Intracellularly Released Cholesterol from Polymer-Based Delivery Systems Alters Cellular Responses to Pneumolysin and Promotes Cell Survival

Cholesterol is highly abundant within all human body cells and modulates critical cellular functions related to cellular plasticity, metabolism, and survival. The cholesterol-binding toxin pneumolysin represents an essential virulence factor of Streptococcus pneumoniae in establishing pneumonia and other pneumococcal infections. Thus, cholesterol scavenging of pneumolysin is a promising strategy to reduce S. pneumoniae induced lung damage. There may also be a second cholesterol-dependent mechanism whereby pneumococcal infection and the presence of pneumolysin increase hepatic sterol biosynthesis. Here we investigated a library of polymer particles varying in size and composition that allow for the cellular delivery of cholesterol and their effects on cell survival mechanisms following pneumolysin exposure. Intracellular delivery of cholesterol by nanocarriers composed of Eudragit E100–PLGA rescued pneumolysin-induced alterations of lipid homeostasis and enhanced cell survival irrespective of neutralization of pneumolysin.

RESVERATROL-HUMIC ACID LOADED COLLOIDAL POLYMERIC NANOPARTICLES: DESIGN OF EXPERIMENT AND IN VITRO EVALUATION

Objective: The study aims at fabrication and optimization of co-encapsulated resveratrol and humic acid in colloidal polymeric nanocarriers to improves the stability of insoluble antioxidant, resveratrol. Methods: The Eudragit E100 polymeric material was used to fabricate oral co-encapsulation of resveratrol and humic acid in colloidal polymeric nanocarriers, called Res-HA-co-CPNs by an emulsification-diffusion-evaporation method. Taguchi orthogonal array design was employed to check the effect of formulation factors on in vitro physicochemical characteristics. The optimized formulation was further evaluated for stability studies at different conditions. Results: Optimized Res-HA-co-CPNs demonstrated spherical and smooth surface including mean PS 120.56±18.8 nm, PDI 0.122, ZP+38.25mV, and EE 82.37±1.49%. Solid-state characterizations confirmed that optimized Res-HA-co-CPNs showed amorphous characteristics. In vitro release profile of Res-HA-co-CPNs showed an outstanding sustained release behavior up to 48h and remain stable at the refrigerated condition for 6 mo. Conclusion: Res-HA-co-CPNs would be a proficient and promising dosage form for increasing the stability of insoluble antioxidants, resveratrol.

Gd3+ Doped CoFe2O4 Nanoparticles for Targeted Drug Delivery and Magnetic Resonance Imaging

Nanoparticles of CoGdxFe2 − xO4 (x = 0%, 25%, 50%) synthesized via sol–gel auto combustion technique and encapsulated within a polymer (Eudragit E100) shell containing curcumin by single emulsion solvent evaporation technique were formulated in this study. Testing of synthesized nanoparticles was carried out by using different characterization techniques, to investigate composition, crystallinity, size, morphology, surface charge, functional groups and magnetic properties of the samples. The increased hydrophilicity resulted in sustained drug release of 90.6% and 95% for E1(CoGd0.25Fe1.75O4) and E2(CoGd0.50Fe1.5O4), respectively, over a time span of 24 h. The relaxivities of the best-chosen samples were measured by using a 3T magnetic resonance imaging (MRI) machine, and a high r2/r1 ratio of 43.64 and 23.34 for composition E1(CoGd0.25Fe1.75O4) and E2(CoGd0.50Fe1.5O4) suggests their ability to work as a better T2 contrast agent. Thus, these novel synthesized nanostructures cannot only enable MRI diagnosis but also targeted drug delivery.

Characterization of Rheological Property of Mucoadhesive Polymeric Sol-Gel in the Presence of Black Ginger Kaempferia parviflora Extract

The local drug delivery based on mucoadhesion is an effective medical treatment. The mucoadhesive property relies on the formulated gel having optimized rheology. The addition of the drug also showed a major influence towards the sol-gel transition. In this study, compositional effect of Eudragit E100® base polymer, various mucoadhesive polymers, and the black ginger extract on the rheological property of the formulated sol-gel was assessed. It was found that gelling point and gel strength could be tuned mainly based on the concentration of Eudragit E100 limited at 40% w/w due to the viscosity. At Eudragit E100 of 30% w/w, 0.5% w/w herbal extract, and 1%w/w polyvinyl alcohol, the solution reached the gel point at 286 s (tan δ=1) with the gel strength of 1 kPa (G’=G”). For all the formulated sol-gels, the rheological property became better (faster gelling point with the gel strength varying from 100-700 kPa at low strain) a simulated saliva environment.