Glyconanobiotics: Novel carbohydrated nanoparticle antibiotics for MRSA and Bacillus anthracis.
This report describes the synthesis and evaluation of glycosylated polyacrylate nanoparticles that have covalently-bound antibiotics within their framework. The requisite glycosylated drug monomers were prepared from one of three known antibiotics, an N-sec-butylthio beta-lactam, ciprofloxacin, and a penicillin, by acylation with 3-O-acryloyl-1,2-O-isopropylidene-5,6 bis((chlorosuccinyl)oxy)-d-glucofuranose (7) or 6-O-acetyl-3-O-acryloyl-1,2-O-isopropylidene-5-(chlorosuccinyl)oxy-alpha-d-glucofuranose (10). These acrylated monomers were subjected to emulsion polymerization in a 7:3 (w:w) mixture of butyl acrylate-styrene in the presence of sodium dodecyl sulfate as surfactant (3 weight %) and potassium persulfate as a radical initiator (1 weight %). The resulting nanoparticle emulsions were characterized by dynamic light scattering and found to have similar diameters ( approximately 40 nm) and size distributions to those of our previously studied systems. Microbiological testing showed that the N-sec-butylthio beta-lactam and ciprofloxacin nanoparticles both have powerful in vitro activities against methicillin-resistant Staphylococcus aureus and Bacillus anthracis, while the penicillin-bound nanoparticles have no antimicrobial activity. This indicates the need for matching a suitable antibiotic with the nanoparticle carrier. Overall, the study shows that even relatively large, polar acrylate monomers (MW>1000 amu) can be efficiently incorporated into the nanoparticle matrix by emulsion polymerization, providing opportunities for further advances in nanomedicine.
Abeylath
Sampath C
SC
Center for Molecular Diversity in Drug Design, Discovery, and Delivery, Department of Chemistry, CHE 205, 4202 East Fowler Avenue, University of South Florida, Tampa, FL 33620, USA.
Turos
Edward
E
Dickey
Sonja
S
Lim
Daniel V
DV
D000179:Acrylates / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000187:drug effects*; D002241:Carbohydrates / Q000737:chemistry*; D002712:Chlorides / Q000737:chemistry; D002939:Ciprofloxacin / Q000737:chemistry; D004655:Emulsions; D016106:Methicillin Resistance / Q000187:drug effects*; D050296:Microbial Viability / Q000187:drug effects; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000179:Acrylates; D000900:Anti-Bacterial Agents; D002241:Carbohydrates; D002712:Chlorides; D004655:Emulsions; D011108:Polymers; D002939:Ciprofloxacin