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Pharmaceutics Feb 2022Traumatic brain injuries (TBIs) are still a challenge for the field of modern medicine. Many treatment options such as autologous grafts and stem cells show limited...
Traumatic brain injuries (TBIs) are still a challenge for the field of modern medicine. Many treatment options such as autologous grafts and stem cells show limited promise for the treatment and the reversibility of damage caused by TBIs. Injury beyond the critical size necessitates the implementation of scaffolds that function as surrogate extracellular matrices. Two scaffolds were synthesised utilising polysaccharides, chitosan and hyaluronic acid in conjunction with gelatin. Both scaffolds were chemically crosslinked using a naturally derived crosslinker, Genipin. The polysaccharides increased the mechanical strength of each scaffold, while gelatin provided the bioactive sequence, which promoted cellular interactions. The effect of crosslinking was investigated, and the crosslinked hydrogels showed higher thermal decomposition temperatures, increased resistance to degradation, and pore sizes ranging from 72.789 ± 16.85 µm for the full interpenetrating polymer networks (IPNs) and 84.289 ± 7.658 μm for the semi-IPN. The scaffolds were loaded with Dexamethasone-21-phosphate to investigate their efficacy as a drug delivery vehicle, and the full IPN showed a 100% release in 10 days, while the semi-IPN showed a burst release in 6 h. Both scaffolds stimulated the proliferation of rat pheochromocytoma (PC12) and human glioblastoma multiforme (A172) cell cultures and also provided signals for A172 cell migration. Both scaffolds can be used as potential drug delivery vehicles and as artificial extracellular matrices for potential neural regeneration.
PubMed: 35214173
DOI: 10.3390/pharmaceutics14020441 -
Advanced Drug Delivery Reviews May 2013Nanoparticle-based drug delivery (NDD) has emerged as a promising approach to improving upon the efficacy of existing drugs and enabling the development of new... (Review)
Review
Nanoparticle-based drug delivery (NDD) has emerged as a promising approach to improving upon the efficacy of existing drugs and enabling the development of new therapies. Proof-of-concept studies have demonstrated the potential for NDD systems to simultaneously achieve reduced drug toxicity, improved bio-availability, increased circulation times, controlled drug release, and targeting. However, clinical translation of NDD vehicles with the goal of treating particularly challenging diseases, such as cancer, will require a thorough understanding of how nanoparticle properties influence their fate in biological systems, especially in vivo. Consequently, a model system for systematic evaluation of all stages of NDD with high sensitivity, high resolution, and low cost is highly desirable. In theory, this system should maintain the properties and behavior of the original NDD vehicle, while providing mechanisms for monitoring intracellular and systemic nanocarrier distribution, degradation, drug release, and clearance. For such a model system, quantum dots (QDots) offer great potential. QDots feature small size and versatile surface chemistry, allowing their incorporation within virtually any NDD vehicle with minimal effect on overall characteristics, and offer superb optical properties for real-time monitoring of NDD vehicle transport and drug release at both cellular and systemic levels. Though the direct use of QDots for drug delivery remains questionable due to their potential long-term toxicity, the QDot core can be easily replaced with other organic drug carriers or more biocompatible inorganic contrast agents (such as gold and magnetic nanoparticles) by their similar size and surface properties, facilitating translation of well characterized NDD vehicles to the clinic, maintaining NDD imaging capabilities, and potentially providing additional therapeutic functionalities such as photothermal therapy and magneto-transfection. In this review we outline unique features that make QDots an ideal platform for nanocarrier design and discuss how this model has been applied to study NDD vehicle behavior for diverse drug delivery applications.
