Title
Thermosensitive sol-gel system containing vancomycin-loaded thiomeric nanoparticles for enhanced permeation across nasal membrane
Authors
SAMIA TABASSUM, HAFIZ SHOAIB SARWAR, MUHAMMAD SAFRAZ, OMER SALMAN QURESHI, AAMIR JALIL, MUHAMMAD ASAD SAEED, MUHAMMAD AMER, MUHAMMAD FARHAN SOHAIL, ZULCAIF, SYFYAN JUNAID USMANI and FARID MENAA

Received July 4, 2024
Published Volume 58 Issue 9-10 September-December
Keywords thiomer, biomolecules, in-situ gelling, nano-carriers, chitosan, enhanced permeation

Abstract
During oral delivery, vancomycin (VAN) is prone to enzymatic degradation and therefore, an intra-nasal highly mucoadhesive system, having enhanced nasal residence time, is considered in this study as an alternative way for vancomycin delivery. It was aimed to develop highly mucoadhesive in-situ gelling nanoparticles (NPs) by combining two mucoadhesive technologies: i.e. thiolation and thermosetters for nasal delivery of vancomycin. For this purpose, thiolated chitosan was synthesized, and the degree of thiolation was determined via Ellman’s test. In the next step, vancomycin-loaded nanoparticles based on chitosan (CS-NP) and thiolated chitosan (TCS-NP-PL) were prepared and coated with 20% (w/w) solution of pluronic to form thiolated thermosensitive in-situ gelling systems. Nanoparticles were assessed for particle size (PS), zeta potential (ZP), morphology, gelling time, viscosity, swelling index, and gelling temperature. Likewise, CS-NP and TCS-NP-PL were evaluated for mucoadhesion, ex-vivo drug permeation across the nasal membrane, and in-vitro drug release. TCS-NP-PL showed gelation at 32 ± 0.5 °C in 45 ± 2 seconds. TCS-NP-PL showed a maximum mucoadhesion of up to 210 min. In vitro drug release studies revealed that CS-NP, TCS-NPs, and TCS-NPs-PL showed 55%, 54.6%, and 52.1% drug release, respectively, during 24 h. TCS-NP-PL exhibited 6.40-fold enhanced permeation across nasal mucosa, as compared to free drugs. TCS-NP-PL significantly increased nasal residence time and permeability of VAN, supporting the concept of combined use of thiolation and thermo in-situ gelling system for prolonged contact with nasal mucosa, providing increased transport across nasal membrane.