title: Ciprofloxacin surf-plexes in sub-micron emulsions: a novel approach to improve payload efficiency and antimicrobial efficacy.
abstract: The aim of this study was to investigate antimicrobial efficacy and pharmacokinetic profile of ciprofloxacin (CFn) loaded oil-in-water (o/w) submicron emulsion (SE-CFn). This study emphasized on development of hydrophobic ion-pair complexes of CFn with sodium deoxycholate (SDC) [CFn-SDC], which was incorporated in the core of SE (SE-CFn-SDC). SE-CFn-SDC was characterized for globulet size (278±12 nm), zeta potential (-25.3±1 mV), viscosity (2.6±0.3 cP), transmission electron microscopy (TEM), drug entrapment and for in vitro release profile. The entrapment efficiency (EE) was significantly improved (≥80%; p≤0.05) on ion-pairing while it was merely 27.2±3.1% for free CFn. The cytotoxicity studies of formulations on J774 macrophage cells showed that more than 90±3% of cells were viable, even at high concentration (100 μg/ml). SE-CFn-SDC was further modified with cationic inducer chitosan (SE-CH-CFn-SDC), which showed almost twofold and fourfold enhancement in antimicrobial efficacy as compared to SE-CFn-SDC and SE-CFn, respectively when tested in vitro against E. coli, S. aureus, and P. aeruginosa. When tested in male Balb/c mice, the AUC(0-24h) of SE-CH-CFn-SDC (23.27±2.8 h μg/ml) was found to be 1.7-fold and 5-fold higher as compared to SE-CFn-SDC (13.17±0.88 h μg/ml) and CFn solution (4.70±0.77 h μg/ml), respectively. The study demonstrates that surfactant based ionic complex formation incorporated in surface modified submicron emulsion is a promising approach to improve payload efficiency of poorly water soluble drugs with improved antimicrobial efficacy and pharmacokinetic profile.
authors.affiliation: Pharmaceutics Division, Central Drug Research Institute (CSIR), Lucknow, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Jain
authors.forename: Deepak
authors.initials: D
authors.lastname: Singodia
authors.forename: Girish K
authors.initials: GK
authors.lastname: Gupta
authors.forename: Durga
authors.initials: D
authors.lastname: Garg
authors.forename: G B Shiva
authors.initials: GB
authors.lastname: Keshava
authors.forename: Rahul
authors.initials: R
authors.lastname: Shukla
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Shukla
authors.forename: Prabhat R
authors.initials: PR
authors.lastname: Mishra
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000737:chemistry*; D004655:Emulsions; D004926:Escherichia coli / Q000187:drug effects; D005079:Excipients / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013501:Surface-Active Agents / Q000737:chemistry*; D014783:Viscosity
chemical_list: D000890:Anti-Infective Agents; D004655:Emulsions; D005079:Excipients; D013501:Surface-Active Agents; D003840:Deoxycholic Acid; D002939:Ciprofloxacin; D048271:Chitosan