Topical Medications Research Articles

Evaluation of ocular tolerability and bioavailability of tonabersat transfersomes ex vivo.

While transfersomes (TFS) have extensively been investigated as carriers for topical drug delivery to the skin, their application in ocular drug delivery remains largely unexplored. This study aimed to evaluate the tolerability, contact angle, and ocular penetration of tonabersat-loaded TFS using ex vivo models, with a focus on comparing drug distribution in different ocular tissues. A solution of tonabersat in medium chain triglycerides (MCT) was used as the control. Conjunctival tolerability was evaluated using the Hen's Egg Test on Chorioallantoic Membrane (HET-CAM), while the Bovine Corneal Opacity and Permeability (BCOP) assay was used to establish corneal tolerability. Drop contact angle on freshly excised bovine corneas was measured using a goniometer. Drug penetration into the cornea, conjunctiva, eyelid and sclera-choroid was evaluated using an ex vivo porcine whole eye model under simulated tear flow, 0.25, 0.5, 1, and 2h after eyedrop application. Both the TFS and MCT formulations exhibited good conjunctival and corneal tolerability with the TFS contact angle on the corneal surface being lower than that of MCT. Significantly greater drug concentrations were achieved in all ocular tissues with the TFS eyedrop, with the Cmax from TFS being at least 16-fold higher than that achieved with the MCT solution in the conjunctiva, eyelid and sclera-choroid, with the difference being greatest in the latter. Meanwhile, the corneal Cmax was 6-fold greater with TFS. Interestingly, despite simulated tear flow, the Tmax was observed at a later timepoint with TFS in all ocular tissues. Overall, this study demonstrates that TFS are well tolerated on the ocular surface and have the potential for sustained and targeted drug delivery to ocular tissues. Thus, they present a promising alternative for safe and effective ocular drug delivery.

Cyclic cell-penetrating peptide-engineered ceria nanoparticles for non-invasive alleviation of ultraviolet radiation-induced cataract

Oxidative stress, which results from the accumulation of free radicals, plays a substantial role in cataract formation. Antioxidants have shown promise in mitigating or even preventing this process. However, delivering antioxidants noninvasively to the anterior segment of the eye has been a significant challenge. In this study, we developed ceria nanoparticles modified with cyclic cell-penetrating peptides to overcome the obstruction of the dense corneal barrier on topical drug delivery. Our results demonstrated that modified ceria nanoparticles with cell-penetrating peptides (CPPs) facilitate the opening of tight junctions in human corneal epithelial cells. This characteristic considerably enhances the trans-corneal transport of nanoparticles and improves cellular uptake efficiency, while also contributing to their intracellular enrichment toward mitochondria. Further experiments confirmed that the modified ceria nanoparticles effectively counteracted ferroptosis induced by oxidative stress in lens epithelial cells both in vitro and in vivo, substantially reducing cataract formation. The successful development of ceria nanoparticles modified with cyclic cell-penetrating peptides (cCPPs) opens new avenues for research in cataract prevention and treatment. Additionally, the modified ceria nanoparticles could serve as a noninvasive drug delivery system, which holds remarkable potential for advancing drug delivery in diseases affecting the anterior segment of the eye.Graphical

Folliculitis decalvans. Possibilities of combined therapy with 308 nm UVB: clinical cases

Folliculitis decalvans is a rare neutrophilic cicatricial alopecia of the scalp. As it is a progressive inflammatory disease characterized by a gradual increase in the area of inflamed follicles with the formation of areas of cicatricial alopecia in the outcome. The most common clinical manifestations of folliculitis decalvans are follicular pustules, polytrichia, erosions and hemorrhagic crusts. At later stages dermal fibrosis predominates. The exact cause of folliculitis decalvans is not fully understood, but it is believed that Staphylococcus aureus may play a role in its development. Current knowledge regarding the pathogenesis of folliculitis decalvans suggests three stages including hyperactivation of innate immunity, bacterial infection and fibrosis as an outcome of the disease. The most frequently used treatments are topical steroids, topical antibiotics, and systemic antibacterial drugs, systemic isotretinoin, topical anti-inflammatory drugs, genetically engineered biological drugs, laser and surgical treatment, but all of the above methods usually result in only temporary remission. Phototherapy is an efficient therapy for a variety of skin diseases. We hypothesize that wavelengths in a range 308 nm eradicate bacteria more effectively than antibiotics in monotherapy. The combination of ultraviolet-B 308 nm, oral antibiotics, topical combined glucocorticoid drugs, topical and systemic application of bacteriophages, sensitives to the identified flora to the drugs have demonstrated an excellent tolerance and great outcomes in a series of cases.

