Cyclodextrins and Amino Acids Enhance Solubility and Tolerability of Retinoic Acid/Tretinoin: Molecular Docking, Physicochemical, Cytotoxicity, Scratch Assay, and Topical Gel Formulations Investigation.

With increasing longevity globally, the search for effective and patient-friendly anti-aging solutions has been growing. Retinoic acid (Ret) is an FDA-approved anti-aging and anti-wrinkling formula, however, its poor solubility and poor tolerability hamper its use in cosmetically accepted formulations. In this study, cyclodextrins and arginine were investigated for improving the solubility and tolerability of retinoic acid through the formation of inclusion complexes and salt formation, respectively. Two different methods were employed: physical mixing and kneading. The prepared dispersions were investigated for molecular docking (MD), solubility, thermal and spectral analyses, cytotoxicity, and scratch assays. The optimized disperse systems were formulated in a gel formulation and characterized for rheological, in vitro release, and kinetics. The MD, DSC, and FTIR results indicated that both ß- and hydroxy propyl (HP) ß-cyclodextrins could host RA in their cavities and form inclusion complexes. Ret can form a salt with the basic amino acid arginine. Solubility studies of RA significantly (p < 0.01) enhanced by 14- to 81-fold increases with the investigated cyclodextrins and arginine. The cell viability recorded for Ret:HP ß-CD K and Ret:arginine K was significantly increased compared to that for Ret alone. The IC50% recorded for azelaic acid (mild to non-irritant control), Ret, Ret:HP ß-CD K, and Ret:arginine K were 1000, 485, 1100, and 895 µg/mL, respectively. The two carriers (HP ß-CD and the amino acid arginine) were able to significantly (p < 0.05) reduce the irritation potential of Ret. Furthermore, comparable gap closure rates were recorded for Ret alone, Ret:HP ß-CD K, and Ret:arginine K, indicating that inclusion complexation and ion pair formation reduced the irritation potentials without undermining the efficacy.

Unravelling the in vivo dynamics of liposomes: Insights into biodistribution and cellular membrane interactions.

Liposomes, as a colloidal drug delivery system dating back to the 1960s, remain a focal point of extensive research and stand as a highly efficient drug delivery method. The amalgamation of technological and biological advancements has propelled their evolution, elevating them to their current status. The key attributes of biodegradability and biocompatibility have been instrumental in driving substantial progress in liposome development. Demonstrating a remarkable ability to surmount barriers in drug absorption, enhance stability, and achieve targeted distribution within the body, liposomes have become pivotal in pharmaceutical research. In this comprehensive review, we delve into the intricate details of liposomal drug delivery systems, focusing specifically on their pharmacokinetics and cell membrane interactions via fusion, lipid exchange, endocytosis etc. Emphasizing the nuanced impact of various liposomal characteristics, we explore factors such as lipid composition, particle size, surface modifications, charge, dosage, and administration routes. By dissecting the multifaceted interactions between liposomes and biological barriers, including the reticuloendothelial system (RES), opsonization, enhanced permeability and retention (EPR) effect, ATP-binding cassette (ABC) phenomenon, and Complement Activation-Related Pseudoallergy (CARPA) effect, we provide a deeper understanding of liposomal behaviour in vivo. Furthermore, this review addresses the intricate challenges associated with translating liposomal technology into practical applications, offering insights into overcoming these hurdles. Additionally, we provide a comprehensive analysis of the clinical adoption and patent landscape of liposomes across diverse biomedical domains, shedding light on their potential implications for future research and therapeutic developments.

Non-invasive caffeinated-nanovesicles as adipocytes-targeted therapy for cellulite and localized fats.

Caffeine (CAF) is a non-selective adenosine A1 receptor antagonist which predominates in fat cells. When CAF binds to adenosine receptors, it increases cyclic adenosine monophosphate; inhibiting adipogenesis and inducing fat lipolysis. Resveratrol (RSV) is an antioxidant polyphenol possessing different anti-obesity mechanisms. Topical application of both hydrophilic CAF and lipophilic RSV is limited. This study aimed to develop novel caffeinated-resveratrol bilosomes (CRB) and caffeine-bilosomes (CB) that could non-invasively target and deposit in fat cells. RSV bilosomes (RB) were prepared as a non-targeted system for comparison. CRB showed nanosize (364.1 nm ±6.5 nm) and high entrapment for both active compounds. Rats treated topically with CRB revealed a significant decrease (P = 0.039) in body weight. Histological analysis of the excised skin demonstrated a reduction in the subcutaneous fatty layer thickness and a decrease in the size of connective tissue-imbedded fat cells. Kidney histological examination of RB-treated rats showed subcapsular tubular epithelial cells with cytoplasmic vacuolation. This reflects a systemic effect of RSV from the non-targeted RB compared to CRB, which had a targeting effect on the adipose tissue. In conclusion, CAF in CRB significantly enhanced RSV deposition in adipose tissue and assisted its local-acting effect for managing obesity and cellulite.

Green Synthesis of Cerium Oxide Nanoparticles, Characterization, and Their Neuroprotective Effect on Hydrogen Peroxide-Induced Oxidative Injury in Human Neuroblastoma (SH-SY5Y) Cell Line.

