Prednisolone and dexamethasone are systemically absorbed after topical application of ophthalmic suspensions in healthy dogs

OBJECTIVE To quantify plasma concentrations of prednisolone and dexamethasone (peripheral and jugular) and cortisol following topical ophthalmic application of 1% prednisolone acetate and 0.1% dexamethasone to healthy adult dogs. ANIMALS 12 purpose-bred Beagles. PROCEDURES Dogs received 1 drop of 1% prednisolone acetate (n = 6) or neomycin polymyxin B dexamethasone (ie, 0.1% dexamethasone; 6) ophthalmic suspension in both eyes every 6 hours for 14 days. Blood samples (peripheral and jugular) were collected on days 0, 1, 7, and 14 and analyzed for plasma prednisolone and dexamethasone concentrations. Plasma cortisol concentrations were measured at the beginning of the study and following topical drug administration. RESULTS Both drugs demonstrated systemic absorption. Prednisolone was detected on days 1, 7, and 14 (median plasma concentration, 24.80 ng/mL; range, 6.20 to 74.00 ng/mL), and dexamethasone was detected on days 1, 7, and 14 (2.30 ng/mL; 0 to 17.70 ng/mL). Neither prednisolone nor dexamethasone were detected in plasma samples on day 0 (baseline). Sampling from the jugular vein resulted in higher plasma drug concentrations than from a peripheral vein when samples from each day were combined. Plasma cortisol concentrations were significantly lower than baseline following 14 days of treatment with topical prednisolone acetate and dexamethasone. CLINICAL RELEVANCE Prednisolone and dexamethasone are detected in the plasma of healthy dogs following topical ophthalmic administration 4 times/d with prednisolone concentrations being close to a physiologic dose of orally administered prednisolone. Additional research is needed to evaluate the systemic absorption of these medications in dogs with ocular inflammation.

Egg-derived anti-SARS-CoV-2 immunoglobulin Y (IgY) with broad variant activity as intranasal prophylaxis against COVID-19: preclinical studies and randomized controlled phase 1 clinical trial

COVID-19 emergency use authorizations and approvals for vaccines were achieved in record time. However, there remains a need to develop additional safe, effective, easy-to-produce, and inexpensive prevention to reduce the risk of acquiring SARS-CoV-2 infection. This need is due to difficulties in vaccine manufacturing and distribution, vaccine hesitancy, and, critically, the increased prevalence of SARS-CoV-2 variants with greater contagiousness or reduced sensitivity to immunity. Antibodies from eggs of hens (immunoglobulin Y; IgY) that were administered receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were developed as nasal drops to capture the virus on the nasal mucosa. Although initially raised against the 2019 novel coronavirus index strain (2019-nCoV), these anti-SARS-CoV-2 RBD IgY surprisingly had indistinguishable enzyme-linked immunosorbent assay binding against variants of concern that have emerged, including Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529). This is distinct for sera from immunized or convalescent patients. Culture neutralization titers against available Alpha, Beta, and Delta were also indistinguishable from the index SARS-CoV-2 strain. Efforts to develop these IgY for clinical use demonstrated that the intranasal anti-SARS-CoV-2 RBD IgY preparation showed no binding (cross-reactivity) to a variety of human tissues and had an excellent safety profile in rats following 28-day intranasal delivery of the formulated IgY. A double-blind, randomized, placebo-controlled phase 1 study evaluating single-ascending and multiple doses of anti-SARS-CoV-2 RBD IgY administered intranasally for 14 days in 48 healthy participants also demonstrated an excellent safety and tolerability profile, and no evidence of systemic absorption. As these antiviral IgY have broad selectivity against many variants of concern, are fast to produce, and are a low-cost product, their use as prophylaxis to reduce SARS-CoV-2 viral transmission warrants further evaluation.

The tale of microencapsulated rifampicin: is it useful for the treatment of periprosthetic joint infection?

