Nanostructured lipid carriers of isradipine for effective management of hypertension and isoproterenol induced myocardial infarction.

The objective of the present paper is to formulate nanostructured lipid carriers (NLCs) of a calcium channel blocker, isradipine, to enhance its oral bioavailability and prolong its antihypertensive effect apart from evaluating efficacy of the formulation in isoproterenol induced myocardial infarction in rats. Formulation was optimized using quality by design (QbD)-based approach. Three factors i.

Design of efficacious somatic cell genome editing strategies for recessive and polygenic diseases.

Compound heterozygous recessive or polygenic diseases could be addressed through gene correction of multiple alleles. However, targeting of multiple alleles using genome editors could lead to mixed genotypes and adverse events that amplify during tissue morphogenesis. Here we demonstrate that Cas9-ribonucleoprotein-based genome editors can correct two distinct mutant alleles within a single human cell precisely.

Vitamin E Loaded Naringenin Nanoemulsion via Intranasal Delivery for the Management of Oxidative Stress in a 6-OHDA Parkinson's Disease Model.

Purpose: The present study is an attempt to develop a vitamin E loaded naringenin (NRG) Nanoemulsion (NE) for direct nose-to-brain delivery for better management of Parkinson's disease (PD).

Methods: The optimized NE was evaluated for efficacy in PD using multiple behavioral studies (including narrow beam test, muscular coordination test, grip strength test, forced swimming test, and akinesia test) in a rat model. Optimized formulation was evaluated for droplet size, polydispersity index (PDI), refractive index, transmittance, zeta potential, and viscosity.

Optimization of Nanostructured Lipid Carriers of Lurasidone Hydrochloride Using Box-Behnken Design for Brain Targeting: In Vitro and In Vivo Studies.

Intranasal nanostructured lipid carrier (NLC) of lurasidone hydrochloride (LRD) for brain delivery was prepared by the solvent evaporation method. The effects of independent variables, X1-lipid concentration, X-2 surfactant, and X-3 sonication times on dependent variables, Y1-particle size, Y-2 polydispersity index, and Y-3% entrapment efficiency were determined using Box-Behnken design. Optimized LRD-NLC was selected from the Box-Behnken design and evaluated for their morphological, physiological, nasal diffusion, and in vivo distribution in the brain after intranasal administration.

Adaptation of Quality by Design-Based Development of Isradipine Nanostructured-Lipid Carrier and Its Evaluation for In Vitro Gut Permeation and In Vivo Solubilization Fate.

The present study demonstrated the systematic adaptation of quality by design-integrated approach for the development of novel nanostructured lipid carrier (NLC) of an anti-hypertensive drug isradipine (ISD) to address the inherent challenges such as low solubility and low oral bioavailability. Plackett-Burman design was used for preliminary screening of significant process and formulation variables (p <0.05), which were further processed using Box-Behnken design for the attainment of optimization goal that is, mean particle size (85.

Nanocarriers as treatment modalities for hypertension.

Hypertension, a worldwide epidemic at present, is not a disease in itself rather it is an important risk factor for serious cardiovascular disorders including myocardial infarction, stroke, heart failure, and peripheral artery disease. Though numerous drugs acting via different mechanism of action are available in the market as conventional formulations for the treatment of hypertension but they face substantial challenges regarding their bioavailability, dosing and associated adverse effects which greatly limit their therapeutic efficacies. Various studies have demonstrated that nanocarriers can significantly increase the drug bioavailability thereby reducing the frequency of dosing in addition to minimizing toxicity associated with high dose of the drug.

Insulin gene therapy for type 1 diabetes mellitus.

Type 1 diabetes mellitus is an autoimmune disease resulting from the destruction of pancreatic β cells. Current treatments for patients with type 1 diabetes mellitus include daily insulin injections or whole pancreas transplant, each of which are associated with profound drawbacks. Insulin gene therapy, which has shown great efficacy in correcting hyperglycemia in animal models, holds great promise as an alternative strategy to treat type 1 diabetes mellitus in humans.

Optimization of nanostructured lipid carriers of lamotrigine for brain delivery: in vitro characterization and in vivo efficacy in epilepsy.

Objective: The aim of the present work was to investigate the efficacy of nanostructured lipid carriers (NLCs) to enhance the brain targeting of lamotrigine (LMT) following intranasal (IN) administration.

Methods: Formulation was optimized using four-factor three levels Box- Behnken design to establish the functional relationships between variables on responses, that is, particle size, entrapment efficiency (EE) and percentage cumulative drug release of LMT-loaded NLCs. NLCs were evaluated for particle size, surface morphology, %EE and in vitro release and ex vivo permeation.

Loin pain hematuria syndrome.

Loin pain hematuria syndrome is a rare disease with a prevalence of ∼0.012%. The most prominent clinical features include periods of severe intermittent or persistent unilateral or bilateral loin pain accompanied by either microscopic or gross hematuria.

Correction of Diabetic Hyperglycemia and Amelioration of Metabolic Anomalies by Minicircle DNA Mediated Glucose-Dependent Hepatic Insulin Production.

Type 1 diabetes mellitus (T1DM) is caused by immune destruction of insulin-producing pancreatic β-cells. Commonly used insulin injection therapy does not provide a dynamic blood glucose control to prevent long-term systemic T1DM-associated damages. Donor shortage and the limited long-term success of islet transplants have stimulated the development of novel therapies for T1DM.

Selenium-binding protein-1 in smooth muscle cells is downregulated in a rhesus monkey model of chronic allograft nephropathy.

Treating patients with kidney failure by organ transplantation has been extraordinarily successful. Although, current immunosuppressants have improved short-term allograft survival, most transplants are eventually lost due to chronic allograft nephropathy (CAN). The molecular mechanisms underlying CAN are poorly understood.

Hepatic insulin gene therapy in insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease resulting in destruction of the pancreatic beta-cells in the islets of Langerhans. Commonly employed treatment of IDDM requires periodic insulin therapy, which is not ideal because of its inability to prevent chronic complications such as nephropathy, neuropathy and retinopathy. Although pancreas or islet transplantation are effective treatments that can reverse metabolic abnormalities and prevent or minimize many of the chronic complications of IDDM, their usefulness is limited as a result of shortage of donor pancreas organs.

Glucose-regulated insulin production in hepatocytes.

Background: A gene-therapy-based treatment of type 1 diabetes mellitus requires the development of a surrogate beta cell that can synthesize and secrete functionally active insulin in response to physiologically relevant changes in ambient glucose levels. Failure to duplicate the storage-granule-based mechanism of insulin secretion of beta cells, however, has made it difficult to develop a surrogate beta cell. The authors' strategy for achieving glucose-dependent insulin secretion relies on glucose-responsive transcription of insulin mRNA and the constitutive secretory pathway of liver cells.