by Keyword: Drugs

Román-Alamo, L, Avalos-Padilla, Y, Bouzón-Arnáiz, I, Iglesias, V, Fernàndez-Busquets, X, Pintado-Grima, C, Ventura, S, Fernández-Lajo, J, Monteiro, JM, Rivas, L, Fisa, R, Riera, C, Andreu, D, Arce, EM, Muñoz-Torrero, D, (2024). Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability Antimicrobial Agents And Chemotherapy ,

The problems associated with the drugs currently used to treat leishmaniasis, including resistance, toxicity, and the high cost of some formulations, call for the urgent identification of new therapeutic agents with novel modes of action. The aggregated protein dye YAT2150 has been found to be a potent antileishmanial compound, with a half-maximal inhibitory concentration (IC50) of approximately 0.5 mu M against promastigote and amastigote stages of Leishmania infantum. The encapsulation in liposomes of YAT2150 significantly improved its in vitro IC50 to 0.37 and 0.19 mu M in promastigotes and amastigotes, respectively, and increased the half-maximal cytotoxic concentration in human umbilical vein endothelial cells to >50 mu M. YAT2150 became strongly fluorescent when binding intracellular protein deposits in Leishmania cells. This fluorescence pattern aligns with the proposed mode of action of this drug in the malaria parasite Plasmodium falciparum, the inhibition of protein aggregation. In Leishmania major, YAT2150 rapidly reduced ATP levels, suggesting an alternative antileishmanial mechanism. To the best of our knowledge, this first-in-class compound is the only one described so far having significant activity against both Plasmodium and Leishmania, thus being a potential drug for the treatment of co-infections of both parasites.

JTD Keywords: Antileishmanial drugs,leishmania,protein aggregation,yat215, Axenic amastigotes,differentiation,colocalization,identification,discovery,yeas

Dirisala A, Li J, Gonzalez-Carter D, Wang Z, (2023). Editorial: Delivery systems in biologics-based therapeutics Frontiers In Bioengineering And Biotechnology 11, 1274210

Martinez-Torres S, Mesquida-Veny F, Del Rio JA, Hervera A, (2023). Injury-induced activation of the endocannabinoid system promotes axon regeneration Iscience 26, 106814

Regeneration after a peripheral nerve injury still remains a challenge, due to the limited regenerative potential of axons after injury. While the endocannabinoid system (ECS) has been widely studied for its neuroprotective and analgesic effects, its role in axonal regeneration and during the conditioning lesion remains unexplored. In this study, we observed that a peripheral nerve injury induces axonal regeneration through an increase in the endocannabinoid tone. We also enhanced the regenerative capacity of dorsal root ganglia (DRG) neurons through the inhibition of endocannabinoid degradative enzyme MAGL or a CB1R agonist. Our results suggest that the ECS, via CB1R and PI3K-pAkt pathway activation, plays an important role in promoting the intrinsic regenerative capacity of sensory neurons after injury.© 2023 The Author(s).

JTD Keywords: brain, gene-expression, lesion, nerve, receptors, targets, Clinical neuroscience, Drugs, Endogenous cannabinoid system, Molecular medicine

Roman-Alamo, L, Allaw, M, Avalos-Padilla, Y, Manca, ML, Manconi, M, Fulgheri, F, Fernandez-Lajo, J, Rivas, L, Vazquez, JA, Peris, JE, Roca-Gerones, X, Poonlaphdecha, S, Alcover, MM, Fisa, R, Riera, C, Fernandez-Busquets, X, (2023). In Vitro Evaluation of Aerosol Therapy with Pentamidine-Loaded Liposomes Coated with Chondroitin Sulfate or Heparin for the Treatment of Leishmaniasis Pharmaceutics 15, 1163

