mt0c00622_si_001.pdf (282.08 kB)
Targeted Delivery of Antibiotic Therapy to Inhibit Pseudomonas aeruginosa Using Lipid-Coated Mesoporous Silica Core–Shell Nanoassembly
journal contribution
posted on 2020-08-04, 16:41 authored by Kavini Rathnayake, Unnati Patel, Chi Pham, Anna McAlpin, Travis Budisalich, Surangi N. JayawardenaPseudomonas aeruginosa (PA) is an
opportunistic pathogen, which causes serious lung infections in immunocompromised
patients. Traditional oral intake of large quantities of small-molecule
antibiotics to treat bacterial infections leads to off-target toxicity
and development of drug-resistant species. Improved delivery systems
of antibiotics to the targeted site of bacterial infections would
help reduce the need for a high intake of antibiotics. Colistin (Col),
an antibacterial peptide, is considered the last resort treatment
for multidrug resistant (MDR)-PA. To approach the problem of development
of antibacterial resistance and off-target toxicity due to the use
of excessive amounts of antibiotics, we have designed a targeted drug
delivery nanoassembly, which delivers antibiotics to extracellular
and intracellular bacteria. The nanoassembly is composed of (1) drug
(Col)-loaded mesoporous silica (MSN) core (Col@MSN), (2) liposomal
shell (Col@MSN@LL), and (3) PA-targeting LL-37 peptide (Col@MSN@LL-(LL-37)).
The liposomal shell prevents premature drug release before the nanoassembly
approaches
the targeted bacteria. The liposome bilayer degrades upon excreted
lipase present in the local environment of PA, releasing encapsulated
Col. There is a significant increase in Col release (∼90% release
within 40 h) in the presence of bacteria compared to the absence of
bacteria (only ∼75% release after 80 h). A 6.7-fold increase
in the antimicrobial efficacy of Col encapsulated in Col@MSN@LL-(LL-37)
was seen compared to free Col. All studies were done using a clinical
strain of PA14. Col@MSN@LL-(LL-37) successfully targets and inhibits
intracellular PA14 within the lung epithelial cells. Only 7% PA14
viability is seen after treating the lung epithelial cells with Col@MSN@LL-(LL-37).
No significant cytotoxicity was observed with Col@MSN@LL-(LL-37).
Therefore, this discussed lipid-coated targeted nanoassembly can be
considered as a successful antibiotic delivery platform.