Clinical characteristics and managements of severe corneal ulcers in patients with end-stage glaucoma.

To review the clinical characteristics and managements of severe corneal ulcers in patients with end-stage glaucoma. Retrospectively reviewed the medical records of patients diagnosed with severe corneal ulcers who had a history of end-stage glaucoma, including demographic profiles, medical histories, clinical features, and treatments. Thirty patients (30 eyes) were included. The median age at presentation was 73.00years (interquartile range [IQR]: 64.25-77.25years). The majority of patients were previously diagnosed with primary angle-closure glaucoma (11/30, 36.67%). Nineteen patients (63.33%) were still using antiglaucoma medications within 6 months before the onset of corneal ulcer. Visual acuity was already severely impaired in these patients before the onset of corneal ulcer. At last visit before the onset, 20 eyes (66.67%) had intraocular pressure (IOP) greater than 21mmHg. Corneal perforation occurred in 13 eyes (43.33%). Eleven eyes (36.67%) underwent debridement of corneal ulcer and conjunctival flap covering surgery, while 13 eyes (43.33%) eventually underwent evisceration. Patients without corneal perforation had received a greater variety of surgical or laser treatments in the past compared to those with corneal perforation (P = 0.047). A significantly larger proportion of patients with corneal perforation underwent evisceration (9/13 vs 4/17, P = 0.012). Severe corneal ulcers in patients with end-stage glaucoma were characterized by advanced age, long-term use of topical antiglaucoma medications and poor IOP control. Nearly half of the patients lost their eyes. Active treatment of underlying diseases and careful attention to ocular surface condition are crucial in preventing corneal perforation and improving prognosis.

Development and Characterization of Lornoxicam-Infused Ocular Gel for Effective Treatment of Ocular Inflammation in Domestic Cats

Lornoxicam (LOX) is a non-steroidal anti-inflammatory drug (NSAID) effective in managing ocular inflammation. Traditional delivery methods like liquid drops are cleared rapidly and may not provide sustained therapeutic levels, necessitating the development of an ocular gel formulation. Mucoadhesive polymers such as hyaluronic acid (HA), hydroxypropyl methylcellulose (HPMC), and Carbopol have been identified as suitable excipients to modify drug release profiles. This study aims to formulate an effective ophthalmic 0.1% w/w lornoxicam gel administered to pets for topical and continuous drug release, enhancing therapeutic efficacy while minimizing possible side effects. Eight formulations of lornoxicam ocular gel were developed by different concentrations of hyaluronic acid (HA) and hydroxypropyl methylcellulose (HPMC K100) with 0.5% w/v Carbopol P934. These formulations were in vitro evaluated for viscosity, spreadability, and drug release characteristics to the best formula G6. The formulation with optimal performance was G6 (0.5% w/v Hyaluronic acid). Ocular irritation testing was performed to assess the safety and tolerability of the formulation using a Rattus norvegicus Domestica (domestic Norwegian rat) model. Furthermore, the therapeutic potential of the lornoxicam gel was investigated in a domestic cat case study, demonstrating its efficacy in treating ocular inflammation resulting from traumatic eye injury. The optimized formula G6 formulation 0.5% w/v demonstrated appropriate viscosity and spreadability, making it suitable for ocular administration. In vitro release, studies revealed an initial burst release of 92.5% within the first two hours, followed by a sustained release over the subsequent 6 hours. Ocular irritation testing using a rat model confirmed that the lornoxicam ocular gel was non-irritating. Furthermore, the therapeutic effects of the gel were observed in domestic cats, with notable improvements in ocular conditions, including reduced swelling, redness, and dryness, for less than 7 days of treatment. The lornoxicam ocular gel demonstrates promising characteristics for safe and effective treatment of ocular inflammation in domestic cats‎‎‎.