The second-line antileishmanial compound pentamidine is administered intramuscularly or, preferably, by intravenous infusion, with its use limited by severe adverse effects, including diabetes, severe hypoglycemia, myocarditis and renal toxicity. We sought to test the potential of phospholipid vesicles to improve the patient compliance and efficacy of this drug for the treatment of leishmaniasis by means of aerosol therapy. The targeting to macrophages of pentamidine-loaded liposomes coated with chondroitin sulfate or heparin increased about twofold (up to ca. 90%) relative to noncoated liposomes. The encapsulation of pentamidine in liposomes ameliorated its activity on the amastigote and promastigote forms of Leishmania infantum and Leishmania pifanoi, and it significantly reduced cytotoxicity on human umbilical endothelial cells, for which the concentration inhibiting 50% of cell viability was 144.2 ± 12.7 µM for pentamidine-containing heparin-coated liposomes vs. 59.3 ± 4.9 µM for free pentamidine. The deposition of liposome dispersions after nebulization was evaluated with the Next Generation Impactor, which mimics human airways. Approximately 53% of total initial pentamidine in solution reached the deeper stages of the impactor, with a median aerodynamic diameter of ~2.8 µm, supporting a partial deposition on the lung alveoli. Upon loading pentamidine in phospholipid vesicles, its deposition in the deeper stages significantly increased up to ~68%, and the median aerodynamic diameter decreased to a range between 1.4 and 1.8 µm, suggesting a better aptitude to reach the deeper lung airways in higher amounts. In all, nebulization of liposome-encapsulated pentamidine improved the bioavailability of this neglected drug by a patient-friendly delivery route amenable to self-administration, paving the way for the treatment of leishmaniasis and other infections where pentamidine is active.

JTD Keywords: aerosol therapy, delivery-systems, drug encapsulation, drugs, ex-vivo models, formulation, leishmania infantum, leishmania pifanoi, leishmaniasis, liposomes, macrophages, miltefosine, pentamidine, pharmacology, pulmonary absorption, visceral leishmaniasis, Amphotericin-b treatment, Leishmania infantum, Pentamidine

Tonelli M, Catto M, Sabaté R, Francesconi V, Laurini E, Pricl S, Pisani L, Miniero DV, Liuzzi GM, Gatta E, Relini A, Gavín R, Del Rio JA, Sparatore F, Carotti A, (2023). Thioxanthenone-based derivatives as multitarget therapeutic leads for Alzheimer's disease European Journal Of Medicinal Chemistry 250, 115169

A set of twenty-five thioxanthene-9-one and xanthene-9-one derivatives, that were previously shown to inhibit cholinesterases (ChEs) and amyloid β (Aβ40) aggregation, were evaluated for the inhibition of tau protein aggregation. All compounds exhibited a good activity, and eight of them (5-8, 10, 14, 15 and 20) shared comparable low micromolar inhibitory potency versus Aβ40 aggregation and human acetylcholinesterase (AChE), while inhibiting human butyrylcholinesterase (BChE) even at submicromolar concentration. Compound 20 showed outstanding biological data, inhibiting tau protein and Aβ40 aggregation with IC50 = 1.8 and 1.3 μM, respectively. Moreover, at 0.1-10 μM it also exhibited neuroprotective activity against tau toxicity induced by okadoic acid in human neuroblastoma SH-SY5Y cells, that was comparable to that of estradiol and PD38. In preliminary toxicity studies, these interesting results for compound 20 are somewhat conflicting with a narrow safety window. However, compound 10, although endowed with a little lower potency for tau and Aβ aggregation inhibition additionally demonstrated good inhibition of ChEs and rather low cytotoxicity. Compound 4 is also worth of note for its high potency as hBChE inhibitor (IC50 = 7 nM) and for the three order of magnitude selectivity versus hAChE. Molecular modelling studies were performed to explain the different behavior of compounds 4 and 20 towards hBChE. The observed balance of the inhibitory potencies versus the relevant targets indicates the thioxanthene-9-one derivatives as potential MTDLs for AD therapy, provided that the safety window will be improved by further structural variations, currently under investigation.Copyright © 2023 Elsevier Masson SAS. All rights reserved.

JTD Keywords: a? and tau aggregation inhibition, ache and bche inhibition, aggregation, alzheimer?s disease, butyrylcholinesterase, design, drugs, dual inhibitors, fibrillization, multitarget-directed ligands (mtdls), peptide, polyphenols, potent, rivatives, Ache and bche inhibition, Alzheimer's disease, Amyloid-beta, Aβ and tau aggregation inhibition, Multitarget-directed ligands (mtdls), Thioxanthene-9-one and xanthen-9-one de, Thioxanthene-9-one and xanthen-9-one derivatives

Manzano-Muñoz A, Yeste J, Ortega MA, Martín F, López A, Rosell J, Castro S, Serrano C, Samitier J, Ramón-Azcón J, Montero J, (2022). Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy Npj Precis Oncol 6, 90

