Central Drug Research Institute

About: Central Drug Research Institute is a facility organization based out in Lucknow, Uttar Pradesh, India. It is known for research contribution in the topics: Catalysis & Leishmania donovani. The organization has 4357 authors who have published 7257 publications receiving 143871 citations. The organization is also known as: Central Drug Research Institute, Lucknow & CDRI.

Development of nanocapsules bearing doxorubicin for macrophage targeting through the phosphatidylserine ligand: a system for intervention in visceral leishmaniasis

Abstract: Objectives: The purpose of this study was to explore the applicability, targeting potential and drug delivery to specialized phagocytes via phosphatidylserine (PS)-specific ligand-anchored nanocapsules (NCs) bearing doxorubicin. Methods: The layer-by-layer method was utilized to prepare NCs having a nanoemulsion core loaded with doxorubicin (NCs-DOX), which was further grafted with PS. PS-coated NCs (PS-NCs-DOX) were compared with NCs-DOX for in vitro targeting ability by studying uptake by macrophages, intracellular localization, in vivo pharmacokinetics and organ distribution studies. The in vivo antileishmanial activity of free doxorubicin, NCsDOX and PS-NCs-DOX was tested against visceral leishmaniasis in Leishmania donovani-infected hamsters. Results: Flow cytometric data revealed 1.75-fold enhanced uptake of PS-NCs-DOX in J774A.1 macrophage cell lines compared with NCs-DOX. In vivo organ distribution studies in Wistar rats demonstrated a significantly higher extent of accumulation of PS-NCs-DOX compared with NCs-DOX in macrophage-rich organs, particularly in liver and spleen. Highly significant antileishmanial activity (P,0.05 compared with NCs) was observed with PS-NCs-DOX, causing 85.23%+4.49% inhibition of splenic parasitic burden. NCs-DOX and free doxorubicin caused only 72.88%+3.87% and 42.85%+2.11% parasite inhibition, respectively, in Leishmania-infected hamsters (P,0.01 for PS-NCs-DOX versus free doxorubicin and NCs-DOX versus free doxorubicin). Conclusions: We conclude that the PS targeting moiety can provide a new insight for efficient drug delivery to specialized macrophages and thus may be developed for effective use in macrophage-specific delivery systems, especially for leishmaniasis.

Intranasal Insulin Administration Ameliorates Streptozotocin (ICV)-Induced Insulin Receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and Memory Impairment in Rats.

Abstract: Alzheimer’s disease (AD) is associated with reduced insulin level and impairment of insulin receptor (IR) signaling in the brain, which correlates to amyloid pathology, neuroinflammation, and synaptic neurotoxicity. Clinical studies show that intranasal insulin improves memory in AD patients without peripheral hypoglycemia. However, neuroprotective molecular mechanism of the beneficial effect of intranasal insulin in AD pathology is unexplored. Therefore, we investigated the role of intranasal insulin on intracerebroventricular (ICV) streptozotocin (STZ)-induced memory impairment in rats as evaluated in the Morris water maze test. STZ (ICV) treated rats had shown memory impairment along with a significant decrease in IR signaling molecules (IR, pIRS-1, pAkt, and pGSK-3α/β expression) and IDE expression in both hippocampus and cerebral cortex. Intranasal insulin delivery prevented these changes. Moreover, intranasal insulin was found to inhibit significantly glial cell activation (GFAP and Iba-1 expression), neuroinflammation (COX-2 expression, NFκB translocation, TNF-α, and IL-10 level) and amyloidogenic protein expression (BACE-1 and Aβ1–42 expression) in STZ (ICV)-injected rats. STZ (ICV)-induced caspase activation and postsynaptic neurotoxicity were also prevented by treatment with intranasal insulin. Our findings reveal that insulin has the neuroprotective effect and clearly signifies the potential use of intranasal insulin delivery for the treatment of AD.