Ethosomes in Transdermal and Topical Drug Delivery: A Review

The skin is one of the most extensive and readily accessible organs of the human body, and its use as a route for drug delivery offers numerous advantages over traditional drug delivery systems. These advantages include lower fluctuations in plasma drug levels, avoidance of gastrointestinal disturbances and first-pass metabolism, as well as improved patient compliance. Transdermal drug delivery systems (TDDS) are defined as self-contained, discrete dosage forms that, when applied to intact skin, deliver of drugs at the controlled rate to the systemic circulation Ethosomes, developed from Touitou et al. in 1997, are novel lipid carriers composed of ethanol, phospholipids and water. These ethosomes are designed as non-invasive drug carrier system that can permeate the skin, fuse with cell membrane lipids, and release the drug. Ethosomes can be formulated using either hot or cold methods. Evaluation parameters for ethosomes include size, shape, drug content and zeta potential. Ethosomes have been successfully evaluated for the delivery of various drugs, including cyclosporine a insulin and salbutamol. Overall, ethosomes hold great potential as an important drug delivery tool in the future.

Radiation Skin Injury: Cellular Mechanisms and Herbal & Alternative Treatment Approaches for Recovery

Nearly 90% of patients get moderate-to-severe skin reactions as a result of radiation therapy, making radiation-induced skin damage (RSI) a common side effect. This can hinder the treatment of their illness and drastically lower the quality of life for patients. There isn't yet a gold standard for treating RSIs, despite how common they are. In addition to discussing the pathophysiology of RSI, this article gives a summary of topical drugs that are used to treat it. In modern clinical medicine, it acts as a point of reference for clinicians to direct how they manage RSI. A serious side effect of several medical procedures, including radiation therapy for cancer, is RSI. Uncertainty surrounds the exact mechanisms underlying radiation-induced skin damage. Recent developments in cellular and molecular biology have uncovered a sophisticated web of pathways that contribute to the skin's radiation response. In this study, we go over the several processes and mechanisms that lead to radiation-induced skin damage, such as DNA damage, reactive oxygen species formation, inflammatory cytokine activation, and direct skin cell damage. We also go over how crucial it is to comprehend these pathways in order to create treatment plans that lessen radiation-induced skin damage. We also look at herbal remedies as possible complementary or alternative treatments for RSI, emphasising how they might aid in skin restoration and promote healing. In order to manage RSI more effectively, this review aims to support doctors in combining conventional and herbal therapeutic alternatives in a complete strategy.

Evaluation of Visual, Refractive, and Functional Outcomes after Implantation of an Extended Depth of Focus Intraocular Lens in Patients with Stable and Mild Glaucoma.

The aim of this study is to describe the visual, refractive, functional, and patients' satisfaction outcomes of the AcrySof™ IQ Vivity™ extended depth-of-focus intraocular lens (EDOF IOL) in patients with mild primary open-angle glaucoma (POAG). This is an ambispective, multicenter, and descriptive study. Patients with mild and stable POAG for at least 6months, as well as patients who had the AcrySof™ IQ Vivity™ EDOF IOL implanted were included. Humphrey Field Analyzer III (Carl Zeiss Meditec, Dublin, CA, USA) and Triton optical coherence tomography (Topcon, Japan) were used to evaluate the inclusion criteria. In all cases, the formula used to calculate IOL power was Barrett Universal II. Refractive outcomes and visual acuity at distance, intermediate, and near were evaluated from 3months postoperatively onward. In addition, monocular and binocular defocus curve and contrast sensitivity (CSV-1000, VectorVision, Greenvile, OH, USA) were assessed. Patient satisfaction was assessed through the Intraocular Lens Satisfaction (IOLSAT) and Questionnaire for Visual Disturbances (QUVID) questionnaires . In total, 72 AcrySof™ IQ Vivity™ lenses from 36 patients were enrolled, of which 28 were women. The mean age was 71.61 ± 7.68years, the mean thickness of the retinal nerve fiber layer (RNFL) was 79.24 ± 14.96µm, the mean intraocular pressure (IOP) was 16.88 ± 3.09mmHg, and the mean number of topical anti-glaucoma medication was 0.89 ± 0.95. Binocular corrected distance visual acuity (CDVA), binocular corrected intermediate visual acuity (CIVA), and binocular corrected near visual acuity (CNVA) were 0.00 ± 0.12, 0.16 ± 0.14, and 0.24 ± 0.11 LogMAR, respectively. Spherical equivalent was -0.27 ± 0.33 diopters (D). In addition, 86.11% of eyes were within ± 0.5D and 95.83% were within ± 1.0D. The binocular defocus curve shows a peak of maximum visual acuity (VA) at 0D (0.00 ± 0.11 LogMAR) and smooth curve at intermediate (66cm/-1.5D) 0.11 ± 0.09 LogMAR and near distance (40cm/-2.5D) 0.36 ± 0.18 LogMAR. Binocular contrast sensitivity showed a decrease in high spatial frequencies compared with low spatial frequencies. The IOLSAT revealed that in bright light conditions, 88.89%, 91.67%, and 63.89% of patients "never" or "rarely" need glasses at far, arm's length, and near distances, respectively. In addition, according to the QUVID, 97.06% of patients "never" report shadow areas. The new AcrySof™ IQ Vivity™ EDOF IOL seems to provide good visual outcomes at distance, intermediate, and near vision, with an adequate contrast sensitivity, defocus curve, a low rate of visual disturbances and high visual satisfaction in patients with mild and stable POAG.

