Lipase-sensitive polymeric triple-layered nanogel for "on-demand" drug delivery.
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.
CAS Key Laboratory of Soft Matter Chemistry and Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China.
Meng-Hua
MH
Xiong
Yan
Y
Bao
Xian-Zhu
XZ
Yang
Yu-Cai
YC
Wang
Baolin
B
Sun
Jun
J
Wang
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D008049:Lipase / Q000737:chemistry / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry* / Q000378:metabolism; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D000080385:Nanogels; D011108:Polymers; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D014640:Vancomycin; D011094:Polyethyleneimine; D008049:Lipase