The role of controlled drug release in cancer therapeutics - Dissertation Example

THE ROLE OF CONTROLLED DRUG RELEASE IN CANCER THERAPEUTICS Cancer has had different definitions. An example of these definitions is that this is a disease that affects various cells in the body of an individual by making the cells increase uncontrollably and in a rapid way. Cancer goes on produce abnormal growths in the specific part of the body that it affects which could be a breast, the lungs, the liver, the cervix, the skin or the prostate. Cancer is known to develop when a gene mutation occurs in the oncogene and suppressor genes. The cell becomes incapable of repairing its damaged DNA and undergoes programmed cell death. Cancer has the capability of spreading to other body parts through blood and lymphatic systems. It is important to note that many tumours can be cancerous but not all. Many drugs have been formulated in treatment of cancer. Alternatively, the effect of these drugs is not as expected since they have various serious side effects to the patients that rely on these drugs. These side effects were not initially expected to impact negatively on users. However, the drug efficacy is being hindered by their hydrophobic nature. Therefore, development and application of nanotechnology is one of the solutions to these blockages. (Sankhala, 2009) Nanoparticle technologies have been seen as some of the instances of technological advancements that have been implemented to assist in controlling the effects of the cancer drugs on the patients. These technologies have been implemented so as to revolutionize the development of the drug and the processes that come with it. (Lee, 2005) These technologies have been fronted to have the capacity to change the landscape seen in the field of drug production in the pharmaceutical industries. The nanoparticles are expected to deliver various relevant particles to the body parts that actually need them. Nanoparticle technology have also been optimistically expected to improve the therapeutic index that drugs have through the enhancement of efficiency only to help these drugs gain increased tolerability that can overcome any resistance that are found in the body. Nanoparticle technology could also have the capability of raising levels of availability of drugs that are water insoluble. These technologies are also responsible for the control of drug release in therapeutics because it protects therapeutic agents structurally from the physiological barriers that they could be facing. These technologies also create the development of bioactive macromolecules that are of a novel class such as the DNA. The other reason that nanoparticle technology is used for this purpose of controlled levels of drug use is that these technologies can be used to make the practitioners and the patients monitor delivery of the drugs besides the in vivo efficiency that is accredited with therapeutic agents. (Wilson, 2008) The nanotechnology was given a boost when its products were approved for clinical use by the FDA (Food and Drug Administration) based in the United States. Many of these technologies are still under pre clinic and clinic development to make them more efficient and effective for the purpose in therapy for cancer patients who need this kind of updated technologies. The nanotechnology components that have been clinically approved are majorly first generation and primarily comprise of polymer drug conjugates and liposomal drugs that are simplistic in nature. They lack the active controlled or targeting the drug release components. (Maeda, 2001) Novel nanoparticles platforms that function in various aspects of the therapy have been designed by researchers to make the nanoparticles more effective and safer for the patients to whom these kinds of treatment are applied for improved results for the patients. The treatments advocated for in this case are tissue specific; they trigger drug delivery or have the qualities to deliver synergistic combinations of drugs. Controlled drug delivery that is done in temporal and spatial manner has been considered to be critical, especially in the relevant steps in developing next generation nanotechnology commodities. When spatially managing the delivery of drugs, the success of this process can be achieved by conjugating nanoparticles that are drug encapsulated with the targeted ligands. This is important when there is the desire to facilitate preferred nanotherapeutic delivery to the intended sites while in the long run reducing side effects that are undesired and that could occur in other parts of the body. (Napier, 2007) Functionalization of the controlled drug use, made by targeting specific ligands, has facilitated controlled release of the polymeric nanoparticles responsible for releasing therapeutic agents through a regulated fashion. This approach has been received with a sigh of relief especially by those who apply the use of these medications. Some of the major classes of discussions that are presented under the focus of drug release and the relevance of its control, especially to make it easier for the cancer therapeutics to operate within the acceptable limits of the drugs include: Liposomal platforms Liposomes are multi laminar vesicles that are made from double layered membrane structures. They are often artificial and are composed of synthetic molecules known as the amphiphlic lipids which can also be natural and not necessarily artificial as the other molecules under the same platform. Liposomes act as the carriers of drug delivery qualities and they have various unique qualities that include surface modification with ease, systematic circulation with a long span of life and a favorable safety profile that attracts