how can nanotechnology cure diseases
Modulating material type, shape, size and flexibility might extend vaccine durability in vivo and improve trafficking to the right biological tissues and cellular compartments. Proc. To validate the acid-mediated breakdown of the liposomes, the authors mixed two liposomal formulationsone formulation containing a fluorescence resonance energy transfer pair, and one formulation without. Solid lipid nanoparticles have been tested in rodents with the goal of improving the bioavailability of rifampicin and the combination of rifampicin, isoniazid and pyrazinamide122,123. The nanotechnology-based strategies for COVID-19 disease management include the development of tools for rapid, accurate and sensitive diagnosis, the improvement of contact tracing tools, the . These nanoparticles are produced by a novel emulsion template freeze-drying approach and have been loaded with lopinavir and efavirenz99. Miles to Go: Closing Gaps, Breaking Barriers, Righting Injustices (United Nations AIDS, 2018); http://www.unaids.org/en/resources/documents/2018/global-aids-update. Gref, R. et al. Antimicrob. To circumvent this, aqueous dispersions of nano-milled drug crystals are being developed16,17. Sundar, S. & Jaya, J. Liposomal amphotericin B and leishmaniasis: dose and response. Res. To obtain This is because this bio-coating changes important properties of the particles, including charge (positive, neutral or negative) and size. Malaria, caused by the single-celled complex protozoan of the Plasmodium genus (Fig. In the lungs and spleen of infected mice, no tubercle bacilli could be detected after five oral doses of drug-loaded solid lipid nanoparticles administered every tenth day, whereas 46 daily doses of oral free drugs were required to achieve the same therapeutic benefit123. One of these formulations was developed for the prolonged systemic delivery of dolutegravir, which has relatively high water solubility18,94. Brisbane, Queensland, Copyright 20102023, The Conversation Media Group Ltd. Nanotechnology was once the stuff of science fiction, but today the concept of creating devices and machines that are several thousand times smaller than the width of a human hair is a. Furthermore, M. tuberculosis (Fig. This is especially notable for antiretrovirals, as HIV persists in macrophages for prolonged durations, even in patients receiving antiretroviral therapy. Sci. They attributed the improved protective activity of PLGA nanoparticles to their ability to cause minimal inflammation. J. Cytol. Although liposomal drug delivery is an established platform with proven biocompatibility, the oral route of administration is typically not used due to instability in the gastrointestinal tract109. First, formulations can leak out of the vaginal tract following application of a drug delivery system. In 2017, there were 1.8 million people who became newly infected with HIV. Further research and development with affordable large-scale production is necessary for a successful malaria vaccine, and nanotechnology could play a critical role in providing new approaches to protect all ages. 36, 22 (2019). This increases the size of the injection and limits the amount of drug that can be administered. For example, when nanoparticles are injected into blood, proteins adsorb onto their surface and this can completely change their behaviour. This technology can also minimize the alreadymentioned side effects after delivering transplanted stem cells to treat liver diseases. Feng, G. et al. Melbourne, Victoria, Improving how the IMF does business could help billions of people worldwide Langer, R. & Folkman, J. Polymers for the sustained release of proteins and other macromolecules. 16, 1 (2021). The potential impact of nanotechnology on global health has long been recognised by bioengineers working in the field, and resulted in the development of numerous strategies for pathogens tracking and monitoring, drug delivery and disease prevention. Researchers will need to enable the reproducibility and bulk production while considering the environmental effects of these nanosystems. The combination therapy exhibited promising antimalarial efficacy in vivo against a resistant parasite strain113. How diseases can be targeted using nanotechnology Finally, in most clinical trials, the nanosuspensions have been administered by medical practitioners, and it is likely that patients will need to visit their caregiver for each