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.
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.
Sampath C
SC
Abeylath
Edward
E
Turos
Sonja
S
Dickey
Daniel V
DV
Lim
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