Gamma-mangostin Protects S16Y Schwann Cells Against tert-Butyl Hydroperoxide-induced Apoptotic Cell Death.

BACKGROUND: Peripheral neuropathy is a common complication that affects individuals with diabetes. Its development involves an excessive presence of oxidative stress, which leads to cellular damage in various tissues. Schwann cells, which are vital for peripheral nerve conduction, are particularly susceptible to oxidative damage, resulting in cell death. MATERIALS AND METHODS: Gamma-mangostin (γ-mangostin), a xanthone derived from Garcinia mangostana, possesses cytoprotective properties in various pathological conditions. In this study, we employed S16Y cells as a representative Schwann cell model to investigate the protective effects of γ-mangostin against the toxicity induced by tert-Butyl hydroperoxide (tBHP). Different concentrations of γ-mangostin and tBHP were used to determine non-toxic doses of γ-mangostin and toxic doses of tBHP for subsequent experiments. MTT cell viability assays, cell flow cytometry, and western blot analysis were used for evaluating the protective effects of γ-mangostin. RESULTS: The results indicated that tBHP (50 µM) significantly reduced S16Y cell viability and induced apoptotic cell death by upregulating cleaved caspase-3 and cleaved PARP protein levels and reducing the Bcl- XL/Bax ratio. Notably, pretreatment with γ-mangostin (2.5 µM) significantly mitigated the decrease in cell viability caused by tBHP treatment. Furthermore, γ-mangostin effectively reduced cellular apoptosis induced by tBHP. Lastly, γ-mangostin significantly reverted tBHP-mediated caspase-3 and PARP cleavage and increased the Bcl-XL/Bax ratio. CONCLUSION: Collectively, these findings highlight the ability of γ-mangostin to protect Schwann cells from apoptotic cell death induced by oxidative stress.

Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers.

An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 µg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential biological risks. Intranasal NAS administration in rats showed no circulatory presence of human IgG1 anti-SARS-CoV-2 antibodies within 120 h. A double-blind, randomized, placebo-controlled trial (NCT05358873) was conducted on 36 healthy volunteers who received either NAS or a normal saline nasal spray. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. NAS was well tolerated, with no significant adverse effects during the 14 days of the study. The SARS-CoV-2 neutralizing antibodies were detected based on the signal inhibition percent (SIP) in nasal fluids pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SIP values in nasal fluids collected immediately or 6 h after NAS application were significantly increased from baseline for all three variants tested, including ancestral, Delta, and Omicron BA.2. In conclusion, NAS was safe for intranasal use in humans to increase neutralizing antibodies in nasal fluids that lasted at least 6 h.

Mussel-inspired poly(hydroxyethyl acrylate-co-itaconic acid)-catechol/hyaluronic acid drug-in-adhesive patches for transdermal delivery of ketoprofen.

This research aimed to create new hydrophilic drug-in-adhesive patches for transdermal drug delivery. Poly(hydroxyethyl acrylate-co-itaconic acid)-catechol (PHI-cat) and hyaluronic acid (HA) were used as main components in the pressure-sensitive adhesive. Citric acid and aluminium hydroxide were exploited as crosslinking agents and ketoprofen was employed as a model delivering compound. The adhesive performance, physicochemical properties, drug-polymer interaction, drug crystallization, drug content, drug permeation through the skin, and coordination polymer network of the patches were investigated. In addition, skin irritation and adhesion potential in human subjects were assessed. Due to the ability of catechol groups to form interaction with the skin tissue, the patches containing PHI-cat and HA offered a considerably greater adhesion ability to human skin compared with the patches without catechol and commercial patches. Furthermore, the patches had good physical and chemical stability. Therefore, these catechol-functionalized patches may be potential transdermal drug delivery systems with excellent adhesive properties for the delivery of a drug through the skin.

Bioinspired ketoprofen-incorporated polyvinylpyrrolidone/polyallylamine/ polydopamine hydrophilic pressure-sensitive adhesives patches with improved adhesive performance for transdermal drug delivery.

