Cationic Bovine Serum Albumin (CBA) conjugated Poly Lactic-co-Glycolic Acid (PLGA) nanoparticles for extended delivery of methotrexate into brain tumor

Current treatment strategies for the treatment of brain tumor have been hindered primarily by the presence of highly lipophilic insurmountable blood-brain barrier (BBB). The purpose of current research was to investigate the efficiency of engineered biocompatible polymeric nanoparticles (NPs) as drug delivery vehicle to bypass the BBB and enhance biopharmaceutical attributes of anti-metabolite methotrexate (MTX) encapsulated NPs. The NPs were prepared by solvent diffusion method using cationic bovine serum albumin (CBA), and characterized for physicochemical parameters such as particle size, polydispersity index, and zeta-potential; while the surface modification was confirmed by FTIR, and NMR spectroscopy. Developed NPs exhibited zestful relocation of FITC tagged NPs across BBB in albino rats. Further, hemolytic studies confirmed them to be non-toxic and biocompatible as compared to free MTX. In vitro cytotoxicity assay of our engineered NPs on HNGC1 tumor cells proved superior uptake in tumor cells; and elicited potent cytotoxic effect as compared to plain NPs and free MTX solution. The outcomes of the study evidently indicate the prospective of CBA conjugated poly (D,L-lactide-co-glycolide) (PLGA) NPs loaded with MTX in brain cancer bomber with amplified capability to circumvent BBB.

Mental Health and Morbidity of Caregivers and Co-Residents of individuals with Dementia: A Quasi-Experimental Design

Objectives: To determine if providing informal care to a co-resident with dementia symptoms places an additional risk on the likelihood of poor mental health or mortality compared to co-resident non-caregivers.
Design: A quasi-experimental design of caregiving and non-caregiving co-residents of individuals with dementia symptoms, providing a natural comparator for the additive effects of caregiving on top of living with an individual with dementia symptoms. 
Methods: Census records, providing information on household structure, intensity of caregiving, presence of dementia symptoms and self-reported mental health, were linked to mortality records over the following 33 months. Multi-level regression models were constructed to determine the risk of poor mental health and death in co-resident caregivers of individuals with dementia symptoms compared to co-resident non-caregivers, adjusting for the clustering of individuals within households.
Results: The cohort consisted of 10,982 co-residents (55.1% caregivers), with 12.1% of non-caregivers reporting poor mental health compared to 8.4% of intense caregivers (>20 hours of care per week). During follow-up the cohort experienced 560 deaths (245 to caregivers). Overall, caregiving co-residents were at no greater risk of poor mental health but had lower mortality risk than non-caregiving co-residents (ORadj=0.93, 95% CI 0.79, 1.10 and ORadj=0.67, 95% CI 0.56, 0.81, respectively); this lower mortality risk was also seen amongst the most intensive caregivers (ORadj=0.65, 95% CI 0.53, 0.79).
Conclusion: Caregiving poses no additional risk to mental health over and above the risk associated with merely living with someone with dementia, and is associated with a lower mortality risk compared to non-caregiving co-residents.