Encapsulated in liposome

Subcutaneous injection of insulin encapsulated in liposomes in rats resulted in prolonged hypoglycemic effects compared to a solution of free insulin this study also indicated that a substantial fraction of hand-shaken multilamellar vesicles could enter the circulation in intact form after subcutaneous injection (Stevenson et al., 1982). The neutral liposomes used in this study were cleared more slowly from the injection site than the negatively charged liposomes. 

In view of the fact that large volumes have been administered to man without causing serious side effects (Zonneveld and Crommelin, 1988), it may be concluded that although liposomes can damage in vitro-cultured human cell lines (Nuzzo et al., 1985 Mayhew et al., 1987b), adverse effects observed in vivo are expected to be minimal. One should realize that liposomes reduce the toxicity of the encapsulated drug. Thus, the toxicity of liposomes may be of minor importance compared to the advantages of administration of certain chemotherapeutics encapsulated in liposomes. 

Data about curcunfin encapsulated in liposomes have been reported recently. The authors encapsulated curcumin into a liposomal delivery system in order to study the in vitro and in vivo effects of this compound on proliferation, apoptosis, signaling, and angiogenesis using human pancreatic carcinoma cells. Carotenoids of different polarities and in competition with cholesterol were specifically incorporated into liposomes in order to mimic the physiological uptake by cells and monitor their antioxidant capacities. ... 

Probucol, another di-r-butyl phenol, is an anti-atherosclerotic agent that can suppress the oxidation of low-density lipoprotein (LDL) in addition to lowering cholesterol levels. The antioxidant activity of probucol was measured, using EPR, with oxidation of methyl linoleate that was encapsulated in liposomal membranes or dissolved in hexane. Probucol suppressed ffee-radical-mediated oxidation. Its antioxidant activity was 17-fold less than that of tocopherol. This difference was less in liposomes than in hexane solution. Probucol suppressed the oxidation of LDL as efficiently as tocopherol. This work implies that physical factors as well as chemical reactivity are important in determining overall lipid peroxidation inhibition activity (Gotoh et al., 1992). 

Fig. 10.6 Macromolecules can also be encapsulated in liposomes. This is done by drying a mixture of liposomes and macromolecules these form polylayer structures, the macromolecules being embedded in alternating layers. Almost half the macromolecules are incorporated in liposomes on rehydration (Deamer, 1998)...

A variety of lipid adjuvants and protein mediators have also been shown to influence the immune response to antigens encapsulated in liposomes. The most widely used examples of such adjuvants for practical immunization procedures are endotoxin (including lipid A and lipopolysaccharide) and numerous types of lipophilic derivatives of muramyl dipeptide. 

The pathway of delivery seems to be an important determinant in the geno-toxicity of nickel compounds in vitro. Regarding X-chromosome fragmentation in CHO cells [306, 444], nickel chloride was reported to be ineffective by contrast to crystalline NiS. Delivery and uptake by phagocytosis of NiCl2, artificially encapsulated in liposomes, induced fragmentation. 

Maurer N, Wong KF, Hope MJ, Cullis PR. Anomalous solubility behavior of the antibiotic ciprofloxacin encapsulated in liposomes a IH-NMR study. Biochim Biophys Acta 1998 1374 9. 

Drummond DC, Marx C, Guo Z, et al. Enhanced pharmacodynamic and antitumor properties of a histone deacetylase inhibitor encapsulated in liposomes or ErbB2-targeted immunoliposomes. Clin Cancer Res 2005 11 3392-3401. Mamot C, Drummond Dc, Noble CO, et al. Epledermal growth factor receptor-targeted immunoliposomes significantly enhance the efficacy of multiple anticancer drugsin vivo. Cancer Res 2005 65 1631-1638. 

Gabizon AA, Barenholz Y, Bialer M. Prolongation of the circulation time of doxorubicin encapsulated in liposomes containing polyethylene glycol-derivatized phospholipid pharmacokinetic studies in rodents and dogs. Pharm Res 1993 10(5) 703. 

There are two major ways in which liposomes have been radiolabeled by stably trapping the radionuclide in the liposome interior (i) use of second molecule encapsulated in liposome and (ii) chemical gradient with pH or ammonium sulfate. In the first method, a radionuclide is incubated with a lipophilic chelator and then mixed with an aliquot of liposomes encapsulating a second molecule. Once the lipophilic chelator carries the radionuclide across the lipid bilayer, the second molecule interacts with the radionuclide-chelator causing the radionuclide to become trapped within the interior of the liposome. This interaction may be due to the second molecule having a higher affinity for the radionuclide than the original lipophilic chelator. An... 

Li WM, Dragowska WH, Bally MB, Schutze-Redelmeier MP. Effective induction of CD8+ T-cell response using CpG oligodeoxynucleotides and HER-2/ neu-derived peptide co-encapsulated in liposomes. Vaccine 2003 21(23) 3319-3329. 

Quenched fluorophores are encapsulated in liposomes and exposed to the inhibitors in the desired concentrations. If leakage of liposomes occurs, fluorescence intensity should increase significantly. Examples for applied markers are (i) self-quenching calcein (<60mM) (ii) HPTS (35mM) with the quencher DPX (50mM) (126,128) and (hi) 8-aminonaphthalene-l,3, 6-trisulfonic acid (ANTS) and DPX. 

Northfelt DW, Martin FJ, Working P, Volberding PA, Russell J, Newman M, Amantea MA, Kaplan LD. Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi s sarcoma. J Clin Pharmacol 1996 36 55-63. 

FIGURE 10.5 Reduction in blood glucose following pulmonary administration of 1 U/kg insulin (a), insulin encapsulated in liposomes ( ), insulin physical mixture with DPCC particles ( ). (Adapted from Mitra et al. 2001). 

Ropert, C., Malvy, C., Couvreur, P. (1993). Inhibition of the Friend retrovirus by antisense oligonucleotides encapsulated in liposomes mechanism of action. Pharm. Res., 10, 1427-1433. 

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