drug distribution
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2022 ◽  
Vol 12 ◽  
Author(s):  
Bharti Mangla ◽  
Shamama Javed ◽  
Muhammad H. Sultan ◽  
Waquar Ahsan ◽  
Geeta Aggarwal ◽  
...  

Drug delivery using oral route is the most popular, convenient, safest and least expensive approach. It includes oral transmucosal delivery of bioactive compounds as the mucosal cavity offers an intriguing approach for systemic drug distribution. Owing to the dense vascular architecture and high blood flow, oral mucosal layers are easily permeable and can be an ideal site for drug administration. Recently, the transmucosal route is being investigated for other therapeutic candidates such as vaccines for their efficient delivery. Vaccines have the potential to trigger immune reactions and can act as both prophylactic and therapeutic conduit to a variety of diseases. Administration of vaccines using transmucosal route offers multiple advantages, the most important one being the needle-free (non-invasive) delivery. Development of needle-free devices are the most recent and pioneering breakthrough in the delivery of drugs and vaccines, enabling patients to avoid needles, reducing anxiety, pain and fear as well as improving compliance. Oral, nasal and aerosol vaccination is a novel immunization approach that utilizes a nanocarrier to administer the vaccine. Nanocarriers improve the bioavailability and serve as adjuvants to elicit a stronger immune response, resulting in increased effectiveness of vaccination. Drugs and vaccines with lower penetration abilities can also be delivered transmucosally while maintaining their biological function. The development of micro/nanocarriers for transmucosal delivery of macromolecules, vaccines and other substances is currently drawing much attention and a number of studies were performed recently. This comprehensive review is aimed to summarize the most recent investigations on needle-free and non-invasive approaches for the delivery of vaccines using oral transmucosal route, their strengths and associated challenges. The oral transmucosal vaccine delivery by nanocarriers is the most upcoming advancement in efficient vaccine delivery and this review would help further research and trials in this field.


Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 291
Author(s):  
Mariana Pereira ◽  
Nuno Vale

Drug repurposing is an emerging strategy, which uses already approved drugs for new medical indications. One such drug is gemcitabine, an anticancer drug that only works at high doses since a portion is deactivated in the serum, which causes toxicity. In this review, two methods were discussed that could improve the anticancer effect of gemcitabine. The first is a chemical modification by conjugation with cell-penetrating peptides, namely penetratin, pVEC, and different kinds of CPP6, which mostly all showed an increased anticancer effect. The other method is combining gemcitabine with repurposed drugs, namely itraconazole, which also showed great cancer cell inhibition growth. Besides these two strategies, physiologically based pharmacokinetic models (PBPK models) are also the key for predicting drug distribution based on physiological data, which is very important for personalized medicine, so that the correct drug and dosage regimen can be administered according to each patient’s physiology. Taking all of this into consideration, it is believed that gemcitabine can be repurposed to have better anticancer effects.


2022 ◽  
Author(s):  
Ruifeng Liang ◽  
Ka Hong Wong ◽  
Yan Yang ◽  
Yourong Duan ◽  
Meiwan Chen

Efficacy of photodynamic therapy (PDT) for cancer is limited due to the abnormality of tumor microenvironment (TME), such as dysfunctional tumor vascular system leading to restrict the drug distribution in...


2021 ◽  
Vol 8 (1) ◽  
pp. 3
Author(s):  
Izabela Kościk ◽  
Daniel Jankowski ◽  
Anna Jagusiak

Based on statistics from the National Cancer Institute in the US, the rate of new cases of cancer is 442.4 per 100,000 men and women per year, and more than one-third do not survive the disease. Cancer diagnosis and treatment are the most important challenges in modern medicine. The majority of cancer cases are diagnosed at an early stage. However, the possibility of simultaneous diagnosis and application of therapy (theranostics) will allow for acceleration and effectiveness of treatment. Conventional chemotherapy is not effective in reducing the chemoresistance and progression of various types of cancer. In addition, it causes side effects, which are mainly a result of incorrect drug distribution. Hence, new therapies are being explored as well as new drug delivery strategies. In this regard, nanotechnology has shown promise in the targeted delivery of therapeutics to cancer cells. This review looks at the latest advances in drug delivery-based diagnosis and therapy. Drug delivery nanosystems made of various types of carbon (graphene, fullerenes, and carbon nanotubes) are discussed. Their chemical properties, advantages, and disadvantages are explored, and these systems are compared with each other.


