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Advanced Drug Delivery Reviews Nov 2023Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical... (Review)
Review
Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical excipients, food additives, emulsifiers in cosmetics, and as household/industrial detergents. This review outlines the interaction of surfactant-type excipients present in oral pharmaceutical dosage forms with the intestinal epithelium of the gastrointestinal (GI) tract. Many surfactants permitted for human consumption in oral products reduce intestinal epithelial cell viability in vitro and alter barrier integrity in epithelial cell monolayers, isolated GI tissue mucosae, and in animal models. This suggests a degree of mis-match for predicting safety issues in humans from such models. Recent controversial preclinical research also infers that some widely used emulsifiers used in oral products may be linked to ulcerative colitis, some metabolic disorders, and cancers. We review a wide range of surfactant excipients in oral dosage forms regarding their interactions with the GI tract. Safety data is reviewed across in vitro, ex vivo, pre-clinical animal, and human studies. The factors that may mitigate against some of the potentially abrasive effects of surfactants on GI epithelia observed in pre-clinical studies are summarised. We conclude with a perspective on the overall safety of surfactants in oral pharmaceutical dosage forms, which has relevance for delivery system development.
Topics: Animals; Humans; Excipients; Drug Compounding; Pharmaceutical Preparations; Intestines; Surface-Active Agents
PubMed: 37739041
DOI: 10.1016/j.addr.2023.115086 -
Pharmaceutical Research May 2024Currently, the lengthy time needed to bring new drugs to market or to implement postapproval changes causes multiple problems, such as delaying patients access to new...
Currently, the lengthy time needed to bring new drugs to market or to implement postapproval changes causes multiple problems, such as delaying patients access to new lifesaving or life-enhancing medications and slowing the response to emergencies that require new treatments. However, new technologies are available that can help solve these problems. The January 2023 NIPTE pathfinding workshop on accelerating drug product development and approval included a session in which participants considered the current state of product formulation and process development, barriers to acceleration of the development timeline, and opportunities for overcoming these barriers using new technologies. The authors participated in this workshop, and in this article have shared their perspective of some of the ways forward, including advanced manufacturing techniques and adaptive development. In addition, there is a need for paradigm shifts in regulatory processes, increased pre-competitive collaboration, and a shared strategy among regulators, industry, and academia.
Topics: Humans; Drug Approval; Drug Development; Drug Industry; Technology, Pharmaceutical; Pharmaceutical Preparations; Chemistry, Pharmaceutical; Drug Compounding
PubMed: 38698195
DOI: 10.1007/s11095-024-03708-z -
Journal of Racial and Ethnic Health... Aug 2023Pre-exposure prophylaxis (PrEP) provides a salient avenue to address the profound HIV-related health disparities that Black women in the United States face. This... (Review)
Review
OBJECTIVES
Pre-exposure prophylaxis (PrEP) provides a salient avenue to address the profound HIV-related health disparities that Black women in the United States face. This systematic review assessed the acceptability of PrEP within this population, and identified barriers and facilitators to its acceptability and uptake.
METHODS
We searched PubMed and Web of Science using 48 search input combinations; this produced 338 unique articles, 16 of which were included in the review.
RESULTS
We analyzed the results using the socio-ecological model (SEM). Findings indicate generally positive attitudes towards PrEP among Black women, although acceptance levels vary widely. Individual-level barriers included inadequate levels of PrEP awareness and knowledge, low HIV-risk perception, and concerns about adherence and side effects; interpersonal-level barriers were the influence of sexual and romantic partners and stigma from family; societal-level barriers included lack of PrEP marketing towards Black women, medical mistrust, cost, and structural violence. The main facilitators at the individual-level were PrEP education and information; at the interpersonal-level, distrust in sexual partners, healthcare provider encouragement, and social support; at the societal-level, PrEP accessibility, and affordability. No community-level barriers or facilitators were identified.
CONCLUSIONS
PrEP should be marketed directly to Black women in the US and campaigns should highlight this medication's effectiveness, accessibility, affordability, and safety. Medical mistrust must also be addressed to enable Black women to feel comfortable following their healthcare providers' advice regarding PrEP.
PubMed: 37531021
DOI: 10.1007/s40615-023-01729-9 -
Phytomedicine : International Journal... Jan 2024Drug-induced liver injury (DILI) is the most challenging and thought-provoking liver problem for hepatologists owing to unregulated medication usage in medical... (Review)
Review
BACKGROUND
Drug-induced liver injury (DILI) is the most challenging and thought-provoking liver problem for hepatologists owing to unregulated medication usage in medical practices, nutritional supplements, and botanicals. Due to underreporting, analysis, and identification issues, clinically evaluated medication hepatotoxicity is prevalent yet hard to quantify.
PURPOSE
This review's primary objective is to thoroughly compare pharmaceutical drugs and herbal compounds that have undergone clinical trials, focusing on their metabolic mechanisms contributing to the onset of liver illnesses and their hepatoprotective effects.
METHODS
The data was gathered from several online sources, such as PubMed, Scopus, Google Scholar, and Web of Science, using appropriate keywords.
