RT Journal Article
T1 Design and synthesis of multifunctional polymeric micelles for targeted delivery in Helicobacter pylori infection
A1 Qaiser, Aimen
A1 Kiani, Maria Hassan
A1 Parveen, Rashida
A1 Sarfraz, Muhammad K.
A1 Shahnaz, Gul
A1 Rahdar, Abbas
A1 Taboada Antelo, Pablo
K1 Nanomicelles
K1 Targeted delivery
K1 Mucoadhesion
K1 Mucopenetration
K1 H. pylori infection
AB This study aimed to design a hyaluronic acid-based targeted, mucoadhesive and mucopenetrating drug delivery system encapsulating clarithromycin that would improve the drug residence time at H. pylori infection site. Clarithromycin-loaded thiolated hyaluronic acid-co-oleic acid (CLR-thHA-co-OA), clarithromycin-loaded ureido-conjugated thiolated hyaluronic acid-co-oleic acid (CLR-Ur-thHA-co-OA), and clarithromycin-loaded papain-modified ureido-conjugated thiolated hyaluronic acid-co- oleic acid (CLR-PAP-Ur-thHA-co-OA) nanomicelles were prepared by an ultra-sonication method. FTIR data confirmed the successful grafting of the different ligands to polymer backbone. XRD analysis revealed the amorphous nature of the polymer conjugate and drug inside nanomicelles. The critical micelle concentration of PAP-Ur-thHA-co-OA nanomicelles was found to be 15.85 µg/ml. Also, the sizes of nanomicelles were in the range of 210–258 nm. TEM analysis of CLR-PAP-Ur-thHA-co-OA nanomicelles confirmed their small size and spherical shape. Zeta potential and entrapment efficiency of CLR-PAP-Ur-thHA-co-OA nanomicelles were –24 mV and 80 ± 7.2% respectively. A sustained drug release pattern was observed for all types of prepared nanomicelles, whereas CLR-PAP-Ur-thHA-co-OA ones also displayed improved stability at acidic pH. Due to the presence of thiol groups in the polymer backbone, thiolated nanomicelles displayed important mucoadhesive properties. In this regard, FDA loaded PAP-Ur-thHA-co-OA nanomicelles showed the deepest penetration distance into the mucus by cleavage of mucoglycoproteins when compared to papain-unmodified nanomicelles. Fluorescent images of gastric tissues revealed the greater gastric retention time of nanomicelles compared to the free drug. As consequence, an enhanced in vitro efficacy against H. pylori was observed by nanomicelles. The in vivo clearance study showed an improved eradication of H. pylori by CLR-PAP-Ur-thHA-co-OA nanomicelles in comparison to other nanoformulations. Thus, the newly synthesized CLR-PAP-Ur-thHA-co-OA nanomicelles have the potential to be used as an efficient nanocarrier for H. pylori infection treatment due to their enhanced mucopenetration and mucoadhesion properties, as well as their improved stability and extended drug release
PB Elsevier
YR 2022
FD 2022
LK http://hdl.handle.net/10347/29158
UL http://hdl.handle.net/10347/29158
LA eng
NO Journal of Molecular Liquids 363 (2022) 119802
NO P.T also thanks Agencia Estatal de Investigación (AEI) by project PID2019-109517RB-I00. ERDF funds are also acknowledged
DS Minerva
RD 26 abr 2026