). The expression of TIMP-1 and dermal collagen density were significantly increased (p&lt;0.05). Conclusion: Secretome of ASC may be a solution for photoaging skin.

Improving the outcome of treating striae gravidarum by combined therapies using topical β-glucan and 1565-nm non-ablative fractional laser: A prospective randomized vehicle-controlled parallel group study.

Striae gravidarum (SG) is a kind of dermal scar associated with psychosocial and therapeutic challenge. Topical reagents and non-invasive laser are more preferred than invasive procedures for less pain and shorter downtime. However, there are few studies on comparing and combining these two modalities. The aim of the present study was to evaluate the efficacy and tolerance of a topical regimen containing β-glucan, 1565-nm non-ablative fractional laser (NAFL; ResurFX), and combination of them for SG. A total of 128 unilateral abdomens from 64 subjects were randomly divided into four strategies and were followed up for 12 weeks: topical vehicle (Veh); topical β-glucan (B); 1565-nm NAFL combined topical vehicle (NAFL); 1565-nm NAFL combined topical β-glucan (B + NAFL). NAFL was applied three times with a 4-week interval. Topical reagent was applied b.i.d. for 12 weeks. Global Aesthetic Improvement Scale (GAIS) scores were assessed by blinded physician according to standard photograph, and by subjects at 12th week. The degree of SG atrophy was assessed by blinded physician before treatment and at the 12th week according to a standard 5-point scale. Collagen remodeling was evaluated by histological analysis and all adverse effects were recorded. A total of 56 women (112 unilateral abdomens) completed all study. The GAIS scores by blinded physician showed greater improvement in NAFL as compared with β-glucan, and by subjects showed greater improvement in β-glucan as compared with vehicle. In terms of striae atrophy scale, the improvement of SG atrophy was more prominent in NAFL compared to β-glucan, and in β-glucan + NAFL compared to Veh + NAFL. All treatments were well tolerated. Topical β-glucan regimen can mildly improve SG. NAFL showed better results than topical β-glucan regimen. The combined strategy may further improve the SG atrophy compared with single treatment strategy.

Part 1 results from NOVA-II, a randomized, double-blind, vehicle-controlled phase II study evaluating the safety and efficacy of OQL011 on VEGFR inhibitor associated hand-foot skin reaction in cancer patients.

TPS396 Background: Hand-foot skin reaction (HFSR) is associated with the use of multi-targeted tyrosine kinase inhibitors sharing vascular endothelial growth factor receptor inhibitory (VEGFRi) activity (e.g., cabozantinib, regorafenib, sorafenib, sunitinib). HFSR affects the palms and soles with edema, erythema, hyperkeratosis, pain, and bullae/blisters impacting quality-of-life, activities of daily living, and consistent VEGFRi dosing. HFSR incidence differs among VEGFRi, ranging from 5-69% (all grades) and 1-19% (grade 3). Topical urea has marginal benefit, and to date, there are no regulatory authority approved HFSR treatments. The pathogenesis of HFSR has been partially associated with impaired vascular repair mechanisms resulting from inhibition of VEGF signaling. Nitric oxide (NO) has been reported to induce VEGF upregulation at a moderate concentration. We hypothesized that topical stimulation of VEGF signaling through OQL011, an NO donor, will safely and effectively mitigate HFSR. Methods: NOVA-II is a phase 2, double-blind, randomized vehicle-controlled trial evaluating the safety and efficacy of OQL011 for the treatment of moderate to severe HFSR. Subjects receiving a VEGFRi (either mono- or combination therapy) and have Grade ≥2 HFSR per NCI CTCAE v5.0 for palmar plantar erythrodysesthesia (PPE) were eligible. For Part 1, 31 subjects were randomized (2:1) and received 0.2% OQL011 topical ointment or vehicle TID for 6 weeks. The primary endpoint is the proportion of patients who achieve an NCI CTCAE v5.0 for PPE Grade 0 or 1 by Week 3. An investigator global assessment (IGA) scale is being developed to assess HFSR recovery, and a secondary endpoint will measure the proportion of patients who have improvement in HFSR severity and achieve an IGA score of clear (0) or almost clear (1) by Week 3 and/or Week 6. A Chi-square test will be used to detect a difference between the treatment arm and the vehicle-control arm. Additionally, the IGA score will be validated by assessing the inter- &amp; intra-rater reliability. The correlation between IGA, NCI CTCAE v5.0 for PPE, and patient outcomes including Visual Analog Scale of Pain, HFSR Quality of Life questionnaire will also be reported. This study began enrolling patients in December 2019 and completed the last patient Visit in August 2021. Data lock, unblinding and data analysis will be completed by mid-November. Clinical trial information: NCT04088318.

