Abstract:
:Existing therapies yield low drug encapsulation or accumulation in the lungs, hence the site-specific drug delivery remains the challenge for tuberculosis. Lately, dry powder inhalers (DPIs) are showing promising drug deposition in the deeper lung tissues. Biocompatible polymers with the ability to naturally recognize and bind to the surface receptors of alveolar macrophages, the reservoir of the causative organism, were selected. DPIs comprised of chitosan (CS)/thiolated chitosan (TC) in conjugation with Hyaluronic acid (HA) were synthesized loaded with isoniazid (INH) by using the Design of Experiment (DoE) approach. Nanosuspensions were prepared by ionic gelation method using cross-linker, sodium-tripolyphosphate (TPP) and were optimized by using Box-Behnken 3-level screening design and later freeze-dried to obtain nanopowders. Physico-chemical compatibility of nanoplex systems was investigated using in-vitro characterization techniques. In-vitro release and permeation studies were correlated in terms of the pattern of drug content dissolved over time. In addition, the cytotoxicity studies on A549 cells demonstrated the safety profile of the nanoplexes. Moreover, in-silico studies and aerodynamic profiles verify the suitability of DPIs for further in-vivo tuberculosis therapeutics. DoE analyses affirmed the lack of linearity in the model for the certain response of studied parameters in a holistic way, which was not possible else ways.
journal_name
Int J Biol Macromoljournal_title
International journal of biological macromoleculesauthors
Mukhtar M,Pallagi E,Csóka I,Benke E,Farkas Á,Zeeshan M,Burián K,Kókai D,Ambrus Rdoi
10.1016/j.ijbiomac.2020.10.192subject
Has Abstractpub_date
2020-12-15 00:00:00pages
3007-3019issue
Pt Beissn
0141-8130issn
1879-0003pii
S0141-8130(20)34845-5journal_volume
165pub_type
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