Liposomes drug uptake

Yatvin, M. B., Miihlensiepen, H., Porschen, W., Weinstein, J. N., and Feinendegen, L. E. (1981). Selective delivery of liposome-associated cis-dichlorodiammineplatinum(II) by heat and its influence on tumor drug uptake and growth. Cancer Res.. 41. 1602-1607. 

RES-Avoiding Liposomes. Since intravenously administered liposomes tend to accumulate in the RES, liposomal drugs work effectively when the target site is the RES. On the other hand, when the target site is not the RES, liposomal uptake by RES should be avoided. Liposomes that are not recognized by the RES have... 

Over the past 20 years, our laboratory has played a major role in the development of liposomal systems optimized for the delivery of conventional drugs, almost all of which are encapsulated by pH-gradient techniques. Our initial studies led to the development of several liposomal drug delivery systems in which uptake was driven by the citrate method of generating pH gradients (15,21-23,27,54—58). This was followed by the development of new... 

Mayer LD, Bally MB, Cullis PR, Wilson SL, Emerman JT. Comparison of free and liposome encapsulated doxorubicin tumor drug uptake and antitumor efficacy in the SCI 15 murine mammary tumor. Cancer Lett 1990 53 183. 

Drug delivery by injectable liposomes is well known in the pharmaceutical industry. Liposome suspensions of various compositions have been developed to enhance a sustained release of medications in the anterior segment of the eye, but one of the major problems in such ocular applications is limited drug uptake, because liposome suspensions are quickly washed away by tearing action. 

Matthaus, C. et aL (2008) New ways of imaging uptake and intracellular fate of liposomal drug carrier systems inside individual cells, based on Raman microscopy. MoL Pharm., 5 (2), 287-293. 

Liposomes The pH-sensitive liposomes so developed were able 56 to overcome the three main problems associated with liposomes, i.e., low stability, slow drug release and accumulation In liver/spleen. The ECM targeting liposome could prevent protein adsorption and drug leakage from liposome due to the biotin 2-PEG cross-linker located on interface of liposome. The uptake within the cancer cell is improved and could actively target tumor in tumor ECM to increase tumor accumulation. Also the drug release was enhanced at low pH, thus the potential bioavailability and drug resistance problem are also avoided. 

In conclusion, delivery of liposome-encapsulated drugs in eye drops can improve the extent of uptake and the residence time compared to the free drug. In particular, lipophilic substances seem to benefit from this approach. The exact mechanism behind the improved biopharmaceutical behavior still has to be unraveled. Intra-vitreal injection of drug-containing liposomes increases the residence times of both hydrophilic and lipophilic drugs. 

Jackson, A. J. (1981). Intramuscular absorption and regional lymphatic uptake of liposome-entrapped inulin. Drug Metab. Dispos., 9, 535-540. 

Parker, R. J., Priester, E. R., and Sieber, S. M. (1982). Comparison of lymphatic uptake metabolism, excretion, and biodistribution of free and liposome-entrapped (l cjcytosine beta-D-arabinofuranoside following intraperitoneal administration in rats, Drug. Me tab. Dispos., 10, 40-46. 

Weiner, N., and Chia-Ming Chiang (1988). Gastrointestinal uptake of liposomes, in Liposomes as Drug Carriers Recent Trends and Progress (G. Gregoriadis, ed.), John Wiley and Sons, Chichester, pp. 599-607. 

The advantageous effects of liposomal carrier systems include protection of compounds from metabolism or degradation, as well as enhanced cellular uptake. Liposome-mediated delivery of cytotoxic drugs to cells in culture has resulted in improved potency [58,59]. Prolonged release of encapsulated cargo has also been demonstrated [60,61]. More recently, liposomes with extended circulation half-lives and dose-independent pharmacokinetics (Stealth liposomes) [62] have shown promise in delivery of drugs that are normally very rapidly degraded. 

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