An eco-friendly zein nanoparticle as robust cosmetic ingredient ameliorates skin photoaging

Zein colloidal particles, which have generally regarded as safe (GRAS) status, have been routinely used in formulations of oral nutraceuticals but not in skin care products. Herein, we constructed for the first time zein-based topical vehicles to address skin photoaging. To this end, we fabricated a new type of eco-friendly nanoparticles by co-assembling zein with hyaluronic acid (HA), a cell-specific molecule, to encapsulate hydrophobic tetrahydrocurcumin (THC) with an aim to improve its cutaneous bioavailability. Impressively, the prepared nanoparticles could increase the solubility of THC in water by 72.84 times, and were stable at pH 4–10. In particular, the topical delivery systems were effective in UVB-induced cell and animal photoaging models, and were able to restore the accumulation of matrix metalloproteinase-1 (MMP-1) and inflammatory factors to the normal levels at the selected conditions. In addition, the biotransformation of THC in HaCaT cells was observed and clarified. This strategy may open up new promising avenues for developing innovative nanocosmetics containing anti-photoaging ingredient.

Safety Assessment of a Novel Topical Vehicle for Personalized Treatments in Acne

Acne vulgaris is a common inflammatory disease of the pilosebaceous unit, with a profound impact on the quality of life of patients. In this work, we aimed to study the safety characteristics of CleodermTM, a novel functional semisolid vehicle developed for the compounding of treatments for acne and oily skin. The primary and cumulative irritation and sensitization potential were evaluated in 54 healthy volunteers in a comparative single-blinded study, while the acnegenic and comedogenic potential of the product were assessed in 31 healthy volunteers with combination to oily skin through a non-comparative study. CleodermTM was applied (0.05 g/cm2) in filter paper discs in both studies. For the evaluation of the irritation and sensitization potential, the investigational product, or a control (0.9% NaCl) was applied to the right or left scapular area of the study subjects. No clinical reactions were observed during the induction or challenge phases, suggesting that CleodermTM presents no irritating or allergenic potential. Regarding acnegenicity and comedogenicity, no significant increase in the number of acne lesions linked to the application of the product in four areas of the face was reported, indicating that CleodermTM appears not to display acnegenic and comedogenic potential. Furthermore, over 60% of the study subjects exhibited a decrease in the number of acne lesions after product use. These results show that CleodermTM exhibited no irritating, sensitizing, acnegenic or comedogenic potential, and suggest that it can be considered safe under the study conditions and that the claims dermatologically tested, clinically tested, and non-comedogenic/acnegenic can be supported.

Vehicles for Drug Delivery and Cosmetic Moisturizers: Review and Comparison.

Many dermatological conditions, such as eczema and psoriasis, are treated with topical therapeutic products. Instead of applying the active drug directly onto the skin, it is combined with a vehicle to aid in its delivery across the stratum corneum (SC) and into deeper regions of the skin, namely the epidermis and dermis. Absorption into the systemic circulation is minimized. Topical vehicles are also used as cosmetic moisturizers (often termed emollient therapy) to ameliorate dry skin, which is a cornerstone of the management of various dermatological conditions, including xerosis, eczema, psoriasis, and aging. The most common topical vehicles include ointments, creams, gels, and lotions, among others. It is crucial that topical vehicles are chosen based upon the size and properties (wet/dry, mucous/non-mucous, healthy/diseased) of the skin to be treated in order to optimize application and contact of the product with the skin, as this can have profound impacts on potency, efficacy, and patient compliance. This review examines common topical vehicles used for drug delivery and cosmetic moisturizers, including their formulation, advantages and disadvantages, and effects on the skin. The unique rules imposed by governing regulatory bodies in Australia and around the world, in terms of topical product claims, are also briefly examined.