Design of novel proliposome formulation for antioxidant peptide, glutathione with enhanced oral bioavailability and stability
| Autor: | Sang-Eun Lee, Jong Chan Byeon, Jeong-Sook Park, Jung Bin Ahn, Jin-Seok Choi, Tae-Hyeon Kim, Dong-Hyun Kim |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Antioxidant medicine.medical_treatment Chemistry Pharmaceutical Pharmaceutical Science Administration Oral Biological Availability Peptide 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy Antioxidants KB Cells Excipients Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Delivery Systems Cell Line Tumor medicine Animals Humans Particle Size glutathione oral drug delivery system chemistry.chemical_classification Drug Carriers Chemistry Granule (cell biology) lcsh:RM1-950 peptide drug General Medicine Glutathione 021001 nanoscience & nanotechnology Lipids Bioavailability Rats lcsh:Therapeutics. Pharmacology Solubility Liposomes proliposome Mannitol 0210 nano-technology Peptide drug Peptides medicine.drug Research Article |
| Zdroj: | Drug Delivery, Vol 26, Iss 1, Pp 216-225 (2019) Drug Delivery |
| DOI: | 10.6084/m9.figshare.7813580.v1 |
| Popis: | To develop proliposome formulations to improve the oral bioavailability of l-glutathione (GSH), GSH-loaded proliposomes were prepared using the granule method. Mannitol was selected as an effective excipient to achieve the desired particle size, entrapment efficiency (EE), and solubility for oral delivery of the final formulation. To evaluate the effect of surface charge of proliposomes on the oral bioavailability of GSH, negative (F1–F4) and positive proliposomes (F5–F9) were prepared. Particle size of F1 and F5 was 167.8 ± 0.9 and 175.9 ± 2.0 nm, and zeta potential of F1 and F5 was –8.1 ± 0.7 and 21.1 ± 2.0 mV, respectively. Encapsulation efficiency of F1 and F5 was 58.6% and 54.7%, respectively. Considering their particle size, zeta potential, and EE, the proliposomes F1 and F5 were adopted as the optimal formulations for further experiments. Solid state characterization of the proliposomes confirmed lipid coating on the surface of mannitol. The release of GSH from F1 and F5 formulations was prolonged until 24 h and pH independent. The total antioxidant capacity of GSH was concentration-dependent and maintained after formulation of GSH proliposomes. Circular dichroism spectroscopy confirmed that the molecular structure of GSH was maintained in the proliposome formulations. GSH proliposomes exhibited no significant changes in particle size and zeta potential for 4 weeks. An oral bioavailability study in rats revealed that F5 exhibited 1.05-, 1.08-, and 1.11-fold higher bioavailability than F1, commercial capsule formulation, and pure GSH, respectively. In conclusion, the prepared GSH proliposomes enhanced the poor bioavailability of GSH and prolonged its duration of action. |
| Databáze: | OpenAIRE |
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