Lipase-sensitive polymeric triple-layered nanogel for "on-demand" drug delivery.
J Am Chem Soc
; 134(9): 4355-62, 2012 Mar 07.
Article
en En
| MEDLINE
| ID: mdl-22304702
ABSTRACT
We report a new strategy for differential delivery of antimicrobials to bacterial infection sites with a lipase-sensitive polymeric triple-layered nanogel (TLN) as the drug carrier. The TLN was synthesized by a convenient arm-first procedure using an amphiphilic diblock copolymer, namely, monomethoxy poly(ethylene glycol)-b-poly(ε-caprolactone), to initiate the ring-opening polymerization of the difunctional monomer 3-oxapentane-1,5-diyl bis(ethylene phosphate). The hydrophobic poly(ε-caprolactone) (PCL) segments collapsed and surrounded the polyphosphoester core, forming a hydrophobic and compact molecular fence in aqueous solution which prevented antibiotic release from the polyphosphoester core prior to reaching bacterial infection sites. However, once the TLN sensed the lipase-secreting bacteria, the PCL fence of the TLN degraded to release the antibiotic. Using Staphylococcus aureus (S. aureus) as the model bacterium and vancomycin as the model antimicrobial, we demonstrated that the TLN released almost all the encapsulated vancomycin within 24 h only in the presence of S. aureus, significantly inhibiting S. aureus growth. The TLN further delivered the drug into bacteria-infected cells and efficiently released the drug to kill intracellular bacteria. This technique can be generalized to selectively deliver a variety of antibiotics for the treatment of various infections caused by lipase-secreting bacteria and thus provides a new, safe, effective, and universal approach for the treatment of extracellular and intracellular bacterial infections.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
/
Polietileneimina
/
Polímeros
/
Portadores de Fármacos
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Sistemas de Liberación de Medicamentos
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Lipasa
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
J Am Chem Soc
Año:
2012
Tipo del documento:
Article
País de afiliación:
China