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AAPS PharmSci. 2004 June; 6(2): 7–16.
Published online 2004 April 7. doi:  10.1208/ps060214
PMCID: PMC2751006

Acute and subchronic (28-day) oral toxicity study in rats fed with novel surfactants

Abstract

The toxicity of 2 new synthetic lipids, 1,2-dioleoyl-rac-glycerol-3-dodecaethylene glycol, GDO-12 (lipid 1) and 1,2-distearoyl-rac-glycerol-3-dodecaethylene glycol, GDS-12 (lipid 2) has been evaluated in acute and subchronic toxicity studies. Acute oral toxicity studies in male and female rats documented no deaths or treatment-related signs at high doses. The lipids were individually administered (by gavage) to male and female Sprague-Dawley rats at concentrations of 250, 500, and 1000 mg/Kg bodyweight for 28 days. All animals survived the duration of the study, with no significant changes in clinical signs, hematological parameters, organ weights, ophthalmology evaluations, or histopathological findings. These studies establish that both GDO-12 (lipid 1) and GDS-12 (lipid 2) are nontoxic in rats following oral administration. The no-observed-adverse-effect level ranged between 250 mg/Kg and 1000 mg/Kg following oral administration.

KeyWords: oral toxicity, rats, polyoxyethylene glycol (PEG), liposomes

References

1. Lasic DD. Liposomes: From Physics to Applications. Oxford, UK: Elsevier Science Ltd; 1993.
2. Hunt CA. Liposomes disposition in vivo. Liposome stability in plasma and implications for drug carrier function. Biochim Biophys Acta. 1982;719(3):450–463. [PubMed]
3. Oku N, Doi K, Namba Y, Okada S. Therapeutic effect of adriamycin encapsulated in long-circulating liposomes on meth-a-sarcoma-bearing mice. Int J Cancer. 1994;58:415–419. doi: 10.1002/ijc.2910580318. [PubMed] [Cross Ref]
4. Gabizon A. Liposome circulation time and tumor targeting: implications for cancer chemotherapy. Adv Drug Deliv Rev. 1995;16:285–294. doi: 10.1016/0169-409X(95)00030-B. [Cross Ref]
5. Gabizon A, Catane R, Uziely B, et al. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res. 1994;54:987–992. [PubMed]
6. Adlakha-Hutcheon G, Bally MB, Shew CR, Madden TD. Controlled destabilization of a liposomal drug delivery system enhances mitoxantrone antitumor activity. Nat Biotechnol. 1999;17:775–779. doi: 10.1038/11710. [PubMed] [Cross Ref]
7. Koning GA, Morselt HW, Velinova MJ, et al. Selective transfer of a lipophilic prodrug of 5-fluorodeoxyuridine from immunoliposomes to colon cancer cells. Biochim Biophys Acta. 1999;1420(1–2):153–167. [PubMed]
8. Principles for the Safety Assessment of Food Additives and Contaminant in Food International Programme on Chemical Safety (IPCS) in co-operation with the project FAO/WHO expert committee on food additives (JECFA) Rome, Italy: Food and Agriculture Organization; 1987.
9. Dacie VJ, Lewis SM. In: Practical Haematology. International student, editor. Oxford, UK: Churchill Livingstone; 1984.
10. Brij MM, Rawnsley HM. Clinical, Biochemical and Hematological Reference Values in Normal Experimental Animals. New York: Masson; 1977.
11. Harris JM, Zalipsky S. Poly(ethylene glycol) Chemistry and Biological Applications. Washington, DC: ACS Publications; 1997.
12. Lasic DD, Martin FJ. Stealth Liposomes. Boca Raton: CRC Press; 1995.
13. Keller BC, Lasic DD. Self-forming, thermodynamically stable liposomes and their applications. US patent 6 610 322, August 26, 2003.

Les articles de AAPS PharmSci ont été offerts à titre gracieux par American Association of Pharmaceutical Scientists.