Marine Drugs ◽  
2021 ◽  
Vol 20 (1) ◽  
pp. 42
Author(s):  
Claire Laguionie-Marchais ◽  
A. Louise Allcock ◽  
Bill J. Baker ◽  
Ellie-Ann Conneely ◽  
Sarah G. Dietrick ◽  
...  

Phylum Cnidaria has been an excellent source of natural products, with thousands of metabolites identified. Many of these have not been screened in bioassays. The aim of this study was to explore the potential of 5600 Cnidaria natural products (after excluding those known to derive from microbial symbionts), using a systematic approach based on chemical space, drug-likeness, predicted toxicity, and virtual screens. Previous drug-likeness measures: the rule-of-five, quantitative estimate of drug-likeness (QED), and relative drug likelihoods (RDL) are based on a relatively small number of molecular properties. We augmented this approach using reference drug and toxin data sets defined for 51 predicted molecular properties. Cnidaria natural products overlap with drugs and toxins in this chemical space, although a multivariate test suggests that there are some differences between the groups. In terms of the established drug-likeness measures, Cnidaria natural products have generally lower QED and RDL scores than drugs, with a higher prevalence of metabolites that exceed at least one rule-of-five threshold. An index of drug-likeness that includes predicted toxicity (ADMET-score), however, found that Cnidaria natural products were more favourable than drugs. A measure of the distance of individual Cnidaria natural products to the centre of the drug distribution in multivariate chemical space was related to RDL, ADMET-score, and the number of rule-of-five exceptions. This multivariate similarity measure was negatively correlated with the QED score for the same metabolite, suggesting that the different approaches capture different aspects of the drug-likeness of individual metabolites. The contrasting of different drug similarity measures can help summarise the range of drug potential in the Cnidaria natural product data set. The most favourable metabolites were around 210–265 Da, quite often sesquiterpenes, with a moderate degree of complexity. Virtual screening against cancer-relevant targets found wide evidence of affinities, with Glide scores <−7 in 19% of the Cnidaria natural products.


2021 ◽  
Vol 12 ◽  
Author(s):  
Matthew S. Ellis ◽  
Zachary A. Kasper ◽  
Stephen Scroggins

Background: Stimulant use among individuals with opioid use disorder has recently increased, driven by changes in drug distribution channels. However, our understanding of polysubstance use is often limited by a need to provide targeted treatment to a primary drug of addiction. Yet there is a crucial need to better understand pathways to addiction, and how the use of multiple substances may differ between populations, as well as time periods.Methods: Using a national opioid surveillance system, we analyzed survey data from new entrants to 124 opioid use disorder treatment centers from 2017 to 2020. Age of first use was collected for prescription opioids, illicit opioids, prescription stimulants, crack/cocaine, and methamphetamines. Year of initial use of an opioid or stimulant was calculated and grouped by 5 year blocs, inclusive of initial use starting from 1991 and ending in 2020 (n = 6,048).Results: Lifetime exposure to stimulants was 82.5% among individuals with opioid use disorder. Mean age of initiation increased for all drugs in 2016–2020, in particular prescription opioids (22.3 to 31.8). Stimulants were initiating drugs for a substantial proportion of individuals with opioid use throughout the analyzed time period. Those initiating opioid/stimulant use from 1991 to 1995 had a mean average of 6.8 years between first and second drug exposure, which steadily decreased to 1.5 years between exposures in 2016–2020. Sankey plots depict significantly more drug transitions in those initiating use from 1991 to 2000 (65.1% had at least two drug transitions) compared to 2010–2020 (16.0%). Opioid-stimulant use increased over time among racial/ethnic minorities, sexual minorities, and those with an educational attainment of high school or less.Conclusion: These data highlight not only the substantial prevalence of stimulant use among individuals who develop opioid use disorder, but also the variability through which pathways of use occur. Prevention and intervention efforts need to take into account increasing ages of initial drug exposures, demographic shifts in stimulant-using populations, and more rapid drug transitions between opioid and stimulants. But at a broader level, prevention, harm reduction ideology, and addiction medicine needs to take into account the ubiquity of polysubstance use among individuals with substance use disorders.