Quantitative evaluation of trabecular meshwork in normal tension glaucoma using trabecular meshwork analyzing software.

Quantitative evaluation of trabecular meshwork in normal tension glaucoma using trabecular meshwork analyzing software.

Chemical composition of the traditional Chinese medicine compound (ICAM), its antifungal effects against Candida albicans, and the underlying Mechanisms: Therapeutic potential and safety evaluation for vulvovaginal candidiasis.

Chemical composition of the traditional Chinese medicine compound (ICAM), its antifungal effects against Candida albicans, and the underlying Mechanisms: Therapeutic potential and safety evaluation for vulvovaginal candidiasis.

Randomized Non-Inferiority Trial of Direct Selective Laser Trabeculoplasty in Open-Angle Glaucoma and Ocular Hypertension: GLAUrious.

Randomized Non-Inferiority Trial of Direct Selective Laser Trabeculoplasty in Open-Angle Glaucoma and Ocular Hypertension: GLAUrious.

Investigation of the participation of the TRPV1 receptor in the irritant effect of dithranol in mice.

Investigation of the participation of the TRPV1 receptor in the irritant effect of dithranol in mice.

Investigation of the Suitability of Utilizing Plasma Concentration as a Surrogate to Understand Lung Exposure of Inhaled Drug in Rats: Different Delivery Methods of Fluticasone Propionate.

Investigation of the Suitability of Utilizing Plasma Concentration as a Surrogate to Understand Lung Exposure of Inhaled Drug in Rats: Different Delivery Methods of Fluticasone Propionate.

Photobimodulation therapy with topical drug treatment (glutamine and hyaluronic acid) for the control of oral mucositis

Photobimodulation therapy with topical drug treatment (glutamine and hyaluronic acid) for the control of oral mucositis

Wound Healing Properties of Plant-Based Hydrogel and Oleogel Formulations in a Rat Scald Burn Model

Background: Scald burns pose significant morbidity, and effective topical treatments remain a clinical priority. Burn injuries pose a significant clinical challenge due to the prolonged inflammation and high infection risk. Traditional treatments focus on moisture retention and infection prevention, but biocompatible formulations such as hydrogels and oleogels offer advantages. Hydrogels hydrate, cool, and promote epidermal regeneration, while oleogels form a lipid barrier that enhances the absorption of lipophilic bioactive compounds. There is an increasing demand for novel topical alternatives that can effectively improve wound healing by modulating the inflammatory cascade, accelerating epithelial and dermal regeneration, and restoring barrier function. Objective: This study aimed to determine the most effective plant-based topical formulations for enhancing second-degree scald burn wound healing. Methods: Utilizing a standardized rat model, we compared 21 distinct topical formulations, consisting of oleogel and hydrogel bases enriched with extracts from Boswellia serrata (frankincense), Ocimum basilicum (basil), Sambucus nigra flower (elderflower), and Galium verum (lady’s bedstraw). Second-degree burns were uniformly induced in 24 Wistar rats using boiling water (100 °C for 8 s) using the RAPID-3D device, a validated 3D-printed tool that ensures reproducible burns through controlled exposure to boiling water. Post-burn, rats were divided into three equal subgroups, and topical formulations were applied daily. Wound healing efficacy was evaluated through wound surface area measurements, transepidermal water loss (TEWL), skin hydration, sebum production, pigmentation, inflammation (erythema), skin perfusion, and histological parameters at multiple timepoints (days 1, 4, 9, 14, and 21 post-burn induction). Results: Statistical analyses indicated significant advantages of oleogel-based formulations over hydrogel-based formulations. Specifically, formulations containing Boswellia serrata and Ocimum basilicum extracts significantly reduced wound size and inflammation, improved skin hydration, and decreased melanin production by days 9 and 21 (p < 0.05). Conclusions: These findings underscore the potential clinical value of oleogel-based topical preparations containing specific plant extracts for improving scald burn wound healing outcomes, warranting further clinical evaluation.

