Ascorbyl palmitate vesicles (Aspasomes): formation, characterization and applications

• Published in: International journal of pharmaceutics 2004-03, Vol.271 (1), p.95-113
• Main Authors: Gopinath, D, Ravi, D, Rao, B.R, Apte, S.S, Renuka, D, Rambhau, D
• Format: Article
• Language: English
• Subjects: Animals; Antioxidant potency; Antioxidants - administration & dosage; Antioxidants - chemistry; Antioxidants - pharmacokinetics; Ascorbic Acid - analogs & derivatives; Ascorbic Acid - chemistry; Ascorbyl palmitate; Ascorbyl palmitate vesicles; Aspasomes; Azidothymidine (AZT); Biological and medical sciences; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Cholesterol - chemistry; Drug Carriers - chemistry; Drug Stability; DSC; General pharmacology; In Vitro Techniques; Lipid Bilayers - chemistry; Lipid Peroxidation; Lipoperoxidation of blood in vitro; Medical sciences; Niosomes; Organophosphates - chemistry; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rats; Release; Skin Absorption; Solubility; Transdermal permeation; Zidovudine - administration & dosage; Zidovudine - chemistry; Zidovudine - pharmacokinetics
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2003.10.032

Vesicles with biological activity or with a targeting function in addition to carrier properties will have an added advantage. Vesicles prepared with amphiphiles having antioxidant property may have potential applications towards disorders implicated with reactive oxygen species. Ascorbyl palmitate (ASP) was explored as bilayer vesicle forming material. It formed vesicles (Aspasomes) in combination with cholesterol and a negatively charged lipid (dicetyl phosphate). Aspasomes were prepared by film hydration method followed by sonication in which aqueous azidothymidine (AZT) solution was encapsulated in aqueous regions of bilayer. Aspasomes were obtained with all compositions containing 18–72 mol% cholesterol. Differential scanning calorimetric data of aspasome dispersion and anhydrous mixtures of ascorbyl palmitate, cholesterol and dicetyl phosphate confirm the formation of bilayered vesicles with ascorbyl palmitate. Cholesterol content in aspasome did not exhibit any relation with vesicle size, zeta potential or percent entrapment. A substantial change in release rate of azidothymidine from aspasome was noticed on varying the proportion of cholesterol. Release rate and cholesterol content in Aspasomes did not exhibit any relation. A preparation with 45 mol% of cholesterol showed maximum retardation in release rate, than other compositions. The change in capture volume with time (latency) was studied for 8 h and with such a short duration study it was difficult to predict long term stability of these vesicles. But release experiments do indicate stability upto 18 h. Percent reducing activity of aspasome was estimated by measuring the absorbance of α,α-diphenyl-β-picrylhydrazyl (DPPH) at 517 nm after addition of test antioxidant samples. These studies revealed that the antioxidant potency of ascorbyl moiety is retained even after converting ascorbyl palmitate into vesicles (Aspasomes). The antioxidant potency of Aspasomes was assessed by measuring the protection offered by this preparation against quinolinic acid induced lipoperoxidation of whole human blood in vitro, where in the lipoperoxidation was monitored by measuring thiobarbituric acid reactive substances (TBARS) levels. Aspasome rendered much better antioxidant activity than ascorbic acid. Transdermal permeation of aspasomal AZT, ASP-AZT aqueous dispersion and AZT-solution across excised rat skin was investigated in vitro using Franz diffusion cell. Permeation of aspasomal AZT was much higher than