ArticleBeilstein journal of organic chemistry2017
Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann-Pick type C disease-like HepG2 cells.
Article in Beilstein journal of organic chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 18 citations in OpenAlex.
- Synthesis and Preliminary Evaluation of an ASGPr-Targeted PolycationicPharmaceutics · 2024Article
- Review
- In vivo Efficacy and Safety Evaluation of Lactosyl-β-cyclodextrin as a Therapeutic Agent for Hepatomegaly in Niemann-Pick Type C Disease.Nanomaterials (Basel, Switzerland) · 2019Article
- Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies.Beilstein journal of organic chemistry · 2018Article
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Authors and funding
9 authors at 1 institution in 1 country.
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Abstract
Niemann-Pick type C (NPC) disease, characterized by intracellular accumulation of unesterified cholesterol and other lipids owing to defects in two proteins NPC1 and NPC2, causes neurodegeneration and other fatal neurovisceral symptoms. Currently, treatment of NPC involves the use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). HP-β-CD is effective in the treatment of hepatosplenomegaly in NPC disease, albeit at a very high dose. One of the methods to reduce the required dose of HP-β-CD for treatment of NPC is to actively targeting hepatocytes with β-cyclodextrin (β-CD). The aim of the present study was to synthesize a novel multi-lactose-appended β-CD (multi-Lac-β-CD) and to evaluate its cholesterol-lowering effect in U18666A-treated HepG2 (NPC-like HepG2) cells. Further, the study aimed at delivering β-CD to hepatocytes via cholesterol-accumulated HepG2 cells, and indicated that the newly synthesized multi-Lac-β-CD had an average degree of substitution of lactose (DSL) of 5.6. This newly synthesized multi-Lac-β-CD was found to significantly decrease the concentration of intracellular cholesterol with negligible cytotoxicity as compared to HP-β-CD. An increased internalization of TRITC-multi-Lac-β-CD (DSL 5.6) as compared to TRITC-HP-β-CD was observed in NPC-like HepG2 cells. Further, the dissociation constant of peanut lectin with multi-Lac-β-CD (DSL5.6) was found to be extremely low (2.5 × 10
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