A Randomized Phase 1 Study Evaluating Pharmacokinetics, Safety, and Tolerability of a High-Concentration, Long-Acting Cabotegravir Formulation in Adults Without HIV.

Long-acting (LA) cabotegravir 200-mg/mL (CAB200) injections are approved for HIV-1 prevention and as a complete LA HIV-1 treatment regimen with rilpivirine. A high-concentration suspension formulation, cabotegravir 400mg/mL (CAB400-D), was developed to enable less frequent dosing and self-administration. This phase 1, double-blind, randomized study (NCT04484337) evaluated intramuscular (IM) gluteal, subcutaneous (SC) abdominal, and IM thigh CAB400-D injections (200-800mg [0.5-2.0mL]) in adults without HIV, using CAB200 injections as active control. Co-administration with recombinant human hyaluronidase (rHuPH20), topical nonsteroidal anti-inflammatory drug, or topical steroid was evaluated for some SC injections. Pharmacokinetics, adverse events (AEs), and participant-reported outcomes were assessed. Overall, 138 participants were enrolled. Absorption was faster with CAB400-D versus CAB200. Within 4 weeks, CAB400-D plasma exposures were similar across administration routes and higher than those of CAB200. Co-administration with rHuPH20 increased the spontaneous absorption rate of CAB400-D but not CAB200. No deaths or drug-related serious AEs were observed. Five (4%) participants discontinued treatment due to AEs (injection-site reactions [ISRs], n=3 discontinuations). Most (99%) participants experienced ≥1 ISR. Participants reported good acceptability of injections. Although CAB400-D injections demonstrated acceptable safety/tolerability, faster absorption than CAB200 limited potential dosing intervals to monthly dosing. Alternative cabotegravir formulations with longer dosing intervals are under clinical evaluation.

Basic therapy for chronic non-infectious dermatoses of the anogenital region

Chronic non-infectious dermatoses of the anogenital area comprise a heterogeneous group of diseases characterized by varied etiopathogenesis, clinical manifestations, disease course, and prognosis. Treatment of dermatological conditions in the anogenital area often presents a complex challenge and necessitates an interdisciplinary approach. Traditionally, comprehensive therapy is employed, including agents aimed at restoring the cutaneous barrier, topical anti-inflammatory medications, particularly glucocorticosteroids and/or topical calcineurin inhibitors, and less frequently, systemic glucocorticosteroids, retinoids, hydroxychloroquine, or dapsone, as well as interventions targeting the alleviation of subjective symptoms and the prevention and treatment of secondary infections. The purpose of this publication is to discuss the fundamental aspects of baseline therapy for chronic non-infectious dermatoses of anogenital area. Baseline therapy is defined as a set of interventions that a patient with a dermatosis receives over a prolonged or continuous period, even during disease remission. Approaches to baseline therapy for dermatoses of anogenital area are poorly developed and require further clarification. Nevertheless, the regulation of the spectrum and quantity of agents used by the patient on the genital and perianal areas, the elimination of irritants, normalization of daily hygiene practices, and the use of agents that restore the cutaneous barrier are crucial components of comprehensive therapy for skin diseases in this anatomical location. One of the key aspects of successful treatment of dermatoses of anogenital area is the restoration of the cutaneous barrier, which can be disrupted by both the underlying disease processes and exposure to external factors. This article details the effects of preparations based on 5% dexpanthenol, which is regarded as a moisturizing and wound-healing agent. Dexpanthenol demonstrates significant anti-inflammatory activity, comparable to that of corticosteroids. Its use in therapy not only improves skin condition but also enhances the efficacy of cjrticosteroids, which is particularly important for patients requiring long-term management of dermatoses.

