A Comprehensive Review on Nanoparticles as Drug Delivery System and Their Role for Management of Hypertension.

The current global epidemic of hypertension is not a disease in and of itself but rather a significant risk factor for serious cardiovascular conditions such as peripheral artery disease, heart failure, myocardial infarction, and stroke. Although many medications that work through various mechanisms of action are available on the market in conventional formulations to treat hypertension, these medications face significant difficulties with their bioavailability, dosing, and associated side effects, which significantly reduces the effectiveness of their therapeutic interventions. Numerous studies have shown that nanocarriers and nanoformulations can minimize the toxicity associated with high doses of the drug while greatly increasing the drug's bioavailability and reducing the frequency of dosing.

This review sheds light on the difficulties posed by traditional antihypertensive formulations and highlights the necessity of oral nanoparticulate systems to solve these issues. Because hypertension has a circadian blood pressure pattern, chronotherapeutics can be very important in treating the condition. On the other hand, nanoparticulate systems can be very important in managing hypertension.

Mannose-Functionalized Isoniazid-Loaded Nanostructured Lipid Carriers for Pulmonary Delivery: In Vitro Prospects and In Vivo Therapeutic Efficacy Assessment.

Resistance to isoniazid (INH) is common and increases the possibility of acquiring multidrug-resistant tuberculosis. For this study, isoniazid-loaded nanostructured lipid carriers (INH-NLCs) were developed and effectively functionalized with mannose (Man) to enhance the residence time of the drug within the lungs via specific delivery and increase the therapeutic efficacy of the formulation. The mannose-functionalized isoniazid-loaded nanostructured lipid carrier (Man-INH-NLC) formulation was evaluated with respect to various formulation parameters, namely, encapsulation efficiency (EE), drug loading (DL), average particle size (PS), zeta potential (ZP), polydispersity index (PDI), in vitro drug release (DR), and release kinetics. The in vitro inhalation behavior of the developed formulation after nebulization was investigated using an Andersen cascade impactor via the estimation of the mass median aerosolized diameter (MMAD) and geometric aerodynamic diameter (GAD) and subsequently found to be suitable for effective lung delivery. An in vivo pharmacokinetic study was carried out in a guinea pig animal model, and it was demonstrated that Man-INH-NLC has a longer residence time in the lungs with improved pharmacokinetics when compared with unfunctionalized INH-NLC, indicating the enhanced therapeutic efficacy of the Man-INH-NLC formulation. Histopathological analysis led us to determine that the extent of tissue damage was more severe in the case of the pure drug solution of isoniazid compared to the Man-INH-NLC formulation after nebulization. Thus, the nebulization of Man-INH-NLC was found to be safe, forming a sound basis for enhancing the therapeutic efficacy of the drug for improved management in the treatment of pulmonary tuberculosis.

Effect of Different Molecular Weights of Chitosan on Formulation and Evaluation of Allopurinol-Loaded Nanoparticles for Kidney Targeting and in Management of Hyperuricemic Nephrolithiasis.

Present research study was conducted to formulate kidney-targeted allopurinol (AO)-loaded chitosan nanoparticles (ANPs) for management of hyperuricemic related nephrolithiasis. Different molecular weights of chitosan were used for fabricating ANP formulation by adopting modified ionotropic gelation method. The prepared batches were than evaluated for particle size analysis, entrapment efficiency, transmission electron microscopy, X-ray diffraction, Differential Scanning Calorimetry, in vitro release and in vivo animal study. The in vivo study depicted that post 2 h of administration of different formulations and pure drug; ANPs prepared from low molecular weight chitosan showed maximum concentration of AO in kidney signifying successful kidney targeting of drug (25.92 fold) whereas no or very less amount of AO was seen in other animal groups. Effectiveness (p < 0.01) of formulation in management of hyperuricemia-associated nephrolithiasis was also evaluated via estimation of urine pH and serum and urine uric acid levels of mice. Further histological study was also performed on kidney samples which again affirmed these results. Present investigation demonstrated that ANPs prepared from low MW chitosan depicted maximum kidney-targeting ability that might be due to its specific uptake by the kidneys as well as its higher solubility than other two polymers, which results in enhanced release rate from the formulation and also offers an efficient strategy for the management of hyperuricemic nephrolithiasis.

Formulation, Characterization, and Pharmacokinetic Evaluation of Novel Glipizide-phospholipid Nano-complexes with Improved Solubility and Bio-availability.

BACKGROUND: The proposed study was aimed to formulate and evaluate the glipizidephospholipid nano-complex. Since glipizide is a poorly soluble drug, its complexation with phospholipids is an ideal approach to improving solubility. METHODS: To improve the oral potency of glipizide, its phospholipid complex was prepared by employing the solvent evaporation method. The formulations were characterized using DSC, FTIR, PXRD, SEM, TEM, and hot stage microscopy (HSM). Solubility tests of the glipizidephospholipid nano-complex revealed a significant increase in aqueous solubility compared to glipizide's physical combination. The oral bioavailability of the glipizide-phospholipid nanocomplex was measured by using HPLC in Wistar rats' plasma. FTIR and PXRD results revealed no significant interaction between the drug and the phospholipid in the formulation. SEM and TEM studies confirmed the morphology of the formulation assuring the conversion of crystalline form into an amorphous structure. RESULTS: The glipizide-phospholipid nano-complex had a greater peak plasma concentration (5.2 vs. 3.8 g/mL), a larger AUC (26.31 vs. 19.55 µgh/L), and a longer T1/2 (2.1 vs. 4.1 h) than free glipizide, indicating that it improved drug dissolution rate. CONCLUSION: The outcomes suggested that a phospholipid complexation is a potential approach to increasing water-insoluble drugs' oral bioavailability.

Development and in-vitro evaluation of transdermal matrix films of metoprolol tartrate.

The transdermal matrix films of metoprolol tartrate (MT) were prepared by casting on mercury substrate employing different ratios of polymers, ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP), using dibutyl phthalate (DBT) as a plasticizer. Four formulations were prepared. Formulations MF-1, MF-2, MF-3 and MF-4 were composed of EC and PVP in the following ratios: 4.5:0.5, 4:1, 3:2 and 2:3 respectively. The formulations were subjected to various physical characterization studies namely, thickness, weight variation, drug content, moisture uptake, in vitro drug release and in vitro skin permeation. The in vitro permeation studies were carried out across excised porcine ear skin using Franz diffusion cell. Cumulative amounts of the drug released in 24 hours from the four formulations were 69.58%, 96.13%, 98.85% and 99.60%, respectively. Corresponding values for the cumulated amounts of drug permeated across the porcine skin for the above matrix films were 124.38, 153.22, 156.46 and 163.25 mug/cm(2) respectively. By fitting the data into zero order, first order and Higuchi model, it was concluded that drug release from matrix films followed Higuchi model (r(2)=0.9147-0.9823), and the mechanism of release was diffusion mediated. Based on the physical evaluation, in vitro drug release & permeation characteristics, it was concluded that for potential therapeutic use, monolithic drug matrix films MF-3, composed of EC: PVP (3:2), may be suitable for the development of a transdermal drug delivery system of MT.