Matryoshka-Type Gastro-Resistant Microparticles for The Oral Treatment of Mycobacterium Tuberculosis

Abstract

Aim: Production of Matryoshka-type gastroresistant microparticles containing antibiotic-loaded PLGA nanoparticles against Mycobacterium tuberculosis. Materials &methods: The emulsification and evaporation methods were followed for the synthesis of PLGA nanoparticles and methacrylic acid-ethyl acrylate-based coatings to protect rifampicin from degradation under simulated gastric conditions. Results & Conclusion:The inner antibiotic-loaded nanoparticles here reported can be released under simulated intestinal conditions whereas their coating protects them from degradation under simulated gastric conditions.The encapsulation does not hinder the antituberculosis action of the encapsulated antibiotic rifampicin. A sustained antibiotic release could be obtained when using the drug-loadedencapsulated nanoparticles.Compare to the administration of the free drug, a more effective elimination of M. tuberculosis was observed when applying the nanoparticles against infected macrophages.The antibiotic-loaded PLGA nanoparticles were also able to cross an in vitro model of intestinal barrier. Graphical abstractGraphical Abstract Description-Matryoshka-type gastroresistant microparticles containing antibiotic-loaded PLGA nanoparticles against Mycobacterium tuberculosis were produced to protect the antibiotic from degradation under simulated gastric conditions. The antibiotic-loaded PLGA nanoparticles were able to cross an in vitro model of intestinal barrier, being more effective in the elimination of M. tuberculosis when applied against infected macrophages compared to the use of the free drug.

Novel Intracellular Antibiotic Delivery System Against Staphylococcus Aureus : Cloxacillin-Loaded Poly( D , L -Lactide-Co-Glycolide) Acid Nanoparticles

“…Antimicrobial loaded NPs can offer some advantages over conventional antimicrobial treatments such as protection from clearance and enzymatic/chemical/surfactant inactivation, improved muco-adhesion and the ability to penetrate cell membranes [32,33] and biofilms [34], they present enhanced intracellular retention and improve the specific delivery to the site of infection. In the current work, we have shown that by using a single emulsion solvent evaporation technique, cloxacillin loaded PLGA NPs can be prepared with encapsulation efficiency (20.5 ± 1.2 % w/w), which is similar to what we recently demonstrated for rifampicin [17]. Using other antimicrobials, it has been previously reported that both single and double emulsion enable the preparation of drug loaded NP with high encapsulation efficiency but reduced drug loadings (DL; usually <5-10 wt.%) [35].…”

“…Empty PLGA nanoparticles had no inhibitory activity on bacterial growth in the MIC assay. However, in our previous work [17], empty PLGA-NPs showed intrinsic antituberculosis activity. This effect was attributed to the potential accelerated hydrolysis of the ester bonds of the PLGA, hence producing lactic and glycolic acids that would further acidify the media being this process autocatalytic [43].…”

Role of nanostructures in improvising oral medicine

“…The inner core bearing the antibiotic is released under specific intestinal conditions whereas the outer coating protects them from degradation. Oral administration of this drug delivery system ensures the sustained release of rifampicin and subsequent effect against Mycobacterium tuberculosis [104].…”

Controlling Particle Size and Release Kinetics in the Sustained Delivery of Oral Antibiotics Using pH-Independent Mucoadhesive Polymers

“…Some of them are pHdependent and remain protonated and insoluble in the stomach but dissolve in the intestine, others are mucoadhesive in the intestinal lining and being insoluble they erode over time providing with a time-controlled targeted release of the encapsulated active principle. We have previously encapsulated Rif within pH-dependent methacrylate-based microparticles (i.e., Eudragit® L100-55) and demonstrated their antibiotic protection against simulated gastric fluid (SGF) being the active antibiotic able to cross an in vitro model of intestinal barrier 11 . Compared to the oral administration in human subjects of the free drug and the equivalent dose of Rif encapsulated in Eudragit® S100, a superior bioavailability and sustained release were demonstrated 12 .…”