Brain targeted intra nasal acyclovir lipid nanoparticles; in-vitro characterization and in-vivo biodistribution studies.

Acyclovir (ACY) is an antiviral class of drugs used to treat herpes simplex virus infections such as herpes simplex encephalitis (HSE). ACY is widely distributed; Systemic exposure of ACY leads to serious adverse effects. Because of its high pH, intravenous ACY may cause phlebitis and local inflammation if extravasation occurs. This study aims to enhance acyclovir delivery to the brain via the intranasal route by formulating ACY nano lipid carriers (ACY-NLCs) to circumvent the side-effects, as mentioned earlier. ACY-NLCs were prepared by emulsification, followed by ultrasonication. A Box-Behnken statistical design with three factors, three levels and 17 runs was selected for the optimization study using Design- Expert Software. Nanoparticles were characterized for particle size, entrapment efficiency and in-vitro drug release. ACY- NLC showed biphasic release pattern i.e. an initial faster release followed by sustained release. Biodistribution study by imaging, Nanoparticles were slowly cleared and biodistributed to the other organs was observed in 2nd and 3rd hr post-administration. From the toxicity studies, NLC formulation is safe and non-toxic for the nasal administration. Rhodamine loaeded NLCs were quickly adsorbed by the olfactory tract and distributed mainly to the lungs through respiratory tract and were also detected in the trachea and olfactory bulb. Biodistribution study of dye loaded NLCs reach brain compared to the Rhodamine-solution.

Prospective of managing impaired brain insulin signalling in late onset Alzheimers disease with excisting diabetic drugs.

Late onset Alzheimer's disease (AD) is the most common cause of dementia among elderly. The exact cause of the disease is until now unknown and there is no complete cure for the disease. Growing evidence suggest that AD is a metabolic disorder associated with impairment in brain insulin signalling. These findings enriched the scope for the repurposing of diabetic drugs in AD management. Even though many of these drugs are moving in a positive direction in the ongoing clinical studies, the extent of the success has seen to influence by several properties of these drugs since they were originally designed to manage the peripheral insulin resistance. In depth understandings of these properties is hence highly significant to optimise the use of diabetic drugs in the clinical management of AD; which is the primary aim of the present review article.

Repositioning of Itraconazole for the Management of Ocular Neovascularization Through Surface-Modified Nanostructured Lipid Carriers.

Retinopathy is one of the most common complications of diabetes. Approximately 80% of patients with diabetes history for over 10 years suffer from some degree of diabetic retinopathy (DR). Currently available treatments include use of antivascular endothelial growth factor-165 (VEGF165) agents or steroids. However, they are very expensive, involve an invasive procedure that is painful, and show ocular and systemic complications. Currently, the focus for treatment of such disorders has shifted from new drug discovery to repositioning of available drugs because of the cost and time consumption involved in the former. Working on this strategy, itraconazole (ITR) was selected for treatment of DR due to its potent unutilized antiangiogenic activity for the management of DR. An attempt was made to develop a topical, noninvasive nanostructured lipid carrier (NLC) owing to the potential to carry entrapped drug across the membranes. ITR-NLCs were prepared using high-pressure homogenization by applying Box-Behnken design for optimization. Surface of NLCs was modified by chitosan (CS) coating. ITR-NLCs were examined for antiangiogenic potential and their VEGF165 targeting efficiency. Drug-loaded NLC showed desired particle size, zeta potential, and polydispersity index. In VEGF-induced DR rats, ITR and CS-ITR-NLCs were found to exhibit an antineovascularization effect by targeting VEGF165. The developed CS-ITR-NLC proved to be an effective topical therapy for management of DR, offering the advantages of cost-effectiveness, higher patient compliance, and better tolerance.

Nose to brain transport pathways an overview: potential of nanostructured lipid carriers in nose to brain targeting.

Many of the therapeutics used for the treatment of brain disorders are not effective and not delivered to the brain due to the complex structure and its barriers. In recent years, many advanced approaches have emerged for the brain drug delivery. Intranasal drug delivery is one of non-invasive approach has gained interest because of direct transport of drugs circumventing the brain barriers through olfactory and trigeminal nerve pathways. Eventhough through these pathways the therapeutics have direct access to the brain, the main limitations of this approach are only limited drug absorption, and nasal permeability. To overcome the issues related to the brain targeting via nasal drug delivery encourage the development of novel drug delivery by combining with nanotechnology. This article will discuss pathways of drug transport form nose to brain, toxicity of nanoparticles role and need of nanostructured lipid carriers (NLCs) and recent advance in combination of NLCs with intranasal drug delivery for targeting the brain.

Malaria treatment using novel nano-based drug delivery systems.

We reside in an era of technological innovation and advancement despite which infectious diseases like malaria remain to be one of the greatest threats to the humans. Mortality rate caused by malaria disease is a huge concern in the twenty-first century. Multiple drug resistance and nonspecific drug targeting of the most widely used drugs are the main reasons/drawbacks behind the failure in malarial therapy. Dose-related toxicity because of high doses is also a major concern. Therefore, to overcome these problems nano-based drug delivery systems are being developed to facilitate site-specific or target-based drug delivery and hence minimizing the development of resistance progress and dose-dependent toxicity issues. In this review, we discuss about the shortcomings in treating malaria and how nano-based drug delivery systems can help in curtailing the infectious disease malaria.

Current treatment strategies and nanocarrier based approaches for the treatment and management of diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of blindness in all working age groups which contribute to patient's quality of life. Considering the anatomy and physiology of barriers in the eye, the treatment and management of pathologic ocular neovascularization in the posterior segment of the eye in DR is a challenging task. The current and emerging treatment strategies are discussed in this review for better understanding and treatment of the DR. Challenges in conventional therapy and recent developments in nanocarrier based approaches (polymeric, lipid nanoparticles, liposomes and dendrimers) and their advantages in targeting ocular tissues were also discussed in this review.