injection. b, Low SDI countries are disproportionately affected by these top five communicable diseases. Estimated half-lives of rilpivirine and cabotegravir in nanosuspensions were 4461days (ref. The reader will glean that nanotechnology has been most actively studied in the clinic and in large animals for the treatment and prevention of HIV infection (Table 1). Pathogen resistance is a critical and ever-growing obstacle to treatment of IDs. Finally, we discuss challenges to translating these technologies from the laboratory to the clinic. Corresponding author: abbashajizade@gmail.com; abbashajizade@ihu.ac.ir"Nanotechnology-based detection, prevention and treatment of infectious diseases" Infectious diseases are a significant global concern caused by bacterial, viral, fungal, and parasitic agents, with varying levels of severity. However, upon acidification of the mixture, the liposomes disintegrated and the lipids mixed, resulting in dequenching of the fluorescence. TB is caused by the inhalation of droplet nuclei containing M. tuberculosis that enter the respiratory tract and infect the alveoli of the lungs. Mortality rates are highest in developing countries, where resources such as vaccines and anti-infectives may be limited (Fig. Nanotechnology has the potential to transform both detection and treatment of a wide range of diseases. Injectable nanocarriers are also being explored for systemic drug delivery (right). Scientists are designing materials that are a thousand times smaller than the width of a hair. The formulation of new and existing drugs in nano-sized carriers promises to overcome several challenges associated with the treatment of these diseases, including low on-target bioavailability, sub-therapeutic drug accumulation in microbial sanctuaries and reservoirs, and low patient adherence due to drug-related toxicities and extended therapeutic regimens. Correspondence to When co-administered with exogenous -lactamase, piperacillin-loaded liposomes provided twofold growth inhibition compared with the free drug co-administered with -lactamase. The FDA created a Nano Task Force in response145. In one example75, self-replicating mRNA encoding an antigen protein was complexed with a cationic dendrimer-based polymer. Pai, M. Global health technologies: time to re-think the trickle down model. Covalent attachment of heparin and monoclonal antibodies to liposomes has been proven to selectively target infected RBCs in vitro105,108. Within minutes, the sporozoites reach the liver, where they invade hepatocytes and proliferate to form merozoites. Hence, physicochemical properties of the drug and size of the drug crystals play an important role in determining drug release kinetics. Carlton, Victoria, Executive Master of Public Administration It is believed that the nanoparticles are engulfed by macrophages, leading to intracellular activation of the prodrug, followed by release of the active moiety from the macrophages18,94. Antimicrob. Targeted Intracellular delivery of antituberculosis drugs to Mycobacterium tuberculosis-infected macrophages via functionalized mesoporous silica nanoparticles. J. Pharmacol. Interestingly, the authors found the liposomes to be effective even when administered via the intravenous route. This is a highly innovative concept that may benefit from in vivo evaluation. Poor patient adherence to therapies and the need for sustained patient monitoring are major obstacles to effective treatment4. Self-assembled squalenoylated penicillin bioconjugates: an original approach for the treatment of intracellular infections. Topical drug delivery shares both challenges and therapeutic targets with pulmonary deliverybiofilm-forming opportunistic pathogens such as Staphylococcus aureus and P. aeruginosa have been implicated in both lung and skin infections. Specifically, it has been observed that the long and complex drug administration regimens needed for treatment, might lead to low patient adherence and eventually to treatment failure, especially in remote areas with limited access to health infrastructures. In a 20day efficacy study, 100% of the mice administered the peptide-functionalized nanoparticles survived, compared with roughly 40% survival in the non-functionalized-nanoparticle and free-vancomycin cohorts. 