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In this study, we report the development and evaluation of soy lecithin-chitosan hybrid nanoparticles to improve the oral bioavailability of raloxifene hydrochloride. The nanoparticles were formed by interaction of negatively charged soy lecithin with positively charged chitosan. The ratio of soy lecithin to chitosan was critical for the charge, and hence the size of the nanoparticles. The optimal soy lecithin to chitosan ratio was 201 to obtain nanoparticles with particle size of 208 ± 3 nm, a ζ-potential of 36 ± 2 mV and an entrapment efficiency of 73 ± 3%. The nanoparticles were also characterized by differential scanning calorimetry and FT-IR spectrophotometer. In-vitro drug release was assessed using dialysis bag method in pH 7.4 buffer. The drug loaded nanoparticles did not cause significant reduction in the cell viability at low doses. Pharmacokinetic studies in female Wistar rats showed significant improvement (~4.2 folds) in the oral bioavailability of the drug when loaded into nanoparticles. Further, the modified everted gut sac study showed that these nanoparticles are taken up by active endocytic processes in the intestine. The ex-vivo mucoadhesion studies proved that the nanoparticles get bound to the mucus layer of the intestine, which in turn correlates with reduced excretion of the drug in faeces. In conclusion, the proposed nanoparticles appear promising for effective oral delivery of poorly bioavailable drugs like raloxifene hydrochloride.AmyloLipid nanovesicles (ALNs) are new lipid-modified starch complex nanoparticles developed and presented as nanocarriers of curcumin for targeting the CNS via the intranasal route. Curcumin has been indicated as a promising active agent with a variety of pharmacological activities, including a potential ability to treat brain tumors, traumatic brain injury, and CNS disorders, such as Alzheimer's disease, as it may inhibit amyloid-β-protein (Aβ) aggregation and Aβ-induced inflammation. Although curcumin has a tremendous potential as a therapeutic agent for CNS disorders, its low bioavailability and its rapid total body clearance reduce any chance for therapeutic levels to reach the brain. https://www.selleckchem.com/ By using an optimized (2% crosslinked starch) curcumin-loaded ALNs, which was fabricated from a microemulsion as a precursor, an average of 141.5 ± 55.9 ng/g brain levels and 11.9 ± 12.0 ng/ml plasma concentrations were detected, one hour following intranasal administration of 160 μg/kg dose of curcumin. In comparison, 1 h after IV administration of the same dose, no CUR was detected in the brain and the mean plasma level was approximately one half of the level monitored after intranasal ALNs, i.e., 7.25 ± 0.20 ng/ml. It has been clearly demonstrated, therefore, that a well-designed ALN formulation proved itself as a promising carrier for intranasal delivery and brain targeting of curcumin.Multimodal therapeutic approach has been gaining lot of attention for effective therapy of cancer. In the present work, a novel and unique pH responsive nanoplatform have been developed for multimodal therapy of glioblastoma using protein, biopolymer and MOFs. Lactoferrin (Lf) has been used as protein matrix for loading titanocene which was then enclosed in ZIF-8 framework along with 5-FU (ZIF-8@Lf-TC). The ZIF-8 was further coated with Lenalidomide-HA conjugate linked via hydrazone linkage (LND-HA@ZIF-8@Lf-TC). The developed nanocomposite was extensively characterized using spectroscopic, x-ray and electron microscopic techniques. The nanocomposites were evaluated for pH responsive drug release, stability, bio-interaction, and haemocompatibility which confirmed pH responsive nature of nanocomposite, stability and absence of any significant interaction with biomolecules. In obtained results for in vitro cell line studies performed in U87MG and RAW264.7 cells demonstrated enhanced cell cytotoxicity against cancer cells which was further supported by results of cellular ROS generation and surface ROS generation by nanocomposites. The Zinc and Lf mediated disruption of intracellular IL-6 and TNFα levels was observed with synthesized nanocomposites. They demonstrated pH responsive release of 5-FU and LND along with sustained release of both drugs in simulated medium. The LND-HA@ZIF-8@Lf-TC demonstrated superior cell growth supressing ability compared to ZIF-8@Lf-TC and ZIF-8. The nanocomposites were stable in biomimicking environment as well as did not show any significant interaction with RBC, plasma or CSF. The overall results suggest that LND-HA@ZIF-8@Lf-TC can be explored as promising platform for dual drug delivery mediated multimodal therapy of cancer.Cell-based injectable therapy utilizing stem cells is a promising approach for the treatment of stress urinary incontinence (SUI). Applying a magnetically controlled cell delivery approach has enormous potential to enhance cell retention capability within the specified site. To assess the therapeutic efficacy of cellular magnetic targeting, we applied an external magnetic force to target an adipose-derived stem cell based therapy in a rat model of SUI. The results revealed that magnetic attraction of transplanted cells under the magnetic field was generated by cell uptake of superparamagnetic iron oxide nanoparticles in vitro. More importantly, magnetic targeting improved the retention rate of transplanted cells and facilitated the restoration of sphincter structure and function in a rat SUI model according to the results of histological examination and urodynamic testing. Therefore, magnetically guided targeting strategy might be a potential therapy method for treatment of SUI. Multiple modifications of reverse total shoulder arthroplasty (RTSA) since the first Grammont design have developed to improve range of motion (ROM) and avoid notching. The effect of these changes in shoulder kinematics and the best compromise for ROM is still under debate. This computer simulation study evaluates the influence of humeral design, humeral neck-shaft angle (NSA), glenoid lateralization, and glenoid eccentricity on ROM of RTSA. We created a 3-dimensional computer model from computed tomographyscans of 13 patients with primary osteoarthritis simulating implantation of a standardized reverse shoulder arthroplasty. We analyzed the effect of 4 different variables on impingement-free ROM humeral design (inlay vs. semi-inlay vs. onlay), humeral NSA (135°vs. 145°vs. 155°), glenoid lateralization, and glenoid eccentricity on ROM. The use of different humeral stem designs did not have a significant effect on total global ROM. Reducing NSA demonstrated a significant increase in adduction, and external and internal rotation in adduction, whereas a decrease in abduction and external rotation in abduction.
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