RESULTS
The prevalence of conventional and herbal medicine is rising. A comprehensive understanding of the metabolic mechanism is necessary to mitigate the hepatotoxicity induced by drugs and facilitate the incorporation or substitution of herbal medicine instead of pharmaceuticals. Moreover, pre-clinical pharmacological research has the potential to facilitate the development of natural products as therapeutic agents, displaying promising possibilities for their eventual clinical implementation.
CONCLUSIONS
Acetaminophen, isoniazid, rifampicin, diclofenac, and pyrogallol have been identified as the most often reported synthetic drugs that produce hepatotoxicity by oxidative stress, inflammation, apoptosis, and fibrosis during the last several decades. Due to their ability to downregulate many factors (such as cytokines) and activate several enzyme/enzyme systems, herbal substances (such as Gingko biloba extract, curcumin, resveratrol, and silymarin) provide superior protection against harmful mechanisms which induce hepatotoxicity with fewer adverse effects than their synthetic counterparts.
Topics: Chemical and Drug Induced Liver Injury; Isoniazid; Plant Extracts; Plants, Medicinal; Silymarin; Liver
PubMed: 37913641
DOI: 10.1016/j.phymed.2023.155142 -
Molecular Therapy : the Journal of the... Aug 2023Cancer cachexia is a severe systemic wasting disease that negatively affects quality of life and survival in patients with cancer. To date, treating cancer cachexia is...
Cancer cachexia is a severe systemic wasting disease that negatively affects quality of life and survival in patients with cancer. To date, treating cancer cachexia is still a major unmet clinical need. We recently discovered the destabilization of the AMP-activated protein kinase (AMPK) complex in adipose tissue as a key event in cachexia-related adipose tissue dysfunction and developed an adeno-associated virus (AAV)-based approach to prevent AMPK degradation and prolong cachexia-free survival. Here, we show the development and optimization of a prototypic peptide, Pen-X-ACIP, where the AMPK-stabilizing peptide ACIP is fused to the cell-penetrating peptide moiety penetratin via a propargylic glycine linker to enable late-stage functionalization using click chemistry. Pen-X-ACIP was efficiently taken up by adipocytes, inhibited lipolysis, and restored AMPK signaling. Tissue uptake assays showed a favorable uptake profile into adipose tissue upon intraperitoneal injection. Systemic delivery of Pen-X-ACIP into tumor-bearing animals prevented the progression of cancer cachexia without affecting tumor growth and preserved body weight and adipose tissue mass with no discernable side effects in other peripheral organs, thereby achieving proof of concept. As Pen-X-ACIP also exerted its anti-lipolytic activity in human adipocytes, it now provides a promising platform for further (pre)clinical development toward a novel, first-in-class approach against cancer cachexia.
Topics: Animals; Humans; Adipose Tissue; AMP-Activated Protein Kinases; Cachexia; Neoplasms; Peptides; Pharmaceutical Preparations; Quality of Life
PubMed: 37408309
DOI: 10.1016/j.ymthe.2023.06.020 -
Military Medicine Jul 2023The recent article by Knisely et al. provides a comprehensive review and summary of recent literature describing simulation techniques, training strategies, and...
The recent article by Knisely et al. provides a comprehensive review and summary of recent literature describing simulation techniques, training strategies, and technologies to teach medics combat casualty care skills. Some of the results reported by Knisely et al. align with the findings of our team's work, and these findings may be helpful to military leadership with their ongoing efforts to maintain medical readiness. Accordingly, we provide some additional contextual understanding to the results of Knisely et al. in this commentary. Our team recently published two papers describing the results of a large survey that examined Army medic pre-deployment training. Combining the findings of Knisely et al. along with some of the contextual information from our work, we provide some recommendations for improving and optimizing the pre-deployment training paradigm for medics.
Topics: Humans; Military Medicine; Military Personnel; Clinical Competence; Simulation Training; Combat Medics
PubMed: 36848148
DOI: 10.1093/milmed/usad050 -
Current Heart Failure Reports Dec 2023Cardiac tissue regenerative strategies have gained much traction over the years, in particular those utilizing hydrogels. With our review, and with special focus on... (Review)
Review
PURPOSE OF REVIEW
Cardiac tissue regenerative strategies have gained much traction over the years, in particular those utilizing hydrogels. With our review, and with special focus on supporting post-myocardial infarcted tissue, we aim to provide insights in determining crucial design considerations of a hydrogel and the implications these could have for future clinical use.
RECENT FINDINGS
To date, two hydrogel delivery strategies are being explored, cardiac injection or patch, to treat myocardial infarction. Recent advances have demonstrated that the mechanism by which a hydrogel is gelated (i.e., physically or chemically cross-linked) not only impacts the biocompatibility, mechanical properties, and chemical structure, but also the route of delivery of the hydrogel and thus its effect on cardiac repair. With regard to cardiac regeneration, various hydrogels have been developed with the ability to function as a delivery system for therapeutic strategies (e.g., drug and stem cells treatments), as well as a scaffold to guide cardiac tissue regeneration following myocardial infarction. However, these developments remain within the experimental and pre-clinical realm and have yet to transition towards the clinical setting.
