EurekaMag.com logo
+ Site Statistics
References:
53,214,146
Abstracts:
29,074,682
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Liposomal L-asparaginase: In vitro evaluation






International Journal of Pharmaceutics (Amsterdam) 96(1-3): 67-77

Liposomal L-asparaginase: In vitro evaluation

The purpose of this work was the development of liposomal formulations of L-asparaginase (L-ASNase) with the following characteristics: preservation of active enzyme, high entrapment efficiency, prolonged serum half-life and reduced toxicity compared with the free enzyme. Several liposome formulations were developed using simplified dehydration-rehydration vesicles (sDRV) or extruded vesicles (VET). The effect of lipid composition, vesicle size, ionic strength and osmolarity on enzyme encapsulation was investigated. Using a simplified dehydration-rehydration method (sDRV) we were able to achieve encapsulation efficiencies of up to 100% with full preservation (99%) of the specific activity of the encapsulated enzyme. The protein to lipid ratios of the liposomal formulations ranged from 5 to 27 mu-g/mu-mol, depending on the lipid composition. Extruded vesicles ranging from 85 to 250 nm in diameter were also tested. The encapsulation efficiency of extruded vesicles was lower than that of large vesicles and the range of preservation of specific activity was dependent on the lipid composition. Lipid combinations of phosphatidylcholine and cholesterol and either stearylamine, phosphatidylinositol or monosialoganglioside resulted in a high encapsulation efficiency (40 and 98% in VET and sDRV, respectively), high stability in saline and human serum (65-90% after 48 h) and considerable preservation of enzymatic activity (74-98%). The liposomal formulations were significantly less toxic than the free enzyme against normal CHO cells. In vivo toxicity, pharmacokinetics, biodistribution and antitumour activity studies are planned with the best formulations described in this paper.

Accession: 008961370

DOI: 10.1016/0378-5173(93)90213-y

Download PDF Full Text: Liposomal L-asparaginase: In vitro evaluation



Related references

Effects of escherichia coli asparaginase erwinia carotovora asparaginase acinetobacter glutaminase asparaginase escherichia coli asparaginase sigma pseudomonas histidase asparaginase potato phenyl alanine ammonium lyase asparaginase and mushroom tyrosinase asparaginase on human leukemic cells in vitro. Proceedings of the American Association for Cancer Research 14: 106, 1973

In vitro evaluation of the efficacy of liposomal and pegylated liposomal hydroxyurea. Indian Journal of Clinical Biochemistry 29(1): 84-88, 2014

In vivo effects of intraperitoneally injected L-asparaginase solution and L-asparaginase immobilized within semipermeable nylon microcapsules with emphasis on blood L-asparaginase, 'body' L-asparaginase, and plasma L-asparagine levels. Enzyme 18(3): 218-239, 1974

Biological characterization of L-asparaginase liposomal formulations. Cancer ChemoTherapy and Pharmacology 38(4): 373-377, 1996

A study of the in vitro effect of l asparaginase ec 1 and l asparaginase ec 2 on the glycine and nucleic acid contents in regenerating liver of albino rats. Seoul Journal Of Medicine: 257-269, 1974

Liposomal palmitoyl-L-asparaginase: Characterization and biological activity. Cancer Chemotherapy and Pharmacology 34(3): 230-234, 1994

In vitro evaluation of liposomal cyclosporine. International Journal of Pharmaceutics (Kidlington) 57(2): 133-138, 1989

Evaluation of L-asparaginase: polyethylene glycol conjugate versus native L-asparaginase combined with chemotherapy: a randomized double-blind study in canine lymphoma. Journal of Veterinary Internal Medicine 6(4): 230-234, 1992

In vitro evaluation of antibacterial of liposomal tobramycin against pseudomonas aeruginosa. Journal of Pharmacy & Pharmacology 43(SUPPL): ABSTRACT 122P, 1991

In vitro evaluation of stealth and conventional liposomal annamycin formulations. Pharmaceutical Research (New York) 13(9 SUPPL ): S164, 1996