Precision medicine is starting to incorporate functional assays to evaluate anticancer agents on patient-isolated tissues or cells to select for the most effective. Among these new technologies, dynamic BH3 profiling (DBP) has emerged and extensively been used to predict treatment efficacy in different types of cancer. DBP uses synthetic BH3 peptides to measure early apoptotic events ('priming') and anticipate therapy-induced cell death leading to tumor elimination. This predictive functional assay presents multiple advantages but a critical limitation: the cell number requirement, that limits drug screening on patient samples, especially in solid tumors. To solve this problem, we developed an innovative microfluidic-based DBP (µDBP) device that overcomes tissue limitations on primary samples. We used microfluidic chips to generate a gradient of BIM BH3 peptide, compared it with the standard flow cytometry based DBP, and tested different anticancer treatments. We first examined this new technology's predictive capacity using gastrointestinal stromal tumor (GIST) cell lines, by comparing imatinib sensitive and resistant cells, and we could detect differences in apoptotic priming and anticipate cytotoxicity. We then validated µDBP on a refractory GIST patient sample and identified that the combination of dactolisib and venetoclax increased apoptotic priming. In summary, this new technology could represent an important advance for precision medicine by providing a fast, easy-to-use and scalable microfluidic device to perform DBP in situ as a routine assay to identify the best treatment for cancer patients.© 2022. The Author(s).

JTD Keywords: biomarkers, cancer drugs, chemotherapy, chip, models, platform, sensitivity, strategy, tumor-cells, Precision medicine

Vukomanovic, M, Gazvoda, L, Kurtjak, M, Hrescak, J, Jaklic, B, Moya-Anderico, L, Cendra, MD, Torrents, E, (2022). Development of a ternary cyclodextrin-arginine-ciprofloxacin antimicrobial complex with enhanced stability Commun Biol 5, 1234

Designing useful functionalities in clinically validated, old antibiotics holds promise to provide the most economical solution for the global lack of effective antibiotics, as undoubtedly a serious health threat. Here we show that using the surface chemistry of the cyclodextrin (beta CD) cycle and arginine (arg) as a linker, provides more stable ternary antibiotic complex (beta CD-arg-cpx). In contrast to classical less stable inclusion complexes, which only modify antibiotic solubility, here-presented ternary complex is more stable and controls drug release. The components of the complex intensify interactions with bacterial membranes and increase the drug's availability inside bacterial cells, thereby improving its antimicrobial efficacy and safety profile. Multifunctional antibiotics, formulated as drug delivery systems per se, that take the drug to the site of action, maximize its efficacy, and provide optical detectability are envisaged as the future in fighting against infections. Their role as a tool against multiresistant strains remains as interesting challenge open for further research.; Ternary cyclodextrin- arginine- ciprofloxacin complexes show improved stability and increased efficacy against P. aeruginosa in Galleria mellonella worms.

JTD Keywords: Antibiotic-resistance, Beta-cyclodextrin, Dissolution, Drugs, Salts

Bouzon-Arnaiz, I, Avalos-Padilla, Y, Biosca, A, Cano-Prades, O, Roman-Alamo, L, Valle, J, Andreu, D, Moita, D, Prudencio, M, Arce, EM, Munoz-Torrero, D, Fernandez-Busquets, X, (2022). The protein aggregation inhibitor YAT2150 has potent antimalarial activity in Plasmodium falciparum in vitro cultures Bmc Biology 20, 197

