The influence of lipid composition and surface charge on biodistribution of intact liposomes releasing from hydrogel-embedded vesicles.
Mixed drug delivery systems possess advantages over discrete systems, and can be used as a strategy to design more effective formulations. They are more valuable if the embedded particles perform well, rather than using drugs that have been affected by the surrounding vehicle. In order to address this concept, different liposomes have been incorporated into hydrogel to evaluate the potential effect on the controlled release of liposomes. Radiolabeled liposomes, with respect to different acyl chain lengths (DMPC, DPPC, or DSPC) and charges (neutral, negative [DSPG], or positive [DOTAP]) were integrated into chitosan-glycerophosphate. The results obtained from the biodistribution showed that the DSPC liposomes had the highest area under the curve (AUC) values, both in the blood (206.5%ID/gh(-1)) and peritoneum (622.3%ID/gh(-1)), when compared to the DPPC and DMPC formulations, whether in liposomal hydrogel or dispersion. Interesting results were observed in that the hydrogel could reverse the peritoneal retention of negatively charged liposomes, increasing to 8 times its AUC value, to attain the highest amount among all formulations. The interactions between the liposomes and chitosan-glycerophosphate, confirmed by the Fourier transform infrared (FTIR) spectra as shifted characteristic peaks, were observed in the combined systems. Overall, the hydrogel could control the release of intact liposomes, which could be manipulated by both the liposome type and interactions between the two vehicles.
Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
A
A
Alinaghi
Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: rouini@tums.ac.ir.
M R
MR
Rouini
Radioisotope Division, Nuclear Research Center, Atomic Energy Organization of Iran, Tehran, Iran.
F
F
Johari Daha
Department of Pharmaceutics, Faculty of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
H R
HR
Moghimi
D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D048271:Chitosan; D004355:Drug Stability; D005260:Female; D005994:Glycerophosphates; D020100:Hydrogels / Q000737:chemistry*; D007553:Isotope Labeling; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D010316:Particle Size; D010529:Peritoneal Cavity; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D017550:Spectroscopy, Fourier Transform Infrared; D019690:Technetium Tc 99m Exametazime / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution
D005994:Glycerophosphates; D020100:Hydrogels; D008055:Lipids; D008081:Liposomes; D019275:Radiopharmaceuticals; D019690:Technetium Tc 99m Exametazime; D048271:Chitosan
Biodistribution; IP injection; In situ forming liposomal hydrogel; Liposome charge; Liposome composition; Radiolabeled liposomes