14, e1002462 (2017). Mol. J. Infect. Pharmacol. Nat. Although there was no accumulation of the dye at sites of saline injection, dye accumulation was elevated at sites of peptidase injection. The results demonstrated that while free imipenem had negligible effect when co-administered with the enzyme, the nanoparticles had comparable bactericidal effects regardless of whether carbapenemase had been co-administered. Release 162, 102110 (2012). Int. These technologies, involving systems with a diameter of about one-thousandth of the thickness of a hair, stand to substantially impact the globes main sources of morbidity and mortality. Nanocarrier systems can be designed to evade physical and chemical mechanisms for microbial drug resistance. Lancet 392, 17361788 (2018). Specifically referring to diagnostics, the authors propose that sharing protocols might enhance the impact of nanotechnology in global health; in particular, they argue that that diagnostic middleware workers, who generally run clinical laboratories in LMICs, should be able to freely access nanotechnology protocols, and modify them, using locally sourced materials and instrumentations, to adapt them to the needs of the local population. Nanomedicine: A Promising Way to Manage Alzheimer's Disease Enhanced circulation time can lead to more passes across the target and non-target tissues. The examples above highlight many promising therapeutic strategies for developing nanomedicines to treat and prevent IDs. This is important, because a nanoparticle administered to an animal experiences several levels of biological complexity on its journey from the bloodstream to the target area (see image below). PLoS ONE 8, e61135 (2013). Gentamycin was encapsulated in fusogenic liposomes that are stable under neutral conditions but disintegrate under the acidic conditions of the endolysosomes. J. Pharm. & Cheng, A. G. Mechanisms of aminoglycoside ototoxicity and targets of hair cell protection. The nanomicroparticles are a single-particle form with two nanometre-scale axes and a third of micrometre dimension. & von Reyn, C. F. Novel approaches to tuberculosis vaccine development. This resulted in improved activity over the free drug. J. Glob. Kirtane, A.R., Verma, M., Karandikar, P. et al. Leakage out of the vaginal tract was highest for uncoated nanoparticles (~13% of the dose within 0.5h). In one recent example, hydrogels filled with cells were printed onto a surface using a custom-built 3D printer. This group has shown that surface functionalization with InvA497 is beneficial for enhancing both in vitro cell uptake and antimicrobial efficacy of polymeric nanoparticles69. das Neves, J., Nunes, R., Machado, A. Kaminishi, H., Tanaka, M., Cho, T., Maeda, H. & Hagihara, Y. Activation of the plasma kallikrein-kinin system by Candida albicans proteinase. These can include designing nanocarriers to selectively target other Plasmodium stages, such as at the parasite stage in the liver or during the transmissible sexual stages. The specificity of release is unclear as even host enzymes may act as triggers. Encapsulation of drugs in nanocarriers allows for sustained drug delivery, thereby reducing dosing frequency. Fourth, the vaginal surface has several folds or rugae reducing drug accessibility. Retrov. To obtain CAS Nanotechnol.) These effects were observed with enzymes isolated from Candida albicans45, Pseudomonas aeruginosa, Aspergillus meleus and so on46. Furthermore, the accumulation of liposomes was proportional to the intensity of infection. Invest. Rev. 9, 2 (2018). Body distribution of azidothymidine bound to hexyl-cyanoacrylate nanoparticles after i.v. The uptake and intracellular accumulation of aminoglycoside antibiotics in lysosomes of cultured rat fibroblasts. As mentioned in both Reviews, the storage, distribution and administration of nanotechnologies need to be considered when designing strategies for global health, especially for diseases that predominantly impact resource-limited areas of the globe with a hot and humid climate. J. Strategies that do not rely on specific ligands have thus been dubbed passive targeting. For example, aminoglycosides largely accumulate in the lysosomes and are likely to be ineffective against cytosolic pathogens64. As such, many principles of engineering biofilm-penetrating nanosystems for pulmonary delivery can be leveraged for topical delivery. These systems have been evaluated for treating local infections of the female reproductive tract, lungs and skin. A., Lokerse, A. F., ten Kate, M. T. & Storm, G. Enhanced localization of liposomes with prolonged blood circulation time in infected lung tissue. 