Encapsulation of Anti-Tuberculosis Drugs within Mesoporous Silica and Intracellular Antibacterial Activities.
Tuberculosis is a major problem in public health. While new effective treatments to combat the disease are currently under development, they tend suffer from poor solubility often resulting in low and/or inconsistent oral bioavailability. Mesoporous materials are here investigated in anin vitrointracellular assay, for the effective delivery of compound PA-824; a poorly soluble bactericidal agent being developed against Tuberculosis (TB). Mesoporous materials enhance the solubility of PA-824; however, this is not translated into a higher antibacterial activity in TB-infected macrophages after 5 days of incubation, where similar values are obtained. The lack of improved activity may be due to insufficient release of the drug from the mesopores in the context of the cellular environment. However, these results show promising data for the use of mesoporous particles in the context of oral delivery with expected improvements in bioavailability.
Department of Materials and Environmental Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm SE-106 91, Sweden. xin@nanologica.com.|Nanologica AB, Drottning Kristinas Väg 61, Stockholm SE-114 28, Sweden. xin@nanologica.com.
Xin
X
Xia
Screening Technologies and Pharmacology Group, Institute Pasteur Korea, Bundang gu, Seongnam-si, Gyeonggi-do 463-742, Korea. kevin.pethe@ip-korea.org.
Kevin
K
Pethe
Screening Technologies and Pharmacology Group, Institute Pasteur Korea, Bundang gu, Seongnam-si, Gyeonggi-do 463-742, Korea. rykim@ip-korea.org.
Ryangyeo
R
Kim
The Diseases of the Developing World Centre, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain. lluis.p.ballell@gsk.com.
Lluis
L
Ballell
The Diseases of the Developing World Centre, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain. david.a.barros@gsk.com.
David
D
Barros
Screening Technologies and Pharmacology Group, Institute Pasteur Korea, Bundang gu, Seongnam-si, Gyeonggi-do 463-742, Korea. jonathancechetto@gmail.com.
Jonathan
J
Cechetto
Screening Technologies and Pharmacology Group, Institute Pasteur Korea, Bundang gu, Seongnam-si, Gyeonggi-do 463-742, Korea. hkhk79@hotmail.com.
HeeKyoung
H
Jeon
Screening Technologies and Pharmacology Group, Institute Pasteur Korea, Bundang gu, Seongnam-si, Gyeonggi-do 463-742, Korea. kideok.kim@ip-korea.org.
Kideok
K
Kim
Department of Materials and Environmental Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm SE-106 91, Sweden. alfonso@mmk.su.se.
Alfonso E
AE
Garcia-Bennett
formulation; intracellular; mesoporous materials; nanomedicine; solubility; tuberculosis