Background By 2016, signs of emergence of Plasmodium falciparum resistance to artemisinin and partner drugs were detected in the Greater Mekong Subregion. Recently, the independent evolution of artemisinin resistance has also been reported in Africa and South America. This alarming scenario calls for the urgent development of new antimalarials with novel modes of action. We investigated the interference with protein aggregation, which is potentially toxic for the cell and occurs abundantly in all Plasmodium stages, as a hitherto unexplored drug target in the pathogen. Results Attempts to exacerbate the P. falciparum proteome's propensity to aggregation by delivering endogenous aggregative peptides to in vitro cultures of this parasite did not significantly affect their growth. In contrast, protein aggregation inhibitors clearly reduced the pathogen's viability. One such compound, the bis(styrylpyridinium) salt YAT2150, exhibited potent antiplasmodial activity with an in vitro IC50 of 90 nM for chloroquine- and artemisinin-resistant lines, arresting asexual blood parasites at the trophozoite stage, as well as interfering with the development of both sexual and hepatic forms of Plasmodium. At its IC50, this compound is a powerful inhibitor of the aggregation of the model amyloid beta peptide fragment 1-40, and it reduces the amount of aggregated proteins in P. falciparum cultures, suggesting that the underlying antimalarial mechanism consists in a generalized impairment of proteostasis in the pathogen. YAT2150 has an easy, rapid, and inexpensive synthesis, and because it fluoresces when it accumulates in its main localization in the Plasmodium cytosol, it is a theranostic agent. Conclusions Inhibiting protein aggregation in Plasmodium significantly reduces the parasite's viability in vitro. Since YAT2150 belongs to a novel structural class of antiplasmodials with a mode of action that potentially targets multiple gene products, rapid evolution of resistance to this drug is unlikely to occur, making it a promising compound for the post-artemisinin era.

JTD Keywords: amyloid pan-inhibitors, antimalarial drugs, malaria, plasmodium falciparum, protein aggregation, Amyloid formation, Amyloid pan-inhibitors, Antimalarial drugs, Colocalization, Cytosolic delivery, Derivatives, Disease, Drug, In-vitro, Malaria, Mechanism, Plasmodium falciparum, Polyglutamine, Protein aggregation, Yat2150

Biosca, A, Ramirez, M, Gomez-Gomez, A, Lafuente, A, Iglesias, V, Pozo, OJ, Imperial, S, Fernandez-Busquets, X, (2022). Characterization of Domiphen Bromide as a New Fast-Acting Antiplasmodial Agent Inhibiting the Apicoplastidic Methyl Erythritol Phosphate Pathway Pharmaceutics 14, 1320

The evolution of resistance by the malaria parasite to artemisinin, the key component of the combination therapy strategies that are at the core of current antimalarial treatments, calls for the urgent identification of new fast-acting antimalarials. The apicoplast organelle is a preferred target of antimalarial drugs because it contains biochemical processes absent from the human host. Fosmidomycin is the only drug in clinical trials targeting the apicoplast, where it inhibits the methyl erythritol phosphate (MEP) pathway. Here, we characterized the antiplasmodial activity of domiphen bromide (DB), another MEP pathway inhibitor with a rapid mode of action that arrests the in vitro growth of Plasmodium falciparum at the early trophozoite stage. Metabolomic analysis of the MEP pathway and Krebs cycle intermediates in 20 mu M DB-treated parasites suggested a rapid activation of glycolysis with a concomitant decrease in mitochondrial activity, consistent with a rapid killing of the pathogen. These results present DB as a model compound for the development of new, potentially interesting drugs for future antimalarial combination therapies.

JTD Keywords: antibiotics, antimalarial drugs, domiphen bromide, malaria, plasmodium falciparum, Antibiotics, Antimalarial drugs, Antimalarial-drug, Artemisinin, Combination therapies, Domiphen bromide, Intraerythrocytic stages, Isoprenoid biosynthesis, Malaria, Methyl erythritol phosphate pathway, Nonmevalonate pathway, Plasmodium falciparum, Plasmodium-falciparum apicoplast, Red-blood-cells, Targeted delivery

Guasch-Girbau, A, Fernandez-Busquets, X, (2021). Review of the current landscape of the potential of nanotechnology for future malaria diagnosis, treatment, and vaccination strategies Pharmaceutics 13, 2189

Malaria eradication has for decades been on the global health agenda, but the causative agents of the disease, several species of the protist parasite Plasmodium, have evolved mechanisms to evade vaccine-induced immunity and to rapidly acquire resistance against all drugs entering clinical use. Because classical antimalarial approaches have consistently failed, new strategies must be explored. One of these is nanomedicine, the application of manipulation and fabrication technology in the range of molecular dimensions between 1 and 100 nm, to the development of new medical solutions. Here we review the current state of the art in malaria diagnosis, prevention, and therapy and how nanotechnology is already having an incipient impact in improving them. In the second half of this review, the next generation of antimalarial drugs currently in the clinical pipeline is presented, with a definition of these drugs’ target product profiles and an assessment of the potential role of nanotechnology in their development. Opinions extracted from interviews with experts in the fields of nanomedicine, clinical malaria, and the economic landscape of the disease are included to offer a wider scope of the current requirements to win the fight against malaria and of how nanoscience can contribute to achieve them. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