Topics: Animals; Diagnostic Imaging; Drug Delivery Systems; Drug Design; Humans; Intracellular Fluid; Nanoparticles; Quantum Dots
PubMed: 23000745
DOI: 10.1016/j.addr.2012.09.036 -
Molecules (Basel, Switzerland) Jul 2020Antimicrobial peptides (AMPs), otherwise known as host defence peptides (HDPs), are naturally occurring biomolecules expressed by a large array of species across the... (Review)
Review
Antimicrobial peptides (AMPs), otherwise known as host defence peptides (HDPs), are naturally occurring biomolecules expressed by a large array of species across the phylogenetic kingdoms. They have great potential to combat microbial infections by directly killing or inhibiting bacterial activity and/or by modulating the immune response of the host. Due to their multimodal properties, broad spectrum activity, and minimal resistance generation, these peptides have emerged as a promising response to the rapidly concerning problem of multidrug resistance (MDR). However, their therapeutic efficacy is limited by a number of factors, including rapid degradation, systemic toxicity, and low bioavailability. As such, many strategies have been developed to mitigate these limitations, such as peptide modification and delivery vehicle conjugation/encapsulation. Oftentimes, however, particularly in the case of the latter, this can hinder the activity of the parent AMP. Here, we review current delivery strategies used for AMP formulation, focusing on methodologies utilized for targeted infection site release of AMPs. This specificity unites the improved biocompatibility of the delivery vehicle with the unhindered activity of the free AMP, providing a promising means to effectively translate AMP therapy into clinical practice.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Delivery Systems; Humans; Pore Forming Cytotoxic Proteins
PubMed: 32635310
DOI: 10.3390/molecules25133048 -
Pharmaceutics Mar 2019Prevention strategies play a key role in the fight against HIV/AIDS. Vaginal and rectal microbicides hold great promise in tackling sexual transmission of HIV-1, but... (Review)
Review
Prevention strategies play a key role in the fight against HIV/AIDS. Vaginal and rectal microbicides hold great promise in tackling sexual transmission of HIV-1, but effective and safe products are yet to be approved and made available to those in need. While most efforts have been placed in finding and testing suitable active drug candidates to be used in microbicide development, the last decade also saw considerable advances in the design of adequate carrier systems and formulations that could lead to products presenting enhanced performance in protecting from infection. One strategy demonstrating great potential encompasses the use of nanosystems, either with intrinsic antiviral activity or acting as carriers for promising microbicide drug candidates. Polymeric nanoparticles, in particular, have been shown to be able to enhance mucosal distribution and retention of promising antiretroviral compounds. One important aspect in the development of nanotechnology-based microbicides relates to the design of pharmaceutical vehicles that allow not only convenient vaginal and/or rectal administration, but also preserve or even enhance the performance of nanosystems. In this manuscript, we revise relevant work concerning the selection of vaginal/rectal dosage forms and vehicle formulation development for the administration of microbicide nanosystems. We also pinpoint major gaps in the field and provide pertinent hints for future work.
PubMed: 30917532
DOI: 10.3390/pharmaceutics11030145 -
Biochimica Et Biophysica Acta.... Jan 2017The nanoparticles referred as exosomes play an active role in intercellular communication. Their potential positive therapeutic effect in bacterial inflammation and... (Review)
Review
The nanoparticles referred as exosomes play an active role in intercellular communication. Their potential positive therapeutic effect in bacterial inflammation and sepsis has been the subject of several studies that have examined the feasibility of exosomes as drug-delivery vehicles. The underlying mechanism of interest involves the selective transport of cellular cargo. Most attention has been focused on the exosome-mediated transport of microRNA and protein. Thus, exosomes are expected to be an important tool in the treatment of inflammatory disease. This review covers the relevant literature, focusing on the relationship between exosomes and sepsis and therapeutic use of exosomes in bacterially mediated inflammation or sepsis. We evaluate exosomes as drug vehicles, including their therapeutic cargo, potential mechanisms of action, choice of donor cells, and routes of administration.
Topics: Animals; Cell Fractionation; Drug Carriers; Exosomes; Humans; Inflammation; MicroRNAs; Sepsis
PubMed: 27989958
DOI: 10.1016/j.bbadis.2016.10.024 -
Advanced Drug Delivery Reviews Jul 2023Topical eyedrop application is the preferred route for drug delivery to anterior segment tissues; however, the challenge of overcoming the eye's anatomical and... (Review)
Review
Topical eyedrop application is the preferred route for drug delivery to anterior segment tissues; however, the challenge of overcoming the eye's anatomical and physiological barriers while minimising tissue toxicity has restricted developments in this field. Aqueous vehicles have traditionally been used, which typically require several additives and preservatives to achieve physiologically compatible and sterile eyedrops, elevating their toxicity potential. Non-aqueous vehicles have been suggested as efficient alternatives for topical drug delivery as they can address many of the limitations associated with conventional aqueous eyedrops. However, despite their obvious advantages, non-aqueous eyedrops remain poorly researched and few non-aqueous formulations are currently available in the market. This review challenges the conventional hypothesis that aqueous solubility is a prerequisite to ocular drug absorption and establishes a rationale for using non-aqueous vehicles for ocular drug delivery. Recent advances in the field have been detailed and future research prospects have been explored, pointing towards a paradigm shift in eyedrop formulation in the near future.