2021 ◽  
Vol 26 (5-6) ◽  
pp. 509-538
Author(s):  
Justin Rivest

Abstract This article explores a set of medications, called les remèdes des pauvres, that were distributed from the late seventeenth century onward to the sick poor of rural France and to French missions abroad. Although it was eventually absorbed into the French state as a form of royally sponsored poor relief, this drug distribution network began in 1670 as a distinctly ecclesiastical endeavour, aimed at allowing parish priests, missionaries, and charitable laywomen to imitate the healing ministry of Christ and his apostles. While critics saw them as peddling a dangerous chemical drug in poor villages, their promoters argued that the active charity involved in distributing the remedies, and even the faith placed in their effectiveness by the sick, played an important role in effecting their cures. As such they offer a useful perspective on the shifting boundaries between medical charity and medical commerce, as well as between natural and supernatural healing.


2021 ◽  
Author(s):  
Giovanni S Offeddu ◽  
Kristina Haase ◽  
Zhengpeng Wan ◽  
Luca Possenti ◽  
Huu Tuan Nguyen ◽  
...  

Breast cancer desmoplasia heterogeneity contributes to high disease mortality due to discrepancies in treatment efficacy between patients. Personalized in vitro breast cancer models can be used for high throughput testing and ranking of therapeutic strategies to normalize the aberrant microenvironment in a patient-specific manner. Here, tumoroids assembled from patient-derived cells cultured in microphysiological systems including perfusable microvasculature reproduce key aspects of stromal and vascular dysfunction. Increased hyaluronic acid and collagen deposition, loss of vascular glycocalyx and reduced perfusion, and elevated interstitial fluid pressure in the models result in impaired drug distribution to tumor cells. We demonstrate the application of these personalized models as tools to rank molecular therapies for the normalization of the tumoroid microenvironment and to discover new therapeutic targets such as IL8 and CD44, which may ultimately improve drug efficacy in breast cancer patients.


Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1588
Author(s):  
Astrid Christine Erber ◽  
Esther Ariyo ◽  
Piero Olliaro ◽  
Patricia Nicolas ◽  
Carlos Chaccour ◽  
...  

To date, pregnant women are excluded from programmes delivering community-directed treatment of ivermectin (CDTI) for onchocerciasis and preventive chemotherapy of other helminthiases because of concerns over ivermectin safety during pregnancy. This systematic exclusion sustains an infection reservoir at the community level and deprives a vulnerable population from known benefits—there are indications that treating O. volvulus infected women may improve pregnancy outcomes and reduce the risk that their children develop onchocerciasis-associated morbidities. Furthermore, teratogenic effects are seen in non-clinical experiments at doses that far exceed those used in CDTI. Lastly, early, undetected and undeclared pregnancies are being systematically exposed to ivermectin in practice. Treatment of this population requires appropriate supporting evidence, for which we propose a three-pronged approach. First, to develop a roadmap defining the key steps needed to obtain regulatory clearance for the safe and effective use of ivermectin in all pregnant women who need it. Second, to conduct a randomised placebo-controlled double-blind clinical trial to evaluate the safety and benefits of ivermectin treatment in O. volvulus infected pregnant women. Such a trial should evaluate the possible effects of ivermectin in reducing adverse pregnancy outcomes and neonatal mortality, as well as in reducing the incidence of onchocerciasis-associated epilepsy. Third, to establish a pregnancy registry for women who inadvertently received ivermectin during pregnancy. This situation is not unique to ivermectin. Access to valuable therapies is often limited, delayed, or denied to pregnant women due to a lack of evidence. Concerns over protecting vulnerable people may result in harming them. We need to find acceptable ways to build robust evidence towards providing essential interventions during pregnancy.


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