Extended nasal residence time of lysostaphin and an anti-staphylococcal monoclonal antibody by delivery in semisolid or polymeric carriers.
OBJECTIVE
Eradication of Staphylococcus aureus nasal colonization reduces the risk of nosocomial and community acquired infections with this organism. This study describes the formulation and use of lysostaphin and BSYX-A110, an anti-lipoteichoic acid monoclonal antibody, for eradication of S. aureus nasal colonization.


METHODS
Lysostaphin was formulated into a hydrophilic cream that forms an emulsion with the secretions of the nasal mucosa, and aqueous formulations of BSYX-A110 were made containing the mucoadhesive polymers polystyrene sulfonate and chitosan. Intranasal pharmacokinetics of the drugs was measured in mice and cotton rats.


RESULTS
Lysostaphin formulated in the cream increased nasal retention of the drug by 10-fold at 3 h post-cream installation and 50-fold at 24 h as compared to lysostaphin in saline drops. Furthermore, the levels of lysostaphin in the nose 24 h post-cream instillation are still above the minimum bactericidal concentration for most bacterial strains. The liquid polymer formulations also resulted in prolonged retention of antibody in the nose, with 4-fold higher levels at 3 h post-instillation as compared to antibody in saline drops.


CONCLUSIONS
These results demonstrate that cream and polymer delivery systems significantly decrease the clearance rate of lysostaphin and BSYX-A110 from the nose, thereby enhancing their therapeutic potential for eradicating S. aureus nasal colonization.
Walsh
Scott
S
Biosynexus, Inc., Gaithersburg, Maryland 20877, USA. scottwalsh@biosynexus.com
Kokai-Kun
John
J
Shah
Anjali
A
Mond
James
J
D000281:Administration, Intranasal; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D048271:Chitosan; D004337:Drug Carriers; D004338:Drug Combinations; D016503:Drug Delivery Systems; D005260:Female; D008248:Lysostaphin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051379:Mice; D008813:Mice, Inbred ICR; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D009824:Ointments; D011108:Polymers; D051381:Rats; D016205:Sigmodontinae; D013211:Staphylococcus aureus / Q000276:immunology*
D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D004338:Drug Combinations; D009824:Ointments; D011108:Polymers; D048271:Chitosan; D008248:Lysostaphin