Cerium oxide nanoparticles (CeO2NPs) have a broad scale of applications in the biomedical field due to their excellent physicochemical and catalytic properties. The present study aims to synthesize the CeO2NPs from Centella asiatica (C. asiatica) leaf extract, which has been used in Indian traditional medicine for its neuroprotective properties. The CeO2NPs were characterized by ultraviolet-visible, X-ray diffraction, Fourier transform infrared, Raman spectroscopy, scanning electron microscopy- energy dispersive X-ray spectroscopy, and high-resolution transmission electron microscopy. The antioxidant property was evaluated by 2,2-di (4-tert-octyl phenyl)-1-picrylhydrazyl and OH radical assays. The neuroprotective potential was assessed against the oxidative stress (OS) induced by H2O2 in the human neuroblastoma (SH-SY5Y) cell line. CeO2NPs exhibited significant DPPH and OH radical scavenging activity. Our results revealed that CeO2NPs significantly increased H2O2-induced cell viability, decreased lactate dehydrogenase, protein carbonyls, reactive oxygen species generation, apoptosis, and upregulated antioxidant enzyme activity. Our findings suggest that the CeO2NPs protect the SH-SY5Y cells from OS and apoptosis, which could potentially counter OS-related neurodegenerative disorders.

Preparation and characterization of a curcumin nanoemulsion gel for the effective treatment of mycoses.

Fungal infections of skin including mycoses are one of the most common infections in skin or skins. Mycosis is caused by dermatophytes, non-dermatophyte moulds and yeasts. Various studies show different drugs to treat mycoses, yet there is need to treat it with applied drugs delivery. This study was designed to prepare a bio curcumin (CMN) nanoemulsion (CMN-NEs) for transdermal administration to treat mycoses. The self-nanoemulsification approach was used to prepare a nanoemulsion (NE), utilizing an oil phase consisting of Cremophor EL 100 (Cre EL), glyceryl monooleate (GMO), and polyethylene glycol 5000 (PEG 5000). Particle size (PS), polydispersity index (PDI), zeta potential (ZP), Fourier transform infrared (FTIR) spectrophotometric analysis, and morphological analyses were performed to evaluate the nanoemulsion (NE). The in vitro permeation of CMN was investigated using a modified vertical diffusion cell with an activated dialysis membrane bag. Among all the formulations, a stable, spontaneously produced nanoemulsion was determined with 250 mg of CMN loaded with 10 g of the oil phase. The average droplet size, ZP, and PDI of CMN-NEs were 90.0 ± 2.1 nm, - 7.4 ± 0.4, and 0.171 ± 0.03 mV, respectively. The release kinetics of CMN differed from zero order with a Higuchi release profile as a result of nanoemulsification, which also significantly increased the flux of CMN permeating from the hydrophilic matrix gel. Overall, the prepared nanoemulsion system not only increased the permeability of CMN but also protected it against chemical deterioration. Both CMN-ME (24.0 ± 0.31 mm) and CMN-NE gel (29.6 ± 0.25 mm) had zones of inhibition against Candida albicans that were significantly larger than those of marketed Itrostred gel (21.5 ± 0.34 mm). The prepared CMN-NE improved the bioavailability, better skin penetration, and the CMN-NE gel enhanced the release of CMN from the gel matrix on mycotic patients.

Micelle-Formulated Juglone Effectively Targets Pancreatic Cancer and Remodels the Tumor Microenvironment.

Pancreatic cancer remains a formidable challenge due to limited treatment options and its aggressive nature. In recent years, the naturally occurring anticancer compound juglone has emerged as a potential therapeutic candidate, showing promising results in inhibiting tumor growth and inducing cancer cell apoptosis. However, concerns over its toxicity have hampered juglone's clinical application. To address this issue, we have explored the use of polymeric micelles as a delivery system for juglone in pancreatic cancer treatment. These micelles, formulated using Poloxamer 407 and D-α-Tocopherol polyethylene glycol 1000 succinate, offer an innovative solution to enhance juglone's therapeutic potential while minimizing toxicity. In-vitro studies have demonstrated that micelle-formulated juglone (JM) effectively decreases proliferation and migration and increases apoptosis in pancreatic cancer cell lines. Importantly, in-vivo, JM exhibited no toxicity, allowing for increased dosing frequency compared to free drug administration. In mice, JM significantly reduced tumor growth in subcutaneous xenograft and orthotopic pancreatic cancer models. Beyond its direct antitumor effects, JM treatment also influenced the tumor microenvironment. In immunocompetent mice, JM increased immune cell infiltration and decreased stromal deposition and activation markers, suggesting an immunomodulatory role. To understand JM's mechanism of action, we conducted RNA sequencing and subsequent differential expression analysis on tumors that were treated with JM. The administration of JM treatment reduced the expression levels of the oncogenic protein MYC, thereby emphasizing its potential as a focused, therapeutic intervention. In conclusion, the polymeric micelles-mediated delivery of juglone holds excellent promise in pancreatic cancer therapy. This approach offers improved drug delivery, reduced toxicity, and enhanced therapeutic efficacy.