Green Hydrogels Prepared from Pectin Extracted from Orange Peels as a Potential Carrier for Dermal Delivery Systems.

Recycling fruit waste, like orange peels, into a green, eco-friendly, low-cost, and sustainable product is an effective way to reduce fruit waste. Pectin is a natural polymer extracted from citrus peels. It is widely utilized as a gelling agent, stabilizer, thickener, emulsifier, and rheology modifier. This study aimed to develop green gels from pectin extracted from orange peels as a carrier for topical preparations. The extracted pectin was characterized by a yield% of 14%, a degree of esterification of 20%, an equivalent weight of 2500 g/mol, a methoxyl content of 14.88%, and a galacturonic acid content of 91.52%. Additionally, the ethanolic orange peel extract was also prepared and compared with pectin hydrogels. Hydrogels were prepared using 8, 16, and 32% pectin concentrations, cross-linked with 0, 20, 40, 60, and 80% CaCl2 concentrations, while the pH of the hydrogel was adjusted to 3.5 and 8.5. Pectin hydrogels exhibited pseudoplastic behavior, viscoelastic properties with elastic modulus G' dominating the viscous modulus G″, and bioadhesive properties. Moreover, the aqueous and ethanolic extractions of pectin from orange peels demonstrated a concentration-dependent antioxidant activity. Pectin hydrogels did not demonstrate wound healing or antimicrobial activities. In contrast, the ethanolic orange peel extract demonstrated improved wound healing, antimicrobial activity against the Gram-positive bacteria Staphylococcus aureus, and antioxidant activity. Therefore, the pectin hydrogel could serve as a potential carrier for dermal delivery systems. Moreover, the ethanolic orange peel extract has demonstrated potential as a dermal drug delivery carrier in wound healing and antimicrobial and antioxidant agents.

Prevalence of Common Contact Allergens in Topical Diaper Preparations for Infants.

In cases of persistent perineal dermatitis (PD), allergic contact dermatitis should be considered and common potential allergens avoided in topical diaper preparations. Our study reviewed the best-selling diaper preparations on a popular website to identify the number and types of allergens in each product, based on the 2018 Pediatric Baseline Patch Test Series and North American Contact Dermatitis Group-70. Of the products reviewed, 21/25 (84%) percent contained one or more potential allergens. Additionally, we provide a list of products that do not have ingredients contained on either potential allergen list.

Clinical Outcomes of Infected Corneal Ulcers in Dogs With or Without the Use of Topical Serum.

To determine if topical serum use impacts clinical outcomes of infected corneal ulcers in dogs. A total of 252 eyes (237 dogs) undergoing medical and surgical therapy for infected corneal ulcers managed with or without topical serum. Patients were identified retrospectively in the same geographic region of the United States. Healing times, visual outcomes, and enucleation were recorded for medically managed ulcers. Visual outcomes and enucleation were recorded for surgically managed ulcers. The number and frequency of topical medications were recorded for all groups. Statistical analyses were performed for all comparisons, with a significance level of p = 0.05. In total, 252 eyes (237 dogs) were included. Of these, 203 eyes underwent medical therapy (150 without serum/53 with serum) and 49 eyes were treated surgically at presentation (35 without serum/14 with serum postoperatively). In the medical group, the use of serum had no impact on healing times (p = 0.380), visual outcomes (p = 0.751) or enucleation (p = 0.433). In the surgery group, visual outcomes (p = 0.488) and enucleation (no eyes enucleated) were not impacted by serum use. Healing times were not impacted by frequency (p = 0.092) or number of topical medications (p = 0.346). To the authors' knowledge, this is the first study to determine if topical serum use affects clinical outcomes of infected corneal ulcers in dogs. Topical serum did not impact healing times, visual outcomes, or enucleation rates of infected corneal ulcers treated medically or surgically in dogs.