Drugs encapsulated in liposomes

Figure 8.14 Plasma concentrations of chemotherapy drugs encapsulated in liposomes. Curves were calculated from pharmacokinetic parameters in [2], see Table 8.6.

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. 

Numerous experimental therapeutics have shown potency in vitro however, when they are tested in vivo, they often lack significant efficacy. This is often attributed to unfavorable pharmacokinetic properties and systemic toxicity, which limit the maximum tolerated dose. These limitations can be overcome by use of drug carriers. Two general types of carrier systems have been designed drug conjugation to macromolecular carriers, such as polymers and proteins and drug encapsulation in nanocarriers, such as liposomes, polymersomes and micelles. 

In the last few decades, the discovery of SPs from natural sources with potent antiviral activities has increased significantly, but their clinical application against human viral infections is still far from being satisfactory. The therapeutic perspectives of SPs will probably improve with an adequate formulation in a clinically useful vehicle. The development of new drug delivery systems, such as encapsulation in liposomes or nanoparticles, is a strategy currently gaining attention to improve the in vivo effectiveness and reduce the adverse effects of polysulfates. The potential of these natural compounds to prevent a wide spectrum of severe viral diseases warrants further investigation to ameliorate their administration in systemic virus infections. 

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... 

The antimycotic amphotericine is encapsulated in liposomes and marketed as AmBisome to treat severe systemic mycosis. The liposomal encapsulation reduces the toxicity of amphotericine while increasing half-life of the drug and plasma level peaks. Due to stability reasons, the parenteral formulation is a lyophilized powder, which has to be reconstituted by adding the solvent just before administration. 

Fig. 6 A plot showing 50% inhibitory drug concentration in vitro, in normal and drug-resistant lines, following treatments with vinblastine solution (n), or vinblastine encapsulated in liposomes ( ). The data suggest the possibility of the reversal of drug resistance by using carrier systems like liposomes. (Adapted in part from Ref...

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