Creatinine-based non-phospholipid vesicular carrier for improved oral bioavailability of Azithromycin.
BACKGROUND
Novel, safe, efficient and cost effective nano-carriers from renewable resources have got greater interest for enhancing solubility and bioavailability of hydrophobic dugs.


OBJECTIVE
This study reports the synthesis of a novel biocompatible non-phospholipid human metabolite "Creatinine" based niosomal delivery system for Azithromycin improved oral bioavailability.


METHODS
Synthesized surfactant was characterized through spectroscopic and spectrometric techniques and then the potential for niosomal vesicle formation was evaluated using Azithromycin as model drug. Drug loaded vesicles were characterized for size, polydispersity index (PDI), shape, drug encapsulation efficiency (EE), in vitro release and drug-excipient interaction using zetasizer, atomic force microscope (AFM), LC-MS/MS and FTIR. The biocompatibility of surfactant was investigated through cells cytotoxicity, blood hemolysis and acute toxicity. Azithromycin encapsulated in niosomes was investigated for in vivo bioavailability in rabbits.


RESULTS
The vesicles were spherical with 247 ± 4.67 nm diameter hosting 73.29 ± 3.51% of the drug. Surfactant was nontoxic against cell cultures and caused 5.80 ± 0.51% hemolysis at 1000 µg/mL. It was also found safe in mice up to 2.5 g/kg body weight. Synthesized surfactant based niosomal vesicles revealed enhanced oral bioavailability of Azithromycin in rabbits.


CONCLUSIONS
The results of the present study confirm that the novel surfactant is highly biocompatible and the niosomal vesicles can be efficiently used for improving the oral bioavailability of poor water soluble drugs.
a Department of Pharmacy , University of Malakand , Chakdara , Pakistan.
Shafi
S
Ullah
b International Center for Chemical and Biological Sciences , H.E.J. Research Institute of Chemistry, University of Karachi , Karachi , Pakistan.
Muhammad Raza
MR
Shah
a Department of Pharmacy , University of Malakand , Chakdara , Pakistan.
Mohammad
M
Shoaib
a Department of Pharmacy , University of Malakand , Chakdara , Pakistan.
Muhammad
M
Imran
a Department of Pharmacy , University of Malakand , Chakdara , Pakistan.
Syed Wadood Ali
SW
Shah
b International Center for Chemical and Biological Sciences , H.E.J. Research Institute of Chemistry, University of Karachi , Karachi , Pakistan.
Imdad
I
Ali
b International Center for Chemical and Biological Sciences , H.E.J. Research Institute of Chemistry, University of Karachi , Karachi , Pakistan.
Farid
F
Ahmed
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017963:Azithromycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002478:Cells, Cultured; D003404:Creatinine / Q000737:chemistry*; D016503:Drug Delivery Systems; D004355:Drug Stability; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008081:Liposomes; D051379:Mice; D010316:Particle Size; D013501:Surface-Active Agents / Q000737:chemistry
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D013501:Surface-Active Agents; D017963:Azithromycin; D003404:Creatinine
Azithromycin; Creatinine; bioavailability; niosomes; nonionic surfactant