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.

Formulation and optimization of intranasal nanolipid carriers of pioglitazone for the repurposing in Alzheimer's disease using Box-Behnken design.

Growing evidence suggest that Alzheimer's disease (AD), the most common cause of dementia among the elderly is a metabolic disorder associated with impaired brain insulin signaling. Hence, the diabetic drug can be a therapeutic option for the management AD. The researches in this area are ongoing and Pioglitazone (PIO) is one of the most investigated diabetic drug in AD. Eventhough PIO treatment was found to improve AD significantly in the preclinical models, the poor blood-brain barrier (BBB) permeability and serious peripheral side effects limited its success in the clinical trials. The objective of the present study was to formulate and optimize intranasal (IN) nano lipid carriers (NLC) of PIO for its targeted delivery to the brain. A Box-Behnken design was employed to optimize the effect of three independent variables on two dependent variables. The optimized formulation had a particle size (PS) of 211.4 ± 3.54 nm and zeta potential of (ZP) of 14.9 ± 1.09 mv. The polydispersibility index (PDI) and entrapment efficiency (EE) was found to be 0.257 ± 0.108 and 70.18 ± 4.5% respectively. Storage stability studies performed has confirmed the stability of NLCs at 4 °C and 25 °C. The in-vitro drug release study has exhibited a sustained release of drug from the NLC. The formulation was observed to improve the nasal permeability of PIO ex-vivo significantly. Toxicity studies were performed to confirm the safety of formulation for the in-vivo administration. In-vivo biodistribution study in rats has shown a direct transport of drug from the nose to brain from the IN-NLC.

Scope of new formulation approaches in the repurposing of pioglitazone for the management of Alzheimer's disease.

WHAT IS KNOWN AND OBJECTIVE: Alzheimer's disease (AD) is the most common cause of dementia among the elderly. The exact cause of the disease is not clearly known, and no existing therapies are able to prevent disease progression. Identification of the possible "impaired brain insulin signalling in AD" enriched the scope for "the repurposing of diabetic drugs in AD management." Among the different classes of diabetic drugs, pioglitazone (PIO), a PPARγ agonist classed as an insulin sensitizer, is of the highest interest for AD management. The drug is reported to have direct action on multiple targets involved in AD, independent of insulin signalling. Even though PIO has appeared to be a potent molecule in preclinical trials, limited success was observed in the clinical stage. The tentative reasons for the limited therapeutic success in the clinical stage are not clear. The main focus of the review is to discuss various factors that might limit the therapeutic success of PIO in clinical trials and possible approaches to overcome those limitations. METHOD: The research articles, review articles, and patents containing information regarding the clinical and preclinical trials of PIO in AD have been reviewed thoroughly using the keywords related to diabetic drugs in AD, PIO for AD management and mechanism of PIO in AD. Literature search was conducted on PubMed, SCOPUS and EMBASE. RESULTS AND DISCUSSION: Previous studies have indicated that the blood-brain barrier (BBB) is the biggest challenge to delivering PIO to the brain. Therefore, to attain a therapeutic concentration in the brain, a higher dose is needed, which is also supported by preclinical investigations in AD; however, in clinical studies, scientists have used the usual diabetic doses. This dose is inadequate to attain a therapeutic concentration in the brain and appears to be the primary reason for the limited success of PIO in clinical trials. The stage of drug intervention and the nature of the study population are also influential factors for the therapeutic response. WHAT IS NEW AND CONCLUSION: The insufficient concentration of the drug reaching the brain appears to be the crucial factor that limits the therapeutic success of PIO in AD management. Since the administration of higher doses cannot be recommended due to safety issues, the current situation demands the use of novel tools to ensure a therapeutic concentration reaches 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.