QbD-Assisted Development and Optimization of Doxycycline Hyclate- and Hydroxyapatite-Loaded Nanoparticles for Periodontal Delivery.

The current research aims to develop a carrier system for the delivery of a matrix metalloproteinase (MMP) inhibitor along with a bioceramic agent to the periodontal pocket. It is proposed that the present system, if given along with a systemic antibiotic, would be a fruitful approach for periodontitis amelioration. To fulfill the aforementioned objective, a doxycycline hyclate- and hydroxyapatite-adsorbed composite was prepared by a physical adsorption method and successfully loaded inside sodium alginate-chitosan nanoparticles and optimized based on particle size and drug content. Optimized formulation was then subjected to different evaluation parameters like encapsulation efficiency, hydroxyapatite content, ζ potential, surface morphology, in vitro drug release, cell line studies, and stability studies. For the optimized formulation, particle size, polydispersity index (PDI), entrapment efficiency, ζ potential, and drug content were found to be 336.50 nm, 0.23, 41.77%, -13.85 mV, and 14.00%, respectively. The surface morphology of the placebo and adsorbed composite-loaded nanoparticles as observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the spherical shape and rough surface of the particles. In gingival crevicular fluid (GCF) 7.6, a sustained drug release profile was obtained up to 36 h. In vitro % viability studies performed on murine fibroblast cells (NIH3T3) and human periodontal ligament (hPDL) cell lines confirmed the proliferative nature of the formulation. Also, when subjected to stability studies for 4 weeks, particle size, PDI, and drug content did not vary considerably, thereby ensuring the stable nature of nanoparticles. Henceforth, sodium alginate-chitosan nanoparticles appeared to be a good carrier system for doxycycline hyclate and hydroxyapatite for periodontal therapy. If given along with a system antibiotic, the system will serve as a fruitful tool for infection-mediated periodontal regeneration and healing.

Fat fighting liraglutide based nano-formulation to reverse obesity: Design, development and animal trials.

Obesity is a metabolic disease, which is one of the major causes of morbidity and mortality, where therapeutic options are limited. Treatment of obesity is necessary as it is associated with fatal complications like diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, osteoarthritis, and many more. Liraglutide (Lir), a synthetic analogue of Glucagon-like Peptide-1 (GLP-1), is the FDA approved anti-obesity drug, however, its major limitation is its clinical application which needs frequent parenteral injections. To address the issue of regular injection, we have synthesized a fat fighting oral nano-formulation of liraglutide with a sustained release feature, which was evaluated against high fat diet (HFD) induced obesity in mice. Experimental obesity was induced in mice by feeding HFD for 26 weeks. Lir nanoparticles (NP) were fabricated with chitosan via ion-gelation technique and were coated with Eudragit@S100 to protect the drug in harsh gastric conditions. Physiochemical characterization of Eu-Lir-Cs-NP demonstrated a small particle size of 253.1 ± 1.21 nm with âˆ¼ 9.74 % loading and âˆ¼ 72.11 % encapsulation efficiency of the drug. In-vitro studies showed successful cellular uptake of NP in Caco-2 cells and were stable in various enteric fluid pH conditions. Eudragit@S100 coated chitosan NP were able to protect the drug from harsh gastric pH conditions with more than âˆ¼ 74% of recovery. Treatment of two weeks of liraglutide Eu-Lir-Cs-NP (0.1, 0.2 and 0.4 mg/kg, orally; twice daily) moderately reduces obesity in mice as evidenced by a reduction in the body weight, blood glucose, serum total cholesterol, serum triglyceride, serum resistin and serum insulin level of mice. In addition, significant reduction of liver weight, abdominal white adipose tissue, and hepatic oxidative stress were noted. Our results suggest that chitosan-based NP of liraglutide can be an effective and convenient formulation for the management of obesity.

Solid Lipid Nanoformulation of Berberine Attenuates Doxorubicin Triggered in vitro Inflammation in H9c2 Rat Cardiomyocytes.

AIM: The aim of this study was to evaluate the efficacy of solid lipid nanoparticles of berberine against doxorubicin-induced cardiotoxicity. BACKGROUND: Berberine (Ber) is cardioprotective, but its oral bioavailability is low, and its effect on chemotherapy-induced cardiotoxicity has not been studied. OBJECTIVE: Solid lipid nanoparticles (SLNs) of berberine chloride were prepared, characterized and evaluated in vitro against doxorubicin-induced cardiomyocyte injury. METHODS: Berberine-loaded SLNs (Ber-SLNs) were synthesized using the water-in-oil microemulsion technique with tripalmitin, Tween 80 and poloxamer 407. Ber-SLNs were evaluated for preventive effect against toxicity of doxorubicin in H9c2 cells. The culture was pre-treated (24 h) with Ber (10 µM) and Ber-SLNs (1 and 10 µM), and 1 µM of doxorubicin (Dox) was added for 3 h. The cell viability assay (MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) and LDH (Lactate dehydrogenase)), levels of Creatine kinase-MB (CK-MB), Nitrite, MDA (Malondialdehyde), ROS (Reactive oxygen species) generation, and apoptotic DNA (Deoxyribonucleic acid) content were assessed. RESULTS: Ber-SLNs had a mean particle size of 13.12±1.188 nm, the zeta potential of -1.05 ± 0.08 mV, poly-dispersity index (PDI) of 0.317 ± 0.05 and entrapment efficiency of 50 ± 4.8%. Cell viability was 81 ± 0.17% for Ber-SLNs (10 µM) and 73.22 ± 0.83% for Ber (10 µM) treated cells in the MTT assay. Percentage cytotoxicity calculated from LDH release was 58.91 ± 0.54% after Dox, 40.3 ± 1.3% with Ber (10 µM) and 40.7 ± 1.3% with Ber-SLNs (1 µM) (p<0.001). Inflammation and oxidative stress markers were lower with Ber and Ber-SLNs. Attenuation of ROS generation and apoptosis of cardiomyocytes were noted on fluorescence microscopy. CONCLUSION: Ber SLNs effectively prevented doxorubicin-induced inflammation and oxidative stress in rat cardiomyocytes. The results demonstrate that microemulsion is a simple and costeffective technique to prepare Ber-SLNs, and may be considered as a drug delivery vehicle for berberine.