Inspired by the natural mussel adhesive mechanism, three different materials-polydopamine (PDA), polyvinylpyrrolidone (PVP), and polyallylamine (PAM)-were used to make innovative pressure-sensitive adhesives (PSAs) for transdermal delivery of ketoprofen. PDA was synthesized under alkaline conditions using a self-polymerization reaction and was exploited as a cross-linking agent due to its biocompatibility. The adhesive performance, physicochemical properties, drug content, and drug permeation through the skin were examined. Moreover, in vivo skin irritation and skin adhesion performance were investigated. PVP/PAM/PDA PSAs showed a significantly higher adhesion to human skin compared with commercial patches owing to the interaction between the catechol groups presented on the patches and the skin. In addition, the patches were stable for six months. Consequently, the PVP/PAM/PDA patches exhibited outstanding tissue adhesiveness, enabling universal tissue adherence while causing no skin tissue irritation or inflammatory reaction.

Nanostructured lipid carrier-embedded polyacrylic acid transdermal patches for improved transdermal delivery of capsaicin.

Capsaicin has been used as a topical treatment for skeletomuscular and neuropathic pain. However, it has some side effects when it is applied to the skin such as burning, erythema, and skin irritation resulting in poor patient compliance. These adverse effects are caused by the rapid penetration of capsaicin into the outer layer of the epidermis and low permeation to the dermis layer. This study aimed to develop nanostructured lipid carriers (NLCs) embedded transdermal patches for improved transdermal delivery of capsaicin. An optimum formulation of NLCs (0.3% capsaicin) with a particulate size smaller than 200 nm, narrow size distribution, and acceptable colloidal stability was used for preparing transdermal patches. Polyacrylic acid (7%) was employed as the polymer base of the transdermal patches as it provided high adhesive performance and a sustained release of capsaicin. Moreover, the patches containing capsaicin-loaded NLCs could offer a higher deposition of capsaicin in the deeper layer of the skin compared to the conventional capsaicin patches. In vivo skin irritation studies indicated that the conventional capsaicin patches can cause skin irritation and redness, whereas capsaicin NLCs-loaded patches exhibited lower skin side effects. Therefore, the capsaicin NLCs-loaded patches could be a potential delivery system of capsaicin through the skin with possibly reduced skin irritation.

Development and Evaluation of Novel Water-Based Drug-in-Adhesive Patches for the Transdermal Delivery of Ketoprofen.

The objective of this study was to develop novel water-based drug-in-adhesive pressure-sensitive adhesives (PSAs) patches for the transdermal delivery of ketoprofen, employing poly(N-vinylpyrrolidone-co-acrylic acid) copolymer (PVPAA) and poly(methyl vinyl ether-alt-maleic anhydride) (PMVEMA) as the main components. The polymers were crosslinked with tartaric acid and dihydroxyaluminium aminoacetate using various polymer ratios. Ketoprofen was incorporated into the PVPAA/PMVEMA PSAs during the patch preparation. The physicochemical properties, adhesive properties, drug content, release profile, and skin permeation of the patches were examined. Moreover, the in vivo skin irritation and skin adhesion performance in human volunteers were evaluated. The patches prepared at a weight ratio of PVPAA/PMVEMA of 1:1 presented the highest tacking strength, with desirable peeling characteristics. The ketoprofen-loaded PVPAA/PMVEMA patches exhibited superior adhesive properties, compared to the commercial patches, because the former showed an appropriate crosslinking and hydrating status with the aid of a metal coordination complex. Besides, the permeated flux of ketoprofen through the porcine skin of the ketoprofen-loaded PVPAA/PMVEMA patches (4.77 ± 1.00 µg/cm2/h) was comparable to that of the commercial patch (4.33 ± 0.80 µg/cm2/h). In human studies, the PVPAA/PMVEMA patches exhibited a better skin adhesion performance, compared with the commercial patches, without skin irritation. In addition, the patches were stable for 6 months. Therefore, these novel water-based PSAs may be a potential adhesive for preparing drug-in-adhesive patches.