Bioconjugates for the Drugs Delivery
The result of research in the field of drug delivery has led to the development of numerous colloidal formulations capable of optimizing the delivery of easily degradable or poorly soluble drugs. Due to their limited ability to overcome biological barriers, they are unable to reach unaltered the site of action. More recently, a new class of colloidal drug delivery systems has been designed for active drug targeting. These systems are able to recognize specific cellular and subcellular targets and accumulate in the district of action where the drug is released.
The progress of scientific research in the nanotechnology sector has led in the last fifty years to the rapid development of innovative therapeutic systems which on the one hand allow to optimize the use and performance of drugs and on the other hand to open new perspectives for the treatment of pathologies until today difficult to treat. Through the physical or chemical combination of materials with peculiar physical, biological, and biopharmaceutical characteristics, various more or less complex and sophisticated colloidal therapeutic systems have been developed. For instance, soluble polymer systems, liposomes, micelles, and lipidic or organic polymeric nanoparticles, these systems allow overcoming problems of use of drugs that have inadequate physical and biopharmaceutical characteristics, thus improving their therapeutic profile.
Over the years, numerous directed agents have been used, such as antibodies, antibody fragments, other proteins and peptides, oligonucleotides. For example, they are aptamers, oligosaccharides, and simple sugars, and small synthetic and natural organic molecules such as metabolites and vitamins. They used in the preparation of bioconjugates for active drug delivery.
Immunoconjugates and well-established antibody, hybridoma, and phage-display engineering technologies allow today to obtain monoclonal antibodies (MoAb) with high specificity and binding affinity towards selected antigens. In a short time, numerous Moab has entered therapy as such, and a large number of these protein molecules are in an advanced stage of clinical studies for the treatment of numerous pathologies. Trastuzumab (Herceptin) or rituximab, for example, have intrinsic cytotoxicity in that they interfere with molecules that stimulate cell proliferation. In combination with anticancer drugs represents a strategy to obtain a synergy between the selective and cytotoxic action of the antibody and chemotherapy drugs. Immune bioconjugates represent one of the most interesting and innovative classes of new drugs for the treatment of a wide variety of pathologies, in particular for the treatment of various tumor forms. Immunoconjugation technology allows us to significantly improve the therapeutic profile of anticancer drugs. In particular, very powerful drugs with a low therapeutic index, such as auristatin, and calicHeamicine, are excellent agents for the production of immune bioconjugates. The class of bioconjugated Immuno belongs to simple immunoconjugates in which the therapeutic agent is / or diagnostic is directly linked to the antibody, as in the case of immunoradionuclides, immune drugs, immunotoxins, immunoderivatives and more complex conjugated conjugates in which the antibody is linked to colloidal transporters. The antigen-antibody recognition is, in some cases, followed by the internalization of the bioconjugate through a clathrine dependent process. At internalization rate depends on the structure of the bioconjugate, but some studies have of.
Radioimmunoconjugates are obtained by complexing antibodies with high-energy radiation-emitting radionuclides such as beta emitters, 131iodine, and yttrium, or alpha emitters, 21bismuth and 211astatin. These bioconjugates are mainly used for hematopoietic diseases, such as lymphoma or acute myeloid leukemia, while they have proved to be not very effective in the treatment of solid tumors.
Immunotoxins are bioconjugates of internalizing antibodies with toxins of bacterial, fungal, and vegetable origin, which inactivate protein synthesis or transduction signals. , and the most used toxins are ricin, diphtheria toxin, or pseudomonas exotoxin. Ontak (Denileukin diftitox ) is a fusion protein similar to an immunotoxin obtained by the fusion of Interleukin-2 (IL-2) and diphtheria toxin and has been approved for clinical use although it has not shown high efficacy, while the side effects, such as edema, hypotension, hypoalbuminemia, and elevated liver transaminases are quite important.
immunoconjugates antibody drugs, and immunotoxins where the diagnostic and/or therapeutic agent is directly conjugated to the antibody by chemical or enzymatic way or by fusion. immunoliposomes are vesicular systems of the reservoir type which contain a high quantity of molecules of the drug (tens of thousands) and to whose surface they are tied directly or through a polymeric linker or through post-insertion MoAb antibody fragments. In addition to the ability to transport high quantities of the drug to the site of action, immuoliposomes have high avidity for the target and cellular uptake due to the presence on the surface of numerous directional molecules. On the other hand, the large dimensions (usually over 100 nm) prevent passive localization in the tumor tissue while facilitating the elimination through the endothelial reticulum system. The latter problem has been partially solved with the preparation of stealth liposomes, i.e., liposomes coated with PEG like other immunoconjugates, immunoliposomes can be internalized and release the drug into the endosome or release the drug into the extracellular matrix.
The polymers demonstrated how with these materials, it was possible to obtain systems capable of release drugs in a spatially and temporally controlled way or in specific sites of the organism with predetermined drug release kinetics. Polymer bioconjugates today represent one of the most varied and fascinating classes of pharmaceutical development, with broad development prospects for obtaining innovative systems for the active and selective delivery of drugs. Polymeric bioconjugates allow you to combine several units of drugs into a single macromolecule and combine drugs with different activities. Furthermore, polymeric bioconjugates allow improving the biopharmaceutical and pharmacokinetic profile of drugs, overcoming problems of solubility and stability of drugs, to favor the localization of drugs through passive mechanisms in solid tumors.
The technology of bioconjugation allows today to obtain new complex multifunctional supramolecular systems for directing active medication. These bioconjugates are particularly used to convey drugs to tissues and organs that are difficult to reach by drugs, such as the central nervous system, and for the delivery of molecules with a low index therapy, which can lead to high systemic toxicity. However, although the use of bioconjugates for the active direction of drugs, there are clear advantages compared to traditional pharmaceutical forms, two to the structural complexity of the development of efficient products. It requires careful and complex design and characterization. Therefore, the technological challenge that the pharmaceutical industry has called to collect in order to propose innovative therapeutic systems is the development of products that are not only effective but also simple and well-characterized easily obtainable at the industrial level with low costs.
Author: Vicki Lezama