Liposomal encapsulation, optimization

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... 

Harashima, H. Lida, S. Urakami, Y. Tsuchihashi, M. Kiwada, H. Optimization of antitumor effect of liposomally encapsulated doxorubicin based on simulations by pharma-cokinetic/pharmacodynamic modeling. J. Controlled Release 1999, 61 (1-2), 93-106. 

As mentioned above, the ability to adsorb to the cornea and an optimal drug release rate have been defined as the two liposomal attributes most responsible for increasing bioavailability after topical ocular administration. A number of factors, including drug encapsulation efficiency, liposome size and charge, distribution of the drug within liposomes, stability of liposomes in the conjunctival sac and ocular tissues, their retention in the conjunctival sac, and most importantly their affinity toward the corneal surface and the rate of release of the encapsulated drug, have... 

Liang W, Levchenko TS, Torchilin VP (2004) Encapsulation of ATP into liposomes by different methods Optimization of the procedure. J Microencapsul 21 251-261... 

An optimal loading procedure for doxorubicin into liposomes aims at a high drug to lipid ratio and an encapsulation efficiency of almost 100% to render the separation of unencapsulated drug unnecessary. 

ATP cannot be effectively delivered to most tissues including the ischemic myocardium without protection from degradation by plasma endonucleotidases. However, it has been established that ATP can be delivered to various tissues by its encapsulation within liposomal preparations. We describe here, the materials needed and methods used to optimize the encapsulation of ATP in liposomes, enhance their effectiveness by increasing their circulation time and target injured myocardial cells with Uposomal siufece anti-myosin antibody. Additionally, we outline methods for ex vivo studies of these ATP liposomal preparations in an isolated ischemic rat heart model and for in vivo studies of rabbits with an induced myocardial infarction. The expectation is that these methods will provide a basis for continued studies of effective ways to deliver energy substrates to the ischemic myocardium. 

We describe here, the materials needed and methods used to optimize encapsulation of ATP in liposomes, enhance their effectiveness by increasing their circulation time and target injured myocardial cells with liposomal surface anti-myosin antibody. Additionally, we outline methods for ex vivo studies in an isolated ischemic rat heart model and for in vivo studies of rabbits with an induced myocardial infarction. 

Lipid-based carriers have been established to transport DNA into cells, but the efficiency of protein delivery based on conventional liposomal formulations is below 5%. Zelphati et al., however, have developed a new lipid formulation that interacts rapidly and noncovalently with protein, creating a protective vehicle for delivery.56 The protein encapsulated in the formulation binds to the negatively charged membrane, is internalized in endosomal vesicles by endocytosis, and is then released inside the cell. The system displays no significant toxicity under optimal conditions. 

During the past few decades, numerous chemical methodologies have been developed to address drug encapsulation, retention, and stability of liposomes. Strategies or lipid stmctures that allow optimal release at the target site are just beginning to gain attention. Currently there are no such formulations in clinical trials. However,... 

Edwards, K. A., and Baeumner, A. J. (2006) Optimization of DNA-tagged dye-encapsulating liposomes for lateral-flow assays based on sandwich hybridization. Anal Bioanal Chem. 386,1335-1343... 

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