Purpose Microencapsulation techniques have allowed the addition of rifampicin to bone cement, but its in vivo efficacy has not been proven. The aim of our study is to determine the superiority of cement containing gentamicin and rifampicin microcapsules in the treatment of PJI versus cement exclusively containing gentamicin. Methods An S. aureus PJI was induced in 15 NZW rabbits. A week after inoculation, the first stage of replacement was carried out, and the animals were divided into two groups: group R received a spacer containing gentamicin and rifampicin microcapsules, and group C received a spacer containing gentamicin. Intra-articular release curve of rifampicin and infection and toxicity markers were monitored for four weeks post-operatively, when microbiological analysis was performed. Results The microbiological cultures showed a significantly lower growth of S. aureus in soft tissue (2.3·104 vs 0; p = 0.01) and bone (5.7·102 vs 0; p = 0.03) in the group with rifampicin microcapsules. No differences were found in systemic toxicity markers. Rifampicin release from the cement spacer showed higher concentrations than the staphylococcal MIC throughout the analysis. Conclusion The in vivo analyses demonstrated the superiority of cement containing gentamicin and rifampicin microcapsules versus the isolated use of gentamicin in the treatment of PJI in the rabbit model without serious side effects due to the systemic absorption of rifampicin. Given the increasing incidence of staphylococci-related PJI, the development of new strategies for intra-articular administration of rifampicin for its treatment has a high clinical impact.

Treatment with clobetasol propionate 0.025% topical therapy in various dermatoses

Owing to their anti-inflammatory and vasoconstrictive properties. Topical corticosteroids (TCs) provide benefits in various dermatological conditions, including atopic eczema, psoriasis, chronic hand eczema, and localized vitiligo. Clobetasol propionate (CP) is the most common topical agent possessing anti-inflammatory, antimitotic, antipruritic, and immunosuppressive properties that are employed in the management of plaque psoriasis. CP 0.025% cream was approved by the United States food and drug administration for the treatment of moderate-to-severe psoriasis in adult patients. The formulation is free from known contact allergens, such as propylene glycol, short-chain alcohols, and sorbitol-based emulsifiers, and has demonstrated hypoallergenic effects. High penetration of active ingredients and a lower degree of systemic absorption make CP 0.025% an effective and safe agent. This case series discusses the clinical experience of using CP 0.025% cream in various dermatologic conditions, focusing on its efficacy and safety.

New Strategies for Improving Budesonide Skin Retention

The aim of this work was to evaluate the ex vivo effect of the combination of two strategies, complexation with cyclodextrin, and poloxamer hydrogels, for improving water solubility in the dermal absorption of budesonide. Two hydrogels containing 20% poloxamer 407, alone or in combination with poloxamer 403, were prepared. Each formulation was loaded with 0.05% budesonide, using either pure budesonide or its inclusion complex with hydroxypropyl-β-cyclodextrin, and applied in finite dose conditions on porcine skin. The obtained results showed that for all formulations, budesonide accumulated preferentially in the epidermis compared to the dermis. The quantity of budesonide recovered in the receptor compartment was, in all cases, lower than the LOQ of the analytical method, suggesting the absence of possible systemic absorption. The use of a binary poloxamer mixture reduced skin retention, in line with the lower release from the vehicle. When the hydrogels were formulated with the inclusion complex, an increase in budesonide skin retention was observed with both hydrogels. Poloxamer hydrogel proved to be a suitable vehicle for cutaneous administration of budesonide.

