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P1.35 Surface modified solid lipid nanoparticles for the targeted delivery to brain: management of hiv-1 associated dementia
  1. Mani Saurabh Bhargava1,2,
  2. Vishal Bhargava3,
  3. Deepak Shrivastava3
  1. 1ICFAI University, Kanpur, India
  2. 2Himalayan University, Kanpur, India
  3. 3GTB Hospital, Kanpur, India

Abstract

Introduction 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. With Present available treatment system, there is no satisfactory treatment for HAD available.

Methods In this study, nifedipine loaded solid lipid nanoparticles (SLN) were developed for targeting drug into CNS, to block the apoptosis by HIV-1 virus. This would decrease the process of neurodegeneration and increase survival time of neuronal cells. Also, this targeted delivery to brain will minimise the systemic effect of nifedipine, avoiding its delivery peripherally.The uncoated SLN were prepared by Solvent Injection Method and coated with tween 80 and Lyophylized. Shape and surface morphological studies were done by Scanning and Transmission Electron Microscopy (TEM). The in-vitro release profile of entrapped drug was studied using dialysis membrane. Ex-vivo studies consisted of DNA fragmentation followed by in-vivo studies.

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

Conclusion: In-vitro and in-vivo studies results shows more specific delivery of Nifedipine to Brain. DNA Fragmentation and 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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