Liposomes As A Drug Delivery Method In Cancer Immunotherapy
The future of cancer treatment is unfolding before our eyes every day. One of the more novel methods has the potential to decrease the toxicity of the drug while also having a stronger effect on tumors. Liposomes, artificially-made spherical vesicles encompassed by a lipid bilayer, possess many characteristics that are well suited for being the newest drug delivery nanotechnology. Additionally, they may be the solution to the many problems that cancer patients are faced with when treated with modern-day drugs.
Background
Lots of money, time, and science have gone into cancer research and the various kinds of treatment: the most common types being chemotherapy, radiotherapy, and surgery. Although they are overall successful measures, the health of the patient is being put at risk due to the cytotoxic effects of chemotherapy and the potential long-term degradation of tissue via radiation[1]. These effects can lead to exhaustion, diarrhea, constipation, bleeding, and much more unpleasantness for the patient. Thus, it is imperative that we test and implement methods such as Liposomes to improve the experience and health of recipients of cancer treatment.
Liposomes, discovered by Bengham in the 1960s, rapidly became a widely successful and accepted drug delivery system (DDS) in the medicine community due to its bilayer structure, hydrophobic characteristics, impressive biocompatibility, synthesizability, high drug loading efficiency, and high bioavailability [5]. The 4 categories of liposome structures allow it to be versatile in the type of cancer being treated and the molecular makeup allows endocytosis to occur extremely effectively [5]. For these reasons, the Food and Drug Administration was quick to approve Liposomes in the use of a DDS for diseases and allow clinical trials for a possible course-altering cancer treatment alternative.
Clinical trials
Many different studies on liposomes' ability to be used as a DDS for cancer treatment have been conducted and tested for many things such as the success of drug delivery, drug enhancement, liposome target accuracy, and other possible incorporations of liposomes in cancer treatment.
In 2014, the University of Oxford conducted a clinical trial in which liposomes were used as a DDS for a broad-spectrum cytotoxic agent called doxorubicin in hopes of seeing enhanced concentrations of the drug when stimulated through hyperthermia. The idea behind this trial is if this method amplifies the drug significantly more than chemotherapy does, liposomes will be a more efficient DDS. 10 patients were included in this study and all were given 50 mg/m^2 of the drug, and concentrations were then observed 24 hours after treatment. The results showed that 70% of the patients experienced a greater than two-fold increase in the amount of doxorubicin. Additionally, many of the adverse events that are generally seen in chemotherapy treatment (vomiting, nausea, swelling, pain, etc.) were minimally observed in the patients, thus alluding to it as a healthier alternative [3].
In 2019, Shandong Provincial Hospital tested the liposome's accuracy for delivering anthracyclines in lymphoma cells in hopes of finding a DDS that won’t be as toxic to the heart as the current treatment is. Being one of the most rapidly growing tumors in the world, treatment must take place immediately and efficiently with minimal risks. This tedious treatment is rigorous enough without having to worry about the restrictions that the high levels of cardiac toxicity create on the treatment, thus testing such as this is necessary. Although the results have not been released yet, the design and intention of this study mimic others that have turned out successful and further show why liposomes are needed in specific treatments such as lymphoma [2].
Finally, beyond clinical trials is all the research that goes into different solutions for specific cancers. For instance, breast, liver, prostate, lung, cervical, etc. cancer can all benefit from liposomes as their DDS for curcumin, a yellow compound derived from turmeric used in many treatments [4]. Some liposomes have even achieved the most prolonged circulation with a terminal half-life of 55 hours in humans [6]. The various methods of delivery- thin film method, thin film ultrasonic dispersion method, thin film hydration method, freeze-thawing method, etc.- are also vital in the study of liposomal-based treatment [4]. All of these subtle factors can make a world of difference when clinical trials are being pursued, thus there are many incompleted trials due to the intensity of the required research before testing takes place.
Side effects
Liposomes have exceeded many expectations in various different ways in the cancer research community. Its ability to target specific cells and reduce the toxicity of chemotherapy is just as impressive as its ability to be used in combination treatments and respond to changes in the human body. However, the more we learn and understand about liposomes, the more challenges that slowly start to surface. Some liposomes take on a passive targeting approach where they will travel via the tumor vessel and exit when they have reached the tumor. The problem with this process is it leaves pore-like holes in the vessels which may be problematic if the pore doesn’t heal as it should. Along with pores, the built-up pressure in solid tumors can inhibit equal distribution of the drug throughout the tumor and potentially induce drug resistance. Another problem with using liposomes for cancer treatment is designing the correctly sized, sustainable liposome that is capable of circulating in the bloodstream without releasing much of the drug. Liposomes respond to the body and when bound to plasma proteins, they can release up to half of their drug supply [7]. This is an unsustainable method considering how costly this process is. Treatment costs will vary depending on the complexity of the liposomes used, the stage of cancer, and other pre-existing conditions that may complicate the process [7]. As we dive deeper into liposomes and fully grasp their capabilities, we may uncover many more problems that will have to be maneuvered around in order to reach the full potential of this nanotechnology.
Conclusion
We have a long way to go in the study of liposomes if we ever hope to see them in future cancer treatments. Overcoming the obstacle of understanding a liposome's structure and its importance while manipulating it to create the desired size, shape, and functions is a complex task, but must be done in order to best maneuver tumors. The potential that liposomes possess is immense and holds a promising place in the future of cancer treatment. New technology and cancer research advancements may make liposomes a reality, but surprise conflict and increased risk may just shut liposomes down into a distant dream.
References
1. Arruebo, Manuel, et al. “Assessment of the Evolution of Cancer Treatment Therapies.” Cancers, vol. 3, no. 3, Aug. 2011, pp. 3279–330. PubMed Central, https://doi.org/10.3390/cancers3033279.
2. Clinical Application of Polyethylene Glycol Liposome Doxorubicin (PLD) in Primary Lymphoma - Full Text View - ClinicalTrials.Gov. https://clinicaltrials.gov/ct2/show/NCT02526823. Accessed 10 Aug. 2023.
3. CTG Labs - NCBI. https://www.clinicaltrials.gov/study/NCT02181075?cond=cancer&term=liposomal&intr=chemotherapy&rank=2&tab=results. Accessed 10 Aug. 2023.
4. Feng, Ting, et al. “Liposomal Curcumin and Its Application in Cancer.” International Journal of Nanomedicine, vol. 12, Aug. 2017, pp. 6027–44. PubMed Central, https://doi.org/10.2147/IJN.S132434.
5. Nsairat, Hamdi, et al. “Liposomes: Structure, Composition, Types, and Clinical Applications.” Heliyon, vol. 8, no. 5, May 2022, p. e09394. PubMed Central, https://doi.org/10.1016/j.heliyon.2022.e09394.
6. Park, John W. “Liposome-Based Drug Delivery in Breast Cancer Treatment.” Breast Cancer Research, vol. 4, no. 3, 2002, pp. 95–99. PubMed Central, https://doi.org/10.1186/bcr432.
7. Sawant, Rupa R., and Vladimir P. Torchilin. “Challenges in Development of Targeted Liposomal Therapeutics.” The AAPS Journal, vol. 14, no. 2, Mar. 2012, pp. 303–15. PubMed Central, https://doi.org/10.1208/s12248-012-9330-0.
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