In silico screening of drug candidates for thermoresponsive liposome formulations

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F21%3A43922871" target="_blank" >RIV/60461373:22340/21:43922871 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/21:73610657 RIV/61989592:15640/21:73610657

Result on the web

<a href="https://doi.org/10.1039/D0ME00160K" target="_blank" >https://doi.org/10.1039/D0ME00160K</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d0me00160k" target="_blank" >10.1039/d0me00160k</a>

Result language

angličtina

Original language name

In silico screening of drug candidates for thermoresponsive liposome formulations

Original language description

Liposomal formulations can be advantageous in many scenarios such as targeted delivery to reduce the systemic toxicity of highly potent active pharmaceutical ingredients (APIs), to increase drug bioavailability by prolonging systemic circulation, to protect labile APIs from degradation in the gastrointestinal tract, or to improve skin permeation in dermal delivery. However, not all APIs are suitable for encapsulation in liposomes. Some of the issues are too high permeability of the API across the lipid bilayer, which may lead to premature leakage, too low permeability, which may hinder the drug release process, or too strong membrane affinity, which may reduce the overall efficacy of drug release from liposomes. Since the most reliable way to test API encapsulation and release from liposomes so far has been experimental, an in silico model capable of predicting API transport across the lipid bilayer might accelerate formulation development. In this work, we demonstrate a new in silico approach to compute the temperature-dependent permeability of a set of compounds across the bilayer of virtual liposomes constructed by molecular dynamics simulation. To validate this approach, we have conducted a series of experiments confirming the model predictions using a homologous series of fluorescent dyes. Based on the performance of individual molecules, we have defined a set of selection criteria for identifying compatible APIs for stable encapsulation and thermally controlled release from liposomes. To further demonstrate the in silico-based methodology, we have screened the DrugBank database, identified potent drugs suitable for liposome encapsulation and successfully carried out the loading and thermal release of one of them-the antimicrobial compound cycloserine. This journal is © The Royal Society of Chemistry.

Czech name

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Czech description

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Type

J_SC - Article in a specialist periodical, which is included in the SCOPUS database

CEP classification

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OECD FORD branch

20401 - Chemical engineering (plants, products)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Systems Design &amp; Engineering (MSDE)

ISSN

2058-9689

e-ISSN

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Volume of the periodical

6

Issue of the periodical within the volume

5

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

368-380

UT code for WoS article

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EID of the result in the Scopus database

2-s2.0-85105744668