Topics: Humans; Administration, Topical; Eye; Drug Delivery Systems; Ophthalmic Solutions
PubMed: 37178927
DOI: 10.1016/j.addr.2023.114867 -
The Journal of Pharmacology and... Aug 2019Mesenchymal stem cells (MSCs) have previously demonstrated considerable promise in regenerative medicine based on their ability to proliferate and differentiate into... (Review)
Review
Mesenchymal stem cells (MSCs) have previously demonstrated considerable promise in regenerative medicine based on their ability to proliferate and differentiate into cells of different lineages. More recently, there has been a significant interest in using MSCs as cellular vehicles for targeted cancer therapy by exploiting their tumor homing properties. Initial studies focused on using genetically modified MSCs for targeted delivery of various proapoptotic, antiangiogenic, and therapeutic proteins to a wide variety of tumors. However, their use as drug delivery vehicles has been limited by poor drug load capacity. This review discusses various strategies for the nongenetic modification of MSCs that allows their use in tumor-targeted delivery of small molecule chemotherapeutic agents. SIGNIFICANCE STATEMENT: There has been considerable interest in exploiting the tumor homing potential of MSCs to develop them as a vehicle for the targeted delivery of cytotoxic agents to tumor tissue. The inherent tumor-tropic and drug-resistant properties make MSCs ideal carriers for toxic payload. While significant progress has been made in the area of the genetic modification of MSCs, studies focused on identification of molecular mechanisms that contribute to the tumor tropism along with optimization of the engineering conditions can further improve their effectiveness as drug delivery vehicles.
Topics: Animals; Cell Engineering; Cell- and Tissue-Based Therapy; Humans; Mesenchymal Stem Cells; Neoplasms; Translational Research, Biomedical
PubMed: 31175219
DOI: 10.1124/jpet.119.259796 -
Frontiers in Chemistry 2018Targeted delivery of anticancer drugs is considered to be one of the pillars of cancer treatment as it could allow for a better treatment efficiency and less adverse... (Review)
Review
Targeted delivery of anticancer drugs is considered to be one of the pillars of cancer treatment as it could allow for a better treatment efficiency and less adverse effects. A promising drug delivery approach is magnetic drug targeting which can be realized if a drug delivery vehicle possesses a strong magnetic moment. Here, we discuss different types of magnetic nanomaterials which can be used as magnetic drug delivery vehicles, approaches to magnetic targeted delivery as well as promising strategies for the enhancement of the imaging-guided delivery and the therapeutic action.
PubMed: 30619827
DOI: 10.3389/fchem.2018.00619 -
Pediatric Nephrology (Berlin, Germany) Feb 2023Inherited kidney diseases (IKDs) are a large group of disorders affecting different nephron segments, many of which progress towards kidney failure due to the absence of... (Review)
Review
Inherited kidney diseases (IKDs) are a large group of disorders affecting different nephron segments, many of which progress towards kidney failure due to the absence of curative therapies. With the current advances in genetic testing, the understanding of the molecular basis and pathophysiology of these disorders is increasing and reveals new potential therapeutic targets. RNA has revolutionized the world of molecular therapy and RNA-based therapeutics have started to emerge in the kidney field. To apply these therapies for inherited kidney disorders, several aspects require attention. First, the mRNA must be combined with a delivery vehicle that protects the oligonucleotides from degradation in the blood stream. Several types of delivery vehicles have been investigated, including lipid-based, peptide-based, and polymer-based ones. Currently, lipid nanoparticles are the most frequently used formulation for systemic siRNA and mRNA delivery. Second, while the glomerulus and tubules can be reached by charge- and/or size-selectivity, delivery vehicles can also be equipped with antibodies, antibody fragments, targeting peptides, carbohydrates or small molecules to actively target receptors on the proximal tubule epithelial cells, podocytes, mesangial cells or the glomerular endothelium. Furthermore, local injection strategies can circumvent the sequestration of RNA formulations in the liver and physical triggers can also enhance kidney-specific uptake. In this review, we provide an overview of current and potential future RNA-based therapies and targeting strategies that are in development for kidney diseases, with particular interest in inherited kidney disorders.
Topics: Humans; Kidney; Kidney Glomerulus; Kidney Diseases; RNA, Small Interfering; RNA, Messenger
PubMed: 