31, 107114 (2015). Tuberculosis 85, 415420 (2005). USA 115, E11988E11995 (2018). Curr. ACS Nano 6, 38203831 (2012). However, due to the short retention and sudden exposure to high concentrations, the treatment needs to be applied very frequently and it can be toxic to host cells40. Stimuli-sensitive nanoparticles have also been used for treatment of sepsis, where the goal was to reduce bacterial load and inflammation in the lungs62. This system is attractive for two reasonsit enabled dose reduction and the treatment of drug-resistant infection; and it dramatically reduced the number of administration events required to produce efficacy. Peer review information Nature Nanotechnology thanks the anonymous reviewers for their contribution to the peer review of this work. Pharmacokinetics of a long-acting nanoformulated dolutegravir prodrug in rhesus macaques. Duong, H. T. T. et al. Giardiello, M. et al. 532, 555572 (2017). Further testing in animal biofilm models and mechanistic confirmation must be done to reliably demonstrate the ability of nanoparticles to protect therapeutic payloads from enzymatic degradation. Sustained release of nitric oxide was achieved by fabricating nanoparticles containing reducing sugars and sodium nitrite. In contrast, the soluble drug protected only 16% of the mice from viral challenge. Transl. Find nanotechnology articles, nanomaterial data and patents all in one place. Health 4, e001719 (2019). However, further work may be required to validate this observation. Int. Modelling studies suggest that if permeability into the target tissue is greater, longer circulation times can improve targeting efficiency49. J. In these pathologies, infection does not tend to generate protective immunity, which complicates antigen identification and vaccine optimization. Q. Rev. Given that blood stage parasites are the main therapeutic target, researchers are developing various approaches to target antimalarials to infected RBCs105,106,107, thereby maximizing their therapeutic window. The highest tissue uptake was achieved with PEG-coated nanoparticles; however, tissue uptake was limited to the lower reproductive tract. Mannose-functionalized liposomes showed a 1.5-fold higher exposure in alveolar macrophages compared with unmodified liposomes. Satalkar, P., Elger, B. S., Hunziker, P. & Shaw, D. Challenges of clinical translation in nanomedicine: a qualitative study. J. Nanopart. Bakker-Woudenberg, I. Biophys. Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles. Hum. Giovanni Traverso. Release 50, 2130 (1998). Benefits of Nanotechnology for Cancer - NCI & Loboa, E. G. Skin tissue engineering for the infected wound site: biodegradable PLA nanofibers and a novel approach for silver ion release evaluated in a 3D coculture system of keratinocytes and Staphylococcus aureus. Even so, the recent regulatory success of Starpharmas VivaGel, a dendrimer antimicrobial with demonstrated efficacy against HIV, HSV and bacterial vaginosis and formulated both as gels and as a surface coating for condoms, highlight the vast potential for growth and the versatility of nanotechnological systems in this area. For this, we have developed an orally administered gastric retentive dosage form that can reduce dosing frequency from daily to weekly98. Commun. He is the Deputy Director of the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology (project number CE140100036). There is no effective vaccine that comprehensively protects against TB infection. Compared with healthy mice, the transfection efficiency of the polyplex in mice treated with lipopolysaccharide was reduced by about tenfold. The solid lines represent the mean values and the dotted lines show the uncertainty interval. Another complexity is that both drug molecules and pathogens are unevenly distributed within host cells, and in the absence of colocalization, efficacy is compromised (Fig. 3), but there is considerable room for improvement. As in many other areas, what works in the laboratory can be difficult to translate into the clinic. b, Highly polar drugs can have low uptake into cells, and drug internalized in the cell can subsequently be removed by efflux transporters. This includes investigative techniques that can complement cell and animal studies. Siegel, R. A., Kirtane, A. R. & Panyam, J. Assessing the benefits of drug delivery by nanocarriers: a partico/pharmacokinetic framework. Long-acting injectable antiretrovirals