JTD Keywords: antibody-bearing liposomes, antimalarial drugs, combination therapies, drug-delivery strategies, malaria diagnosis, malaria prophylaxis, malaria therapy, nanocarriers, nanomedicine, nanoparticles, nanotechnology, plasmodium, plasmodium-falciparum, red-blood-cells, targeted delivery, targeted drug delivery, vitro antimalarial activity, Antimalarial drugs, Isothermal amplification lamp, Malaria diagnosis, Malaria prophylaxis, Malaria therapy, Nanocarriers, Nanomedicine, Nanotechnology, Plasmodium, Targeted drug delivery

Borgheti-Cardoso, L. N., Kooijmans, S. A. A., Gutiérrez Chamorro, L., Biosca, A., Lantero, E., Ramírez, M., Avalos-Padilla, Y., Crespo, I., Fernández, I., Fernandez-Becerra, C., del Portillo, H. A., Fernàndez-Busquets, X., (2020). Extracellular vesicles derived from Plasmodium-infected and non-infected red blood cells as targeted drug delivery vehicles International Journal of Pharmaceutics 587, 119627

Among several factors behind drug resistance evolution in malaria is the challenge of administering overall doses that are not toxic for the patient but that, locally, are sufficiently high to rapidly kill the parasites. Thus, a crucial antimalarial strategy is the development of drug delivery systems capable of targeting antimalarial compounds to Plasmodium with high specificity. In the present study, extracellular vesicles (EVs) have been evaluated as a drug delivery system for the treatment of malaria. EVs derived from naive red blood cells (RBCs) and from Plasmodium falciparum-infected RBCs (pRBCs) were isolated by ultrafiltration followed by size exclusion chromatography. Lipidomic characterization showed that there were no significant qualitative differences between the lipidomic profiles of pRBC-derived EVs (pRBC-EVs) and RBC-derived EVs (RBC-EVs). Both EVs were taken up by RBCs and pRBCs, although pRBC-EVs were more efficiently internalized than RBC-EVs, which suggested their potential use as drug delivery vehicles for these cells. When loaded into pRBC-EVs, the antimalarial drugs atovaquone and tafenoquine inhibited in vitro P. falciparum growth more efficiently than their free drug counterparts, indicating that pRBC-EVs can potentially increase the efficacy of several small hydrophobic drugs used for the treatment of malaria.

JTD Keywords: Antimalarial drugs, Drug delivery, Extracellular vesicles, Malaria, Plasmodium falciparum

Lantero, E., Fernandes, J., Aláez-Versón, C. R., Gomes, J., Silveira, H., Nogueira, F., Fernàndez-Busquets, X., (2020). Heparin administered to anopheles in membrane feeding assays blocks plasmodium development in the mosquito Biomolecules 10, (8), 1136

Innovative antimalarial strategies are urgently needed given the alarming evolution of resistance to every single drug developed against Plasmodium parasites. The sulfated glycosaminoglycan heparin has been delivered in membrane feeding assays together with Plasmodium berghei-infected blood to Anopheles stephensi mosquitoes. The transition between ookinete and oocyst pathogen stages in the mosquito has been studied in vivo through oocyst counting in dissected insect midguts, whereas ookinete interactions with heparin have been followed ex vivo by flow cytometry. Heparin interferes with the parasite’s ookinete–oocyst transition by binding ookinetes, but it does not affect fertilization. Hypersulfated heparin is a more efficient blocker of ookinete development than native heparin, significantly reducing the number of oocysts per midgut when offered to mosquitoes at 5 µg/mL in membrane feeding assays. Direct delivery of heparin to mosquitoes might represent a new antimalarial strategy of rapid implementation, since it would not require clinical trials for its immediate deployment.

JTD Keywords: Anopheles, Antimalarial drugs, Heparin, Malaria, Mosquito, Ookinete, Plasmodium, Transmission blocking

Muro, Silvia, (2018). Alterations in cellular processes involving vesicular trafficking and implications in drug delivery Biomimetics 3, (3), 19

Endocytosis and vesicular trafficking are cellular processes that regulate numerous functions required to sustain life. From a translational perspective, they offer avenues to improve the access of therapeutic drugs across cellular barriers that separate body compartments and into diseased cells. However, the fact that many factors have the potential to alter these routes, impacting our ability to effectively exploit them, is often overlooked. Altered vesicular transport may arise from the molecular defects underlying the pathological syndrome which we aim to treat, the activity of the drugs being used, or side effects derived from the drug carriers employed. In addition, most cellular models currently available do not properly reflect key physiological parameters of the biological environment in the body, hindering translational progress. This article offers a critical overview of these topics, discussing current achievements, limitations and future perspectives on the use of vesicular transport for drug delivery applications.

