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In the 40 plus years from the concept of the clinical utility of liposomes to their recognized position in the mainstream of drug delivery systems, the path has been long and winding.
They have been explored in the clinic for applications as diverse as imaging tumors and sites of infection, for vaccine and gene medicine delivery, for treatment of infections and for cancer treatment, for lung disease and for skin conditions.
In clinical applications, liposomal drugs have been proven to be most useful for their ability to passively accumulate at sites of increased vasculature permeability, when their average diameter is in the ultrafilterable range (b200 nm in diameter), and for their ability to reduce the side effects of the encapsulated drugs relative to free drugs.
This has resulted in an overall increase in therapeutic index, which measures efficacy over toxicity.
However, the gains in therapeutic index have been more on the side of reduced toxicity than on the side of increased efficacy.
Liposomes have poor extravasation into tissues with tight endothelial junctions, and this can result in a significant reduction in the side effects of the liposomal drug compared to the free (i.e., unentrapped) drug.
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An excellent example is the significant reduction in the irreversible cardiotoxicity of free doxorubicin when the drug is entrapped in liposomes.
Most drug toxicities are reduced when they are entrapped in liposomes and the only instances in which an increase in toxicity has been noted clinically are the appearance of mucositis and the increase in a reversible form of skin toxicity called palmar plantar erthrodysesthesia (PPE) (which has been also been described for some prolonged free drug infusions), when long-circulating liposomal anthracyclines are given.
Liposomal drug delivery has become an established technology platform and has gained considerable clinical acceptance.
We can look forward to many more clinical products based on small molecule drugs in the future.
The recent remarkable success of LNP formulations of siRNA in the clinic for silencing genes in hepatocytes also indicates that the successes achieved with small molecule drugs is likely to be matched for delivery of genetic drugs such as antisense, siRNA and plasmids for gene therapy applications.
This success can be attributed in part to the remarkable flexibility of lipid-based delivery systems, which can efficiently encapsulate both small molecules and macromolecules, can be readily biodegradable and are biocompatible, can be manufactured in sizes down to 20 ?m in diameter, can payout active agents at therapeutically optimized rates, and can interact with membrane components in a predictable manner.
These properties allow a rational design approach to achieve therapeutic objectives.
The fact that all issues associated with scale-up, stability, and satisfying regulatory demands have also been successfully addressed points to a plethora of new and increasingly sophisticated lipid-based therapeutics in the future.
The Concept of the Clinical Utility of Liposomes. (2019, Nov 27). Retrieved from https://studymoose.com/the-concept-of-the-clinical-utility-of-liposomes-essay
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