are widely considered breakthrough interventions; however, certain challenges remain. Eng. 76, 836842 (1977). In one study48, there was an ~40-fold greater liposome concentration (per cent injected dose per gram of tissue) in the abscess compared with the muscle. Release 127, 5058 (2008). Because of the prolonged and frequent dosing, and side effects, patients find it difficult to adhere to these regimens and are at risk of developing drug-resistant strains4. The authors believe that the nanoparticles are probably absorbed via the lymphatic vessels in the gastrointestinal tract. Roy, I. https://doi.org/10.1038/s41565-021-00866-8, DOI: https://doi.org/10.1038/s41565-021-00866-8. The formulation of nanomedicines for treating tuberculosis. 23, 123129 (2016). Ligand-conjugated nanocarriers can also increase their cell uptake, aiding in the treatment of intracellular pathogens. The evolution of antibiotic-degrading enzymes is a major mechanism causing bacterial resistance. Nanotechnology for diagnosis and treatment of infectious diseases This study showed excellent mechanistic details of the role of each formulation component, and the need for intracellular targeting. How nanotechnology can flick the immunity switch . and JavaScript. These fragments were 7.5% of the mass of the original antibody, which enabled them to penetrate the glycoprotein coat on the microbe and access its epitope. The half-life of the liposome-encapsulated drug in mouse lungs was about double that of the free drug (~3h versus ~1.5h). and G.T. There is only one malaria vaccine candidate that has received a positive regulatory assessment: RTS,S/AS01 (RTS,S) (Mosquirix), which is an injectable vaccine that provides partial protection against malaria in young children115. 298, 369375 (2001). Health system barriers to implementation of TB preventive strategies in South African primary care facilities. Singh, H., Jindal, S., Singh, M., Sharma, G. & Kaur, I. P. Nano-formulation of rifampicin with enhanced bioavailability: development, characterization and in-vivo safety. Ahmad, Z. However, the poor aqueous solubility of itraconzole may have precluded the pulmonary administration of the unformulated drug. Poor procurement practices, the inability to pay for drugs and poor stability of drug products at high temperature and humidity prevent access to effective treatments5. Furthermore, they found that nanoparticles were able to decrease Pseudomonas aeruginosa biofilm formation by >70% compared with untreated controls35. Sabat, E. Adherence to Long-Term Therapy: Evidence for Action (WHO, 2003). Further work in this field could be valuable. Creation of a long-acting nanoformulated dolutegravir. Chahal, J. S. et al. This third stage of the disease results in a solid caseous centre, where the bacteria can survive for years. 10, 14931503 (2015). Biomed. The Potential Benefits of Nanotechnology in Treating Alzheimer's Disease 2 Viral infections alone pose significant global health challenges by affecting millions of people worldwide, with a negative impact on both health and . Azad, A. K., Rajaram, M. V. S. & Schlesinger, L. S. Exploitation of the macrophage mannose receptor (CD206) in infectious disease diagnostics and therapeutics. Oral antiretroviral nanoparticles have been developed for paediatric use with the intent to replace tablets (which are difficult to swallow) and alcohol-containing solutions (which contain harmful excipients). Targeted delivery of antibiotics to intracellular chlamydial infections using PLGA nanoparticles. c, Coating nanocarriers with ligands that bind receptors on the surface of infected host cells (right) or pathogens (left) have also been used for increasing drug targeting. Eng. Confocal microscopy showed that only pH-sensitive liposomes released the marker intracellularly in murine macrophages. Opin. Impressively, only a single dose of the liposomal combination produced the same effect. Desai, N. Challenges in development of nanoparticle-based therapeutics. J. Infect. In mouse studies, pulmonary delivery of amorphous itraconazole nanoparticles resulted in a tenfold higher drug concentration in the lungs compared with oral administration of its commercial formulation (Sporanox) and the unformulated drug31. J. ACS Infect. 3.1. Irvine, D. J., Hanson, M. C., Rakhra, K. & Tokatlian, T. Synthetic nanoparticles for vaccines and immunotherapy. Find nanotechnology articles, nanomaterial data and patents all in one place.