Dual Rifampicin and Isoniazid Mannose-Decorated Lipopolysaccharide Nanospheres for Macrophage- Targeted Lung Delivery.
Curr Drug Deliv
; 20(10): 1487-1503, 2023.
Article
em En
| MEDLINE
| ID: mdl-35959905
ABSTRACT
BACKGROUND:
Currently, the treatment protocols for tuberculosis (TB) have several challenges, such as inconsistent oral bioavailability, dose-related adverse effects, and off-target drug toxicity.METHODS:
This research reports the design and characterization of rifampicin (RIF) and isoniazid (INH) loaded hybrid lipid-polysaccharide nanoparticles using the solvent injection method, and demonstrated the influence of conjugated mannosyl residue on macrophage targeting and intracellular drug delivery capacity.RESULTS:
The nanospheres, herein called mannose-decorated lipopolysaccharide nanoparticles, were spherical in shape, exhibiting average sizes less than 120 nm (PDI<0.20) and positive zeta potentials. Drug encapsulation was greater than 50% for rifampicin and 60% for isoniazid. The pH-responsive drug release was sustained over a 48-hour period and preferentially released more rifampicin/isoniazid in a simulated acidic phagolysosomal environment (pH 4.8) than in a simulated physiological medium. TGA and FTIR analysis confirmed successful mannose-grafting on nanoparticle surface and optimal degree of mannosylation was achieved within 48-hour mannose-lipopolysaccharide reaction time. The mannosylated nanoparticles were biocompatible and demonstrated a significant improvement towards uptake by RAW 264.7 cells, producing higher intracellular RIF/INH accumulation when compared to the unmannosylated nanocarriers.CONCLUSION:
Overall, the experimental results suggested that mannose-decorated lipopolysaccharide nanosystems hold promise towards safe and efficacious macrophage-targeted delivery of anti-TB therapeutics.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Nanopartículas
/
Nanosferas
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Revista:
Curr Drug Deliv
Assunto da revista:
FARMACIA
/
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
África do Sul