JTD Keywords: Cellular vesicles, Vesicle fusion, Fission and intracellular trafficking, Drug delivery systems and nanomedicines, Transcytosis and endocytosis of drugs carriers, Disease effects on vesicular trafficking, Drug effects on vesicular trafficking, Role of the biological environment

Martí Coma-Cros, E., Biosca, A., Marques, J., Carol, L., Urbán, P., Berenguer, D., Riera, M. C., Delves, M., Sinden, R. E., Valle-Delgado, J. J., Spanos, L., Siden-Kiamos, I., Pérez, P., Paaijmans, K., Rottmann, M., Manfredi, A., Ferruti, P., Ranucci, E., Fernàndez-Busquets, X., (2018). Polyamidoamine nanoparticles for the oral administration of antimalarial drugs Pharmaceutics 10, (4), 225

Current strategies for the mass administration of antimalarial drugs demand oral formulations to target the asexual Plasmodium stages in the peripheral bloodstream, whereas recommendations for future interventions stress the importance of also targeting the transmission stages of the parasite as it passes between humans and mosquitoes. Orally administered polyamidoamine (PAA) nanoparticles conjugated to chloroquine reached the blood circulation and cured Plasmodium yoelii-infected mice, slightly improving the activity of the free drug and inducing in the animals immunity against malaria. Liquid chromatography with tandem mass spectrometry analysis of affinity chromatography-purified PAA ligands suggested a high adhesiveness of PAAs to Plasmodium falciparum proteins, which might be the mechanism responsible for the preferential binding of PAAs to Plasmodium-infected erythrocytes vs. non-infected red blood cells. The weak antimalarial activity of some PAAs was found to operate through inhibition of parasite invasion, whereas the observed polymer intake by macrophages indicated a potential of PAAs for the treatment of certain coinfections such as Plasmodium and Leishmania. When fluorescein-labeled PAAs were fed to females of the malaria mosquito vectors Anopheles atroparvus and Anopheles gambiae, persistent fluorescence was observed in the midgut and in other insect’s tissues. These results present PAAs as a versatile platform for the encapsulation of orally administered antimalarial drugs and for direct administration of antimalarials to mosquitoes, targeting mosquito stages of Plasmodium.

JTD Keywords: Anopheles, Antimalarial drugs, Malaria, Mosquitoes, Nanomedicine, Nanotechnology, Plasmodium, Polyamidoamines, Polymers, Targeted drug delivery

Aláez-Versón, C. R., Lantero, E., Fernàndez-Busquets, X., (2017). Heparin: New life for an old drug Nanomedicine 12, (14), 1727-1744

Heparin is one of the oldest drugs, which nevertheless remains in widespread clinical use as an inhibitor of blood coagulation. The history of its identification a century ago unfolded amid one of the most fascinating scientific controversies turning around the distribution of credit for its discovery. The composition, purification and structure-function relationship of this naturally occurring glycosaminoglycan regarding its classical role as anticoagulant will be dealt with before proceeding to discuss its therapeutic potential in, among other, inflammatory and infectious disease, cancer treatment, cystic fibrosis and Alzheimer's disease. The first bibliographic reference hit using the words 'nanomedicine' and 'heparin' is as recent as 2008. Since then, nanomedical applications of heparin have experienced an exponential growth that will be discussed in detail, with particular emphasis on its antimalarial activity. Some of the most intriguing potential applications of heparin nanomedicines will be exposed, such as those contemplating the delivery of drugs to the mosquito stages of malaria parasites.

JTD Keywords: Anopheles, Antimalarial drugs, Heparin, Malaria, Mosquitoes, Nanomedicine, Nanotechnology, Plasmodium, Targeted drug delivery

Fernàndez-Busquets, X., (2016). Novel strategies for Plasmodium-targeted drug delivery Expert Opinion on Drug Delivery , 13, (7), 919-922