Phase 1/2 Study of Topical Submicron Particle Paclitaxel for Cutaneous Metastases of Breast Cancer

Purpose: This Phase 1/2 study evaluated safety and efficacy of a topical submicron particle paclitaxel (SPP) in an anhydrous ointment base (SOR007), primarily in breast cancer patients with cutaneous metastases (CM).Methods: One of 3 concentrations of SOR007 SPP (0.15%, 1.0%, or 2.0%) was applied twice daily over an area of 50 cm2 under a 3+3 phase I design for up to 28 days, with the option for additional 28 days at the highest dose once safety was established. Efficacy was analyzed by lesion measurements and photographs to determine overall response rate (ORR), complete response (CR) and progression free survival by day 28 or 56.Results: Twenty-three subjects were enrolled, 21 with cutaneous metastases of breast cancer (CMOBC). Four subjects received SOR007 0.15%, three at a dose of 1.0% for a median of 28 days (range = 6 to 29 days), and sixteen at 2.0% for a median of 56 days (range = 42 to 60). All doses were well tolerated, and 19 subjects were evaluable for efficacy. At day 28 across all dose levels, 16% (95%CI: 3.4 to 39.6%) of subjects achieved an ORR and another 63.1% (95%CI: 34.9 to 96.8%) had stable disease (SD). The proportion of patients being progression free at 28 days across all treatments was 79% (95:CI: 54 to 94%). Conclusion: Application of SOR007 0.15%, 1.0%, and 2.0% to CM resulted in lesion stabilization or response in most subjects, with reduced lesion pain, and minimal systemic absorption of paclitaxel. A randomized, placebo-controlled trial to confirm these findings is warranted.NCT: #03101358

Nefecon (targeted-release formulation-budesonide) for the treatment of IgA nephropathy

Budesonide is a second-generation synthetic, nonhalogenated corticosteroid; it acts locally with minimal systemic absorption. The oral formulation Nefecon® is under clinical development from the treatment of IgA nephropathy. Thanks to its specific formulation, it could inhibit the pathogenetic process of IgA nephropathy at its source while avoiding the toxicity of systemic glucocorticoids. A Phase II clinical trial has shown a statistically significant antiproteinuric effect of budesonide on top of therapy with inhibitors of the renin–angiotensin system, with a good safety profile. More recently, preliminary results of a larger, Phase III clinical trial have confirmed the antiproteinuric efficacy of oral budesonide. These findings were submitted to the US FDA and the EMA to undergo fast revision and approval for clinical use.

Niosomes: A Promising Drug Delivery System in Transdermal Drug Delivery (TDDS)

Infectious disease treatment and immunisation have undergone a transformative change in recent years. With the advancement of biotechnology and genetic engineering, a large number of disease-specific biological have been created, as well as a focus on delivering these biological effectively. Niosomes are vesicular Nano carriers that are gaining popularity as a potential transdermal drug delivery system due to properties like enhanced drug penetration, a local depot for sustained drug release, and a rate-limiting membrane for modulating systemic absorption of drugs through the skin. Niosomes are non-ionic surfactant-based vesicles that are biodegradable, relatively nontoxic, more stable, and less expensive than liposomes. This analysis gives a high-level overview of niosomes, including their chemical composition, structure, benefits, and applications, as well as some general observations on niosomes as percutaneous permeation enhancers.

The Beneficial Effect of Rosmarinic Acid on Benzophenone-3-Induced Alterations in Human Skin Fibroblasts

Benzophenone-3 (BP-3) is one of the most widely used chemical sunscreens. The results of many in vitro and in vivo tests confirm its high percutaneous penetration and systemic absorption, which question the safety of its wide use. The aim of our research was to assess the effect of this compound on components of the skin extracellular matrix, and to investigate whether rosmarinic acid (RA) could reduce BP-3-induced changes in human skin fibroblasts. BP-3 used at concentrations of 0.1–100 µM caused a number of unfavorable changes in the level of type I collagen, decorin, sulfated glycosaminoglycans, hyaluronic acid, elastin, and expression or activity of matrix metalloproteinases (MMP-1, MMP-2), elastase and hyaluronidase. Moreover, the intracellular retention of collagen was accompanied by changes in the expression of proteins modifying and controlling the synthesis and secretion of this protein. Most importantly, RA at a concentration of 100 µM significantly reduced or completely abolished the adverse effects of BP-3. Based on these findings, it can be concluded that this polyphenol may provide effective protection against BP-3-induced disturbances in skin cells, which may have important clinical implications.