practitioners to this option because of the qualities it presents. The liposomal drugs were the first under nanotherapy to actually get the approval of the FDA for use in clinics. The other quality that makes the liposomal drugs more relevant for clinical application is that the liposome systems can also allow bioactive macromolecules to be delivered for therapeutic use. Liposomes that are ligand-conjugated have been seen to have the capabilities to enhance therapeutic efficiency through targeted delivery of drugs. Most of the liposomal drugs have direct effect on tumor cells especially when oxaliplatin is increased in efficiency and safety by prolonging circulation time that the drugs used before becoming fully effective. The other liposomal drug that targets the tumor cells and the Tf receptors found in them is SGT-53. The drug targets the surfaces of these tumor cells by using ligands such as that of Tf-R-scFv so as to deliver the suppressor of the genes located in the tumor. PEG carrying liposomes with loads of doxorubicin in them are sometimes coupled up with RGD so as to target integrins of vasculature tumors and have also shown signs of increasing efficiency against colon carcinoma (C26) especially in the murine model. (Gao, 2010) Liposomes that are folate-functionalized besides other liposomes such as doxorubicin have been applied in the treatment of patients who are suffering from acute myelogenous leukemia. This is because these liposomes have the characteristics that target folate receptors, specifically type-b. This idea has also given the practitioners that deal with the treatment for cancer patients the needed information that they would use when controlling drug release for the patients that have different types of cancer. Practitioners have always noted that besides the liposomes being one of the most preferred systems of drug delivery and use, the same liposomes do not always give provision for the release of major therapeutic molecules that are very significant in drug release control and this idea gives the negative vibe to this otherwise very effective nanocarrier class. (Hamaguchi, 2005) Temporal and targeted platforms of delivery through nanoparticles The different platforms that have been studied in the past with regards to nanotechnology have produced different results so as to increase the therapeutic index and pharmacological properties of the drugs used in cancer therapeutics. (Kale, 2010) The processes that these drugs are taken through help in encapsulating them, especially so as to protect them from any forms of effects that are undesired and which could be caused from external conditions. (Ganta, 2008) Polymeric nanoparticles have made significant impact on the clinical front through the improvement of pharmaceutical efficiency as well as advocating for the dosage of some of the drugs that are already clinically approved. However, it is worth noting that the polymer drugs already have their loading efficiency limited somehow because of some conjugation sites that are found in the polymer. Most of the polymer centralised drugs lack the capacity to facilitate the control of drug release. With this idea, there is an understanding that biocompatible polymeric nanoparticles are being developed so as to enhance drug loading capacities of these drugs. The polymeric micelles that are under the polymeric drug system have been given serious attention because of their extraordinary potential to act as therapeutic carriers. (Davis, 2008) Lipid polymers as seen in the hybrid nanoparticles have been motivated simply because they have integrated the specific advantages and benefits of liposome systems together with polymeric nanoparticles while at the same time overcoming their limitations. So far there are very important developments seen in the nanoparticles that have lipid polymers as their bases. Examples of such a drug are lipid coated and they comprise lipid monolayers at their interfaces. In this instance, there are PLGA cores that can carry drugs that have poor soluble qualities when taken with water and so the core that has been mentioned here makes them easier to consume for the cancer patients. Dendrimes come in handy as the other aspect that has been discussed extensively in the controlled drug system because they are synthetic macromolecules that have well defined chemical structures. They consist of initiator cores that have many layers that form terminal groups. (Chan, 2009) They have the capabilities to carry drugs through a system known as covalent conjugation to enable encapsulation especially through the hydrophobic interactions, chemical linkages, or hydrogen bonds. The dendrimers also have the ability of carrying bioactive macromolecules through condensation by electrostatic interactions for example DNA molecules. (Brigger, 2002) Control of drug release is a multifaceted process that involves several programs that should be carried out by experts so as to make it easier for the cancer patients to avoid facing difficulties when dealing with the drugs that should have the ability of reducing the effects of cancer on their livelihoods. (Alexis, 2008) Other examples in the categories of technologies such as optimal designs, surface charge, PEGylation, ligand functionalization, antibody fragments, targeting ligands, aptamers, peptides and sugars. The generation of different nanoparticles has created much enthusiasm especially for those dealing with academics on this platform and those in the drug manufacturing industries. (Farokhzad, 2006) The introduction of properties that target ligands in controlling the release property of drugs has been presented to show efficient therapeutic nanoparticles. 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