Nms11176 | Healthcare Management | Assessment Answers

Give critical review on a research paper:

Development of drug-loaded immunoliposomes for the selective targeting and elimination of rosetting Plasmodium falciparum-infectedred blood cells

Answer:

Overview of main methods, results and conclusions:

Moles ert al. (2016) in their paper titled “Development of drug-loaded immunoliposomes for the selective targeting and elimination of rosetting Plasmodium falciparum-infected red blood cells” studied new strategies for the treatment for malaria which has been critically analyzed in this paper. The overall objective of this study is to assess the utility of immunoliposomal vehicle to target and eliminate rosetting Plasmodium falciperum infected red blood cells. For the study the authors performed an in vivo assay by selecting a polyclonal antibody against the NTS-DBL1α N-terminal domain within a rosetting PfEMP1 variant as the targeting molecule and lumefrantin as an antimalarial payload. Within 30 minutes of incubation with 2microns of the encapsulated drug, caused the inhibition of the parasitic forms in the culture by 70% and a 60% reduction in parasitized RBC (pRBC) with resetting phenotype. The experiment shows a potential for an innovative therapy to treat severe malaria showing a broader activity spectrum compared to anti-rosetting antibodies or free drugs (Moles et al., 2016).

Strengths of the paper:

The study uses a novel approach towards the treatment of severe malaria by selectively targeting parasitized red blood cells using immunoliposomal vehicles to carry the pharmacological agent to the target cells (Moles et al., 2016). Different studies have supported the relation between the process of resetting with the clinically severe form of malaria through the association between erythrocyte polymorphism which interferes with the resetting process and how the process can provide protection against severe malaria. However, no studies were conducted previously on how immunoliposomal vehicles can be used to transport the pharmacological agent and thereby identify and eliminate the parasitized red blood cells in severe malaria. This approach is vital for developing a new approach to cure malaria as well as develop an understanding of anti resetting immunoliposomal model, the targeting efficiency of iLP with homologous P. falciperum strains, interactions between iLP and parasitized RBC, process of iLP mediated rosette disruption and the inhibition activity of lumefrantine loaded into R29-iLPs. Such aspects therefore helps to fully understand the mechanisms through which drug loaded immunoliposomes can selectively target red blood cells infected with the malarial parasite (Johnsen et al., 2016; Eloy et al., 2017).

Usage of primary study helps to ensure accuracy of the findings as the research is directly conducted by the researchers/authors with the findings recorded in real time and first hand which ensures that it represents the reality and with no risks of alteration by other scholars. Data generated from primary findings can also be compared to findings from other similar studies using which new information or findings can be identified in the study as well as can help other researchers to duplicate the process. Primary studies can also help to avoid any biases as the findings are purely based upon the research data. Primary research also provides the researchers the ability to control the research methods such as data collection, research purpose and source of collecting the data (Collett, 2015). Due to the usage of scientific methodology, primary study also helps to from hypothesis more easily compared to secondary research. Performing the research in vitro additionally helps to conduct the research under controlled environment and therefore analyze each of the variables independently and therefore develop a better understanding of their functions and interactions. The authors were able to utilize such strengths in the study to ensure better accuracy of the results and support the credibility of the findings in a better way (Cunningham et al., 2017).

Also, the study is outlined clearly with adequate data and graphs to explain the process which provides a very clear and concise understanding of the study and its implications and potentials which are also important strengths of the study (van der Marck et al., 2017).

Weaknesses of the paper and suggestions for improvement:

One significant weakness of the study is that the results were completely based on the in vitro study in which controlled conditions were used and therefore it is vital to conduct an in vivo test for the same phenomenon. Another vital weakness of the study was that the authors did not use a control for the study to understand whether any other unknown factors could be involved in the achievement of the favorable results (Moles et al., 2016). The authors also used polyclonal antibodies raised against the resetting linked domains for the experiment; however the study could also have included monoclonal antibodies to understand how identical immune cells can react to the experiment thereby further broadening the study findings (Kisalu et al., 2018). The plasmodium culture that was used for the study was cultivated in blood group O RBC and malarial culture medium that is supplemented with human AB+ serum following the standard procedure. However, the researchers could have also used AB type RBC in order to understand the interaction with the surface domains of the cell with the immune molecules and thereby get more data from the process (Ch’ng et al., 2016). The authors did not compare the usage of gold nanoparticles for the targeted delivery of the drug to the target cells which has been extensively used for drug delivery in several studies.

In order to improve these weaknesses, the following strategies can be used:

• Using an in vivo study in the experiment
• Using a research control
• Using monoclonal antibodies
• Using AB blood type RBC
• Using gold nanoparticles for drug delivery

(Ch’ng et al., 2016; Kisalu et al., 2018)

Further studies/unanswered questions:

The study provides important information regarding the utility of drug loaded immunoliposomes for treating severe malaria, providing a new approach for the treatment (Moles et al., 2016). The authors pointed out that the NTS-DBL1α domain of PfEMP1 is one of the key mediators of resetting and antibodies raised against this region can help to prevent the formation of rosettes. However, the study did not consider the utility of gold nanoparticles for the delivery of the drug which could be compared with the efficiency of the immunoliposomes in the experiment (Johnsen et al., 2016). The study also did not clarify how the formation of rosettes can be influenced by antibodies raised from AB type RBC.

References:

Ch’ng, J. H., Moll, K., del Pilar Quintana, M., Chan, S. C. L., Masters, E., Moles, E., ... & Wahlgren, M. (2016). Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications. Scientific reports, 6, 29317.

Collett, D. (2015). Modelling survival data in medical research. Chapman and Hall/CRC.

Cunningham, D., Stenning, S. P., Smyth, E. C., Okines, A. F., Allum, W. H., Rowley, S., ... & Griffin, S. M. (2017). Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2–3 trial. The Lancet Oncology, 18(3), 357-370.

Eloy, J. O., Petrilli, R., Chesca, D. L., Saggioro, F. P., Lee, R. J., & Marchetti, J. M. (2017). Anti-HER2 immunoliposomes for co-delivery of paclitaxel and rapamycin for breast cancer therapy. European Journal of Pharmaceutics and Biopharmaceutics, 115, 159-167.

Johnsen, K. B., Larsen, A. B., Bruun, J., Siupka, P., Nielsen, M. S., Andresen, T. L., & Moos, T. (2016). Targeting immunoliposomes to transferrin receptors on brain capillary endothelial cells as a mean for cargo transport across the blood-brain barrier. In 19th International Symposium on Signal Transduction at the Blood-Brain Barriers. University of Copenhagen.

Kisalu, N. K., Idris, A. H., Weidle, C., Flores-Garcia, Y., Flynn, B. J., Sack, B. K., ... & Miller, A. B. (2018). A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite. Nature medicine, 24(4), 408.

Moles, E., Moll, K., Ch'ng, J. H., Parini, P., Wahlgren, M., & Fernàndez-Busquets, X. (2016). Development of drug-loaded immunoliposomes for the selective targeting and elimination of rosetting Plasmodium falciparum-infected red blood cells. Journal of Controlled Release, 241, 57-67.

van der Marck, M. A., Melis, R. J., & Rikkert, M. G. O. (2017). On evidence-based medicine. The Lancet, 390(10109), 2244-2245.