Department of Pharmacy

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Author: search.filters.author.Sakhuja, RajeevHas files: No

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    Synthesis of modified bile acids via palladium-catalyzed C(sp3)–H (hetero)arylation
    (RSC, 2023-07) Chitkara, Deepak; Sakhuja, Rajeev
    A Pd(II)-catalyzed strategy for the diastereo- and regioselective (hetero)arylation of unactivated C(sp3)–H bonds in bile acids is accomplished with aryl and heteroaryl iodides under solvent-free conditions using the 8-aminoquinoline auxiliary as a directing group. This methodology demonstrated excellent functional group tolerance with respect to aryl/heteroaryl iodides on O-protected N-(quinolin-8-yl)cholyl/deoxycholyl amides to afford β-C(sp3)–H (hetero)arylated products in good-to-excellent yields. Moreover, the 8-aminoquinoline (AQ) auxiliary can easily be removed to obtain modified bile acids.
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    Folate-Targeted Cholesterol-Grafted Lipo-Polymeric Nanoparticles for Chemotherapeutic Agent Delivery
    (Springer, 2020-10) Mittal, Anupama; Chitkara, Deepak; Sakhuja, Rajeev
    Docetaxel (DTX), an FDA approved chemotherapeutic agent, is used as a first-line treatment for triple-negative breast cancer (TNBC). Its poor aqueous solubility, rapid metabolism, short half-life, and effective targeting to the cancer cells limits its optimal therapeutic use. Herein, we report folate targeted amphiphilic lipopolymer grafted with cholesterol conjugated carbonate and DL-lactide prepared by microwave assisted ring opening polymerization, for the efficient actively targeted delivery of DTX. The DTX-loaded folate-targeted lipopolymeric nanoparticles (F-DTX-LPNs) prepared by the emulsion solvent evaporation method exhibited a smaller size of ∼115.17 nm with a PDI of 0.205 and encapsulation efficiency of >80%. Further, these lipopolymeric nanoparticles (F-DTX-LPNs) showed a good on-bench stability and sustained DTX release for 7 days. Cell-based assays in MDA-MB-231 cells revealed a significant enhancement in the intracellular uptake of folate-targeted lipopolymeric nanoparticles compared to non-targeted nanoparticles. Further, methyl beta-cyclodextrin (Mβ-CD) completely inhibited the uptake of these nanoparticles in the cells, indicating a lipid raft-mediated uptake mechanism. The developed F-DTX-LPNs showed improved cytotoxicity, apoptosis, and significant fold-change in expression levels of Bcl-2, BAX and Ki-67 as compared to non-targeted DTX-LPNs and free DTX. Further, F-DTX-LPNs showed an improved in vivo pharmacokinetic profile in Sprague Dawley rats as compared to the free DTX. The bio-imaging of ex vivo tissues demonstrated that the DiR loaded folate targeted LPNs exhibited intense signals after 24 h because of slow release of DiR dye from the nanoparticles.