Topics: Humans; Hydrogels; Prospective Studies; Heart Failure; Myocardial Infarction; Myocardium
PubMed: 37812347
DOI: 10.1007/s11897-023-00630-0 -
Expert Opinion on Investigational Drugs 2023Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, in patients with liver disease, which affects life quality and span. Current treatments are lactulose or... (Review)
Review
INTRODUCTION
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, in patients with liver disease, which affects life quality and span. Current treatments are lactulose or rifaximin, acting on gut microbiota. Treatments aiming ammonia levels reduction have been tested with little success.
AREAS COVERED
Pre-clinical research shows that the process inducing HE involves sequentially: liver failure, altered microbiome, hyperammonemia, peripheral inflammation, changes in immunophenotype and extracellular vesicles and neuroinflammation, which alters neurotransmission impairing cognitive and motor function. HE may be reversed using drugs acting at any step: modulating microbiota with probiotics or fecal transplantation; reducing peripheral inflammation with anti-TNFα, autotaxin inhibitors or silymarin; reducing neuroinflammation with sulforaphane, p38 MAP kinase or phosphodiesteras 5 inhibitors, antagonists of sphingosine-1-phosphate receptor 2, enhancing meningeal lymphatic drainage or with extracellular vesicles from mesenchymal stem cells; reducing GABAergic neurotransmission with indomethacin or golexanolone.
EXPERT OPINION
A factor limiting the progress of HE treatment is the lack of translation of research advances into clinical trials. Only drugs acting on microbiota or ammonia reduction have been tested in patients. It is urgent to change the mentality on how to approach HE treatment to develop clinical trials to assess drugs acting on the immune system/peripheral inflammation, neuroinflammation or neurotransmission to improve HE.
Topics: Humans; Hepatic Encephalopathy; Drugs, Investigational; Neuroinflammatory Diseases; Ammonia; Inflammation
PubMed: 37902074
DOI: 10.1080/13543784.2023.2277386 -
Cancer Letters Jan 2024Small extracellular vesicles (sEVs) such as exosomes are nanoscale membranous particles (<200 nm) that have emerged as crucial targets for liquid biopsy and as... (Review)
Review
Small extracellular vesicles (sEVs) such as exosomes are nanoscale membranous particles (<200 nm) that have emerged as crucial targets for liquid biopsy and as promising drug delivery vehicles. They play a significant role in tumor progression as intercellular messengers. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment. This article reviews recent studies on sEVs in oncology and explores their potential as biomarkers and drug delivery vehicles. Following tumorigenesis, sEVs in the tumor microenvironment (TME) and circulatory system undergo modifications to regulate various events in the TME, including angiogenesis, epithelial-mesenchymal transition (EMT), and tumor immunity, with either pro- or anti-tumor effects. sEVs have been investigated for use as diagnostic and prognostic biomarkers for a variety of tumors, including lung cancer, melanoma, breast cancer, prostate cancer, and hepatocellular carcinoma. sEVs can be used for cancer therapy by packaging drugs or proteins into them through pre- and post-isolation modification techniques. The clinical trials of sEVs as biomarkers and drug carriers are also summarized. Finally, the challenges in the use of sEVs are described and the possible approaches to tackling them are suggested. Overall, sEVs will advance the precision cancer medicine and has shown great potential in clinical applications.
Topics: Male; Humans; Lung Neoplasms; Extracellular Vesicles; Drug Carriers; Liver Neoplasms; Biomarkers; Tumor Microenvironment
PubMed: 37972701
DOI: 10.1016/j.canlet.2023.216481 -
Advanced Drug Delivery Reviews Nov 2023Safe and efficient medical therapy for brain diseases is still an unmet clinical need due to various barriers represented by the blood-brain barrier. Well-designed brain... (Review)
Review
Safe and efficient medical therapy for brain diseases is still an unmet clinical need due to various barriers represented by the blood-brain barrier. Well-designed brain targeted nanocarriers are potential solutions for enhanced brain drug delivery; however, the complicated in vivo process attenuates performance of nanocarriers, which severely hampers clinical translation. The formation of protein corona (PC) is inevitable for nanocarriers circulation and transport in biofluids, acting as an important factor to regulate in vivo performance of nanocarriers. In this review, the reported strategies have been retrospected for better understanding current situation in developing brain targeted nanocarriers. The interplay between brain targeted nanocarriers and plasma proteins is emphasized to comprehend how the nanocarriers adsorb proteins by certain synthetic identity, and following regulations on in vivo performance of nanocarriers. More importantly, the mainstream methods to promote efficiency of nanocarriers by regulating PC, defined as in vitro functionalization and in vivo functionalization strategies, are also discussed. Finally, viewpoints about future development of brain targeted nanocarriers according to the understanding on nanocarriers-PC interaction are proposed.
Topics: Humans; Drug Carriers; Protein Corona; Nanoparticles; Drug Delivery Systems; Brain
PubMed: 37827336
DOI: 10.1016/j.addr.2023.115114