Global incidence of superficial fungal infections caused by dermatophytes is high and affects around 40 million people. It is the fourth most common cause of infection. Clotrimazole, a broad spectrum imidazole antifungal agent is widely used to treat fungal infections. Conventional topical formulations of clotrimazole are intended to treat infections by effective penetration of drugs into the stratum corneum. However, drawbacks such as poor dermal bioavailability, poor penetration, and variable drug levels limit the efficiency. The present study aims to load clotrimazole into ufosomes and evaluate its topical bioavailability. Clotrimazole loaded ufosomes were prepared using cholesterol and sodium oleate by thin film hydration technique and evaluated for size, polydispersity index, and entrapment efficiency to obtain optimized formulation. Optimized formulation was characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). Skin diffusion studies and tape-stripping were performed using human skin to determine the amount of clotrimazole accumulated in different layers of the skin. Results showed that the optimized formulation had vesicle size <250 nm with ~84% entrapment efficiency. XRD and DSC confirmed the entrapment of clotrimazole into ufosomes. No permeation was observed through the skin up to 24 h following the permeation studies. Tape-stripping revealed that ufosomes led to accumulation of more clotrimazole in the skin compared to marketed formulation (Perrigo). Overall, results revealed the capability of ufosomes in improving the skin bioavailability of clotrimazole.
Age related macular degeneration (AMD) is one of the leading causes of visual loss and is responsible for approximately 9% of global blindness. It is a progressive eye disorder seen in elderly people (>65 years) mainly affecting the macula. Lutein, a carotenoid, is an antioxidant, and has shown neuroprotective properties in the retina. However, lutein has poor bioavailability owing to poor aqueous solubility. Drug delivery to the posterior segment of the eye is challenging due to the blood–retina barrier. Retinal pigment epithelium (RPE) expresses the sodium-dependent multivitamin transporter (SMVT) transport system which selectively uptakes biotin by active transport. In this study, we aimed to enhance lutein uptake into retinal cells using PLGA–PEG–biotin nanoparticles. Lutein loaded polymeric nanoparticles were prepared using O/W solvent-evaporation method. Particle size and zeta potential (ZP) were determined using Malvern Zetasizer. Other characterizations included differential scanning calorimetry, FTIR, and in-vitro release studies. In-vitro uptake and cytotoxicity studies were conducted in ARPE-19 cells using flow cytometry and confocal microscopy. Lutein was successfully encapsulated into PLGA and PLGA–PEG–biotin nanoparticles (<250 nm) with uniform size distribution and high ZP. The entrapment efficiency of lutein was ≈56% and ≈75% for lutein-loaded PLGA and PLGA–PEG–biotin nanoparticles, respectively. FTIR and DSC confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies in ARPE-19 cells confirmed a higher uptake of lutein with PLGA–PEG–biotin nanoparticles compared to PLGA nanoparticles and lutein alone. In vitro cytotoxicity results confirmed that the nanoparticles were safe, effective, and non-toxic. Findings from this study suggest that lutein-loaded PLGA–PEG–biotin nanoparticles can be potentially used for treatment of AMD for higher lutein uptake.
1 February 2020 in European Journal of Pharmaceutical Sciences
A global outbreak of the SARS-CoV-2 virus has infected millions of people over a short period of time. The communicability and increased mortality from the SARS-CoV-2 infection mandated the WHO to declare COVID-19 a worldwide pandemic. The virus outbreak has spread when there are no approved vaccines, treatments, or prophylactic therapies available. Researchers from all over the world have prioritised development of vaccines and antivirals. Several vaccine projects have seen successes in preclinical, phase I, and phase II clinical trials using recombinant DNA, mRNA, live attenuated virus, S-protein subunits, virus like particles, and viral vectors. Initial findings from antivirals such as remdesivir, favipiravir, danoprevir or lopinavir with ritonavir are presented. Immunomodulatory molecules such as sarilumab, tocilizumab, janus kinase inhibitors, and hyperimmune convalescent plasma have mixed outcomes from initial clinical findings; however, pending randomised controlled trials will assist national health institutions to make treatment recommendations for COVID-19. Where compassionate use of remdesivir has shown some benefits, therapies such as hydroxychloroquine have proven harmful due to their toxicities. This review discusses pharmacological interventions at play and evidence-based successes and limitations of non-pharmacological therapies such as social distancing, personal protective equipment, and ventilator support associated with the prevention and treatment of COVID-19.
8 April 2021 in Journal of Materials Science: Materials in Medicine
This study evaluates the suitability of 3D printed biodegradable mats to load and deliver the topical antibiotic, neomycin, for up to 3 weeks in vitro. A 3D printer equipped with a hot melt extruder was used to print bandage-like wound coverings with porous sizes appropriate for cellular attachment and viability. The semicrystalline polyester, poly-l-lactic acid (PLLA) was used as the base polymer, coated (post-printing) with polyethylene glycols (PEGs) of MWs 400 Da, 6 kDa, or 20 kDa to enable manipulation of physicochemical and biological properties to suit intended applications. The mats were further loaded with a topical antibiotic (neomycin sulfate), and cumulative drug-release monitored for 3 weeks in vitro. Microscopic imaging as well as Scanning Electron Microscopy (SEM) studies showed pore dimensions of 100 × 400 µm. These pore dimensions were achieved without compromising mechanical strength; because of the “tough” individual fibers constituting the mat (Young’s Moduli of 50 ± 20 MPa and Elastic Elongation of 10 ± 5%). The in vitro dissolution study showed first-order release kinetics for neomycin during the first 20 h, followed by diffusion-controlled (Fickian) release for the remaining duration of the study. The release of neomycin suggested that the ability to load neomycin on to PLLA mats increases threefold, as the MW of the applied PEG coating is lowered from 20 kDa to 400 Da. Overall, this study demonstrates a successful approach to using a 3D printer to prepare porous degradable mats for antibiotic delivery with potential applications to dermal regeneration and tissue engineering.
To prepare and characterise lutein-loaded polylactide-co-glycolide–polyethylene glycol–folate (PLGA-PEG-FOLATE) nanoparticles and evaluate enhanced uptake in SK-N-BE(2) cells. Nanoparticles were pr...