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. RESULTS: Optimized NE had a droplet size of 38.70 ± 3.11nm, PDI of 0.14 ± 0.0024, refractive index of 1.43 ± 0.01, transmittance of 98.12 ± 0.07 %, zeta potential of - 27.4 ± 0.14 mV, and viscosity of 19.67 ± 0.25 Pa s. Behavioral studies showed that 6-OHDA induced PD in rats were successfully reversed when administered with NRG NE intranasally along with the levodopa. While the levels of GSH and SOD were significantly higher, levels of MDA were significantly lower in the group treated with NRG NE via intranasal route along with levodopa. CONCLUSION: Encouraging results from current study provide evidence for possible efficacy of a novel noninvasive intranasal delivery system of NRG for management of PD related symptoms.

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 (85.7 ± 7.3 nm), drug entrapment efficiency (87.4 ± 3.29%), and in vitro drug release characteristics (92.89 ± 5.47%). The optimized ISD-NLC formulation also demonstrated well-dispersed uniform-shaped particles (polydispersity index 0.207 ± 0.029), high gastrointestinal fluid stability (zeta potential -10.17 ± 0.59 mV), and higher in vitro gut permeation (21.69 ± 2.38 µg/cm2 of ISD-NLC as compared to 11.23 ± 1.74 µg/cm2 in ISD suspension). Furthermore, lipolysis studies were performed for the purpose of in vivo fate, and significantly higher drug content of ISD from ISD-NLC in aqueous phase was found (72.34 ± 4.62%) as compared to drug suspension (3.01 ± 0.91%). Relative bioavailability of ISD-NLC and ISD suspension was increased by 4.2-fold and 1.78-fold in the absence and presence of cycloheximide which is a lymphatic uptake inhibitor revealing lymphatic uptake of ISD-NLC in bioavailability improvement. Hence, systematic adaptation of quality by design integrated approach improved gut permeation and potential solubilizaton fate (dynamic lipolysis) of ISD-NLC, which further improved the lymphatic uptake and biodistribution of drug thereby promisingits in vivo prospect and clinical efficacy.

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. The present review provides an insight into the challenges associated with the conventional antihypertensive formulations and need for oral nanoparticulate systems in order to overcome problems associated with conventional formulations. Hypertension has circadian pattern of blood pressure, therefore chronotherapeutics can play a decisive role for the treatment, and however, nanoparticulate system can play major role in hypertension management. Future prospective for particulate nanocarriers in drug delivery for hypertension includes chronotherapeutics and emerging technique like gene therapy which is also covered in the review.

Brain delivery of buspirone hydrochloride chitosan nanoparticles for the treatment of general anxiety disorder.

The present work discusses the preparation, characterization and in vivo evaluation of thiolated chitosan nanoparticles (TCS-NPs) of buspirone hydrochloride (BUH) for brain delivery through intranasal route. TCS NPs were prepared by ionic gelation method and characterized for various parameters. The NPs formed were having particle size of 226.7±2.52nm with PDI 0.483±0.031. Drug entrapment efficiency (EE) and loading capacity (LC) were found to be 81.13±2.8 and 49.67±5.5%. The cumulative percentage drug permeation through nasal mucosa was 76.21%. Bioadhesion study carried out on porcine mucin and showed a bioadhesion efficiency of 90.218±0.134%. Nose-to-brain delivery of placebo NPs was investigated by confocal laser scanning microscopy (CLSM) technique using rhodamine-123 as a marker. The brain concentration achieved after intranasal administration of TCS-NPs was 797.46±35.76ng/ml with tmax 120min which was significantly higher than achieved after intravenous administration on BUH solution 384.15±13.42ng/ml and tmax of 120min and intranasal administration of BUH solution 417.77±19.24ng/ml and tmax 60min.

Nanostructured lipid (NLCs) carriers as a bioavailability enhancement tool for oral administration.

CONTEXT: Nanostructured lipid carrier (NLCs) is the second generation solid lipid nanoparticles (NPs) made up of physiological, biocompatible, biodegradable, non-sensitizing and non-irritating lipids. OBJECTIVE: The main objective of this review is to explore the role of NLCs system for delivering drugs by oral route and thus increasing the oral bioavailability. METHODS: The present review article highlights the definition and types of NLCs and their importance as colloidal carriers including the production techniques and their formulation. This review article also deals with the fate of lipids used in the NLCs formulation and the NLCs toxicity. CONCLUSION: On the basis of the literature survey done, it was concluded that the NLCs enhances the oral bioavailability of the drug and may decrease the side effects and toxicity of the lipids used in other polymeric NPs as NLCs uses physiological and biodegradable lipids.