Risedronate-loaded mPEG-coated hydroxyapatite, thiolated chitosan-based (coated) and non-coated nanoparticles were tested for their potential effects in the treatment of osteoporosis. The prepared nanoparticles were evaluated for their bone-targeting potential by inducing osteoporosis in female Wistar rats via oral administration of Dexona (dexamethasone sodium phosphate). In vivo pharmacokinetic and pharmacodynamic studies were performed on osteoporotic rat models treated with different formulations. The osteoporotic model treated with the prepared nanoparticles indicated a significant effect on bone. The relative bioavailability was enhanced for RIS-HA-TCS-mPEG nanoparticles given orally compared to RIS-HA-TCS, marketed, and API suspension. Biochemical investigations also showed a significant change in biomarker levels, ultimately leading to bone formation/resorption. Micro-CT analysis of bone samples also demonstrated that the RIS-HA-TCS-mPEG-treated group showed the best results compared to other treatment groups. Moreover, the histology of bone treated with RIS-HA-TCS-mPEG showed a marked restoration of the architecture of trabecular bone along with a well-connected bone matrix and narrow inter-trabecular spaces compared to the toxic group. A stability analysis was also carried out according to ICH guidelines (Q1AR2), and it was found that RIS-HA-TCS-mPEG was more stable than RIS-HA-TCS at 25 °C. Thus, the results of present study indicated that mPEG-RIS-HA-TCS has excellent potential for sustained delivery of RIS for the treatment and prevention of osteoporosis, and for minimizing the adverse effects of RIS typically induced via oral administration.

Non-alcoholic fatty liver disease (NAFLD) is a significant consequence of metabolic dysfunction, often associated with changes in the intestinal microbiota. Prebiotics and probiotics have shown promise in NAFLD management. This study evaluated a silymarin-based herbal remedy with piperine and fulvic acid, alongside a probiotic blend of Bifidobacterium adolescentis, Bifidobacterium bifidum, Lactobacillus casei, and Lactobacillus rhamnosus. Using a NAFLD mouse model induced by a high-fat and high-fructose diet, we assessed biochemical parameters, liver function, glucose levels, and conducted histological analysis. Stool samples underwent 16S rRNA metagenomic analysis to explore changes in microbiota composition. Mice on the high-fat diet exhibited elevated lipids, liver enzymes, and glucose, with reduced high-density lipoprotein levels (with p value < 0.001). Treatment, particularly with F3 (silymarin-piperine-fulvic acid herbal remedy and probiotic blend), significantly reduced hepatic fat accumulation and improved gut microbiota composition. This study highlights the potential of silymarin-based therapy combined with probiotics in attenuating NAFLD progression.

Risedronate sodium (RIS) exhibits limited bioavailability and undesirable gastrointestinal effects when administered orally, necessitating the development of an alternative formulation. In this study, mPEG-coated nanoparticles loaded with RIS-HA-TCS were created for osteoporosis treatment. Thiolated chitosan (TCS) was synthesized using chitosan and characterized using DSC and FTIR, with thiol immobilization assessed using Ellman’s reagent. RIS-HA nanoparticles were fabricated and conjugated with synthesized TCS. Fifteen batches of RIS-HA-TCS nanoparticles were designed using the Box–Behnken design process. The nanoparticles were formulated through the ionic gelation procedure, employing tripolyphosphate (TPP) as a crosslinking agent. In silico activity comparison of RIS and RIS-HA-TCS for farnesyl pyrophosphate synthetase enzyme demonstrated a higher binding affinity for RIS. The RIS-HA-TCS nanoparticles exhibited 85.4 ± 2.21% drug entrapment efficiency, a particle size of 252.1 ± 2.44 nm, and a polydispersity index of 0.2 ± 0.01. Further conjugation with mPEG resulted in a particle size of 264.9 ± 1.91 nm, a PDI of 0.120 ± 0.01, and an encapsulation efficiency of 91.1 ± 1.17%. TEM confirmed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. In vitro release studies demonstrated significantly higher release for RIS-HS-TCS-mPEG (95.13 ± 4.64%) compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%), and a marketed formulation (74.69 ± 3.98%). Ex vivo gut permeation studies revealed an apparent permeability of 0.5858 × 10⁻¹ cm/min for RIS-HA-TCS-mPEG, surpassing RIS-HA-TCS (0.4011 × 10⁻⁴ cm/min), RIS suspension (0.2005 × 10⁻⁴ cm/min), and a marketed preparation (0.3401 × 10⁻⁴ cm/min).

Risedronate sodium (RIS) possesses very low bioavailability and several adverse effects in the gastrointestinal tract when administered through an oral route. Thus, this necessitates the need to develop novel formulation. Hence, we had developed RIS-HA-TCS loaded mPEG coated nanoparticles for the treatment of osteoporosis. Chitosan was used to synthesize thiolated chitosan and its characterization was done using DSC and FTIR. Ellman's reagent was used to measure the degree of thiol immobilization. The RIS-HA fabrication was done and was further conjugated with the synthesized TCS. The Box-Behnken design process was used for designing fifteen batches of RIS-HA-TCS nanoparticles, which were formulated by ionic gelation procedure in which tripolyphosphate (TPP) was used as a crosslinking agent. Moreover, RIS and RIS-HA-TCS in-silico activity was compared for farnesyl pyrophosphate synthetase enzyme. The obtained results revealed that the binding affinity of RIS was much more than the conjugated RIS. Successful docking results paved the way for thiolation of chitosan with RIS. The drug entrapment efficiency (%EE), particle size and Polydispersity index (PDI) of RIS-HA-TCS nanoparticles obtained were 85.4 ±2.21%, 252.1 ±2.44 nm and 0.2± 0.01 respectively. The particle size, PDI, and encapsulation efficiency of RIS-HA-TCS were reported to be 264.9 ±1.91 nm, 0.120± 0.01, and 91.1 ±1.17%, respectively, after being further conjugated with mPEG. TEM showed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. The in-vitro release of RIS-HS-TCS-mPEG was found to be significantly higher (95.13±4.64%) as compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%) and marketed formulation (74.69 ± 3.98%). In an ex-vivo gut permeation study, RIS-HA-TCS-mPEG nanoparticles was found to have an apparent permeability of 0.5858×10-1 cm/min which was better than the apparent permeabilities of RIS-HA-TCS formulation (0.4011 ×10-4cm/min), RIS suspension (0.2005 ×10-4 cm/min) and marketed preparation (0.3401 ×10-4 cm/min)..