Polymeric micelles loaded in situ gel with prednisolone acetate for ocular inflammation: development and evaluation.

Aim: Our study developed a prednisolone acetate polymeric micelles (PM) system for ocular inflammation related to allergic uveitis. Methods: For PM development, a thin-film hydration procedure was used. Irritation, in vitro, ex vivo transcorneal permeation, micelle size, entrapment efficiency and histology within the eye were all calculated for PM. Results: The optimized in situ gel (A4) showed superior ex vivo transcorneal permeation with zero-order kinetics. Conclusion: The developed formulation could be a promising candidate for treating anterior uveitis via topical application to the anterior segment of the eye.

A Review on Polymeric Nanostructured Micelles for the Ocular Inflammation-Main Emphasis on Uveitis.

BACKGROUND: Various types of nano-formulations are being developed and tested for the delivery of the ocular drug. They also have anatomical and physiological limitations, such as tear turnover, nasal lachrymal waste, reflex squinting, and visual static and dynamic hindrances, which pose challenges and delay ocular drug permeation. As a result of these limitations, less than 5% of the dose can reach the ocular tissues. OBJECTIVE: The basic purpose of designing these formulations is that they provide prolonged retention for a longer period and can also increase the course time. METHODS: To address the aforementioned issues, many forms of polymeric micelles were developed. Direct dissolving, dialysis, oil-in-water emulsion, solvent evaporation, co-solvent evaporation, and freeze-drying are some of the methods used to make polymeric nano micelles. RESULTS: Their stability is also very good and also possesses reversible drug loading capacity. When the drug is given through the topical route, then it has very low ocular bioavailability. CONCLUSION: The definition and preparation process of polymeric micelles and anti-inflammatory drugs used in uveitis and the relation between uveitis and micelles are illustrated in detail.

QbD-based rivastigmine tartrate-loaded solid lipid nanoparticles for enhanced intranasal delivery to the brain for Alzheimer's therapeutics.

Alzheimer's disease (AD) is a neurodegenerative disease that affects a wide range of populations and is the primary cause of death in various countries. The treatment of AD is still restricted to oral conventional medicines that act only superficially. Fabrication of intranasal solid lipid nanoparticulate system for the uptake of therapeutic agents will act as a convincing approach with limited off-site toxicity and increased pharmacological activity. The objective of this study was to formulate, optimize, and evaluate the efficiency of rivastigmine tartrate (RT)-loaded intranasal solid lipid nanoparticles (SLNs) employing the solvent-evaporation diffusion method. To optimize the formulation parameters, the central composite design (CCD) was used. Lipid concentration (X1) and surfactant concentration (X2) were considered to be independent variables, while particle size (Y1), percentage entrapment efficiency (Y2), and percentage drug release (Y3) were considered as responses. The solid lipid was glyceryl monostearate, while the surfactant was polysorbate 80. The optimized formulation has a particle size of 110.2 nm, % entrapment efficiency of 82.56%, and % drug release of 94.86%. The incompatibility of drug excipients was established by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Nasal histopathology tests on sheep mucosa revealed that the developed SLNs were safe to utilize for intranasal delivery with no toxicity. Ex vivo permeation investigations revealed that the flux and diffusion coefficients for RT solid lipid nanoparticles and RT solution were 3.378 g/cm2 /h and 0.310-3 cm2 /h, respectively. Stability studies demonstrated that the developed SLNs were stable when stored under various storage conditions. The viability and vitality of adopting a lipid particle delivery system for improved bioavailability via the intranasal route were also established in the in vivo pharmacokinetic investigations. According to the histopathological and pharmacokinetic investigations, the developed formulations were safe, non-lethal, efficient, and robust. These results suggest the potentiality provided by rivastigmine tartrate-loaded solid lipid nanoparticles for nasal delivery.

Southern hemisphere forced millennial scale Indian summer monsoon variability during the late Pleistocene.

Peninsular India hosts the initial rain-down of the Indian Summer Monsoon (ISM) after which winds travel further east inwards into Asia. Stalagmite oxygen isotope composition from this region, such as those from Belum Cave, preserve the vital signals of the past ISM variability. These archives experience a single wet season with a single dominant moisture source annually. Here we present high-resolution δ18O, δ13C and trace element (Mg/Ca, Sr/Ca, Ba/Ca, Mn/Ca) time series from a Belum Cave stalagmite spanning glacial MIS-6 (from ~ 183 to ~ 175 kyr) and interglacial substages MIS-5c-5a (~ 104 kyr to ~ 82 kyr). With most paleomonsoon reconstructions reporting coherent evolution of northern hemisphere summer insolation and ISM variability on orbital timescale, we focus on understanding the mechanisms behind millennial scale variability. Finding that the two are decoupled over millennial timescales, we address the role of the Southern Hemisphere processes in modulating monsoon strength as a part of the Hadley circulation. We identify several strong and weak episodes of ISM intensity during 104-82 kyr. Some of the weak episodes correspond to warming in the southern hemisphere associated with weak cross-equatorial winds. We show that during the MIS-5 substages, ISM strength gradually declined with millennial scale variability linked to Southern Hemisphere temperature changes which in turn modulate the strength of the Mascarene High.