Lipopolysaccharide Polyelectrolyte Complex for Oral Delivery of an Anti-tubercular Drug
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Anti-tuberculosis drug delivery has remained a challenge due to inconsistent bioavailability and inadequate sustained-release properties leading to treatment failure. To resolve these drawbacks, a lipopolysaccharide polyelectrolyte complex (PEC) encapsulated with rifampicin (RIF) (as the model drug) was fabricated, using the solvent injection technique (SIT), with soy lecithin (SLCT), and low-molecular-weight chitosan (LWCT). The average particle size and surface charge of RIF-loaded PEC particulates was 151.6 nm and + 33.0 nm, respectively, with noted decreased particle size and surface charge following increase in SLCT-LWCT mass ratio. Encapsulation efficiency (%EE) and drug-loading capacity (%LC) was 64.25% and 5.84%, respectively. Increase in SLCT-LWCT mass ratio significantly increased %EE with a marginal reduction in %LC. In vitro release studies showed a sustained-release profile for the PEC particulate tablet over 24 h (11.4% cumulative release) where the dominant release mechanism involved non-Fickian anomalous transport shifting towards super case II release as SLCT ratios increased (6.4% cumulative release). PEC-tablets prepared without SIT presented with rapid Fickian-diffusion-based drug release with up to 90% RIF release within 4 h. Ex vivo permeability studies revealed that lipopolysaccharide PEComplexation significantly increased the permeability of RIF by ~ 2-fold within the 8-h study period. These results suggest successful encapsulation of RIF within a PEC structure while imparting increased amorphic regions, as indicated by x-ray diffraction, for potential benefits in improved drug dissolution, bioavailability, and dosing.
KEY WORDSpolyelectrolyte complexation lipopolysaccharide PEC particulates tuberculosis mucoadhesion rifampicin
This work was supported by the National Research Foundation (NRF) of South Africa.
Compliance with Ethical Standards
The authors declare that they have no conflicts of interest.
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