Objective: In this study, nifedipine loaded solid lipid nanoparticles (SLN) were developed for targeting drug into the central nervous system, the site of action of drug to block the apoptosis by HIV-1 virus. This would decrease the process of neurodegeneration and increase the survival time of neuronal cells. Also, this targeted delivery to brain will minimize the systemic effect of nifedipine, avoiding its delivery peripherally.

Background: HIV-Associated Dementia (HAD) is a significant neurological complication which occurs years after the acute viral sero-conversion reaction responsible for progressive Immuno-suppression and high viral loads. Many patients infected with HIV-1 suffer cognitive impairment ranging from mild to severe HAD which may result from neuronal death in the basal ganglia, cerebral cortex, and hippocampus. With Present available treatment system, there is no satisfactory treatment for HAD available, despite of advancement in the therapeutics.

Methods: The uncoated SLN were prepared by Solvent Injection Method & then coated with tween 80 and Lyophylized. Shape & surface morphological studies were done by Scanning Electron Microscopy (SEM) & Transmission Electron Microscopy (TEM). The in-vitro release profile of entrapped drug was studied using dialysis membrane. The Ex-vivo studies consisted of DNA fragmentation followed by in-vivo studies on albino rats.

Results: The SEM & TEM images show the smooth & spherical surface of SLN. The in-vitro release profile of drug shows more than 90% of drug release in 48hrs. DNA fragmentation was determined in presence and in absence of gp120 mimicking agent which shows no DNA fragmentation thus the developed carrier system works properly in releasing the drug and blocking apoptosis in the cortical cells. The fluorescence microscopy shows the qualitative uptake and localization pattern of the coated SLNs in brain.

Conclusions: In-vitro & in-vivo studies results shows more specific delivery of the Nifedipine to the Brain. The DNA Fragmentation & Cell Viability studies shows dementia blocking activity on brain cells. Brain specific delivery of Nifedipine could reduce the dose and potential systemic side effects, thus providing site specific delivery to brain. Thus, CNS delivery of these Nifedipine loaded SLNs via Intra Venous delivery will also open new opportunities for other Anti-Retroviral drug delivery to brain.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/surface-modified-solid-lipid-nanoparticles-for-the-targeted-delivery-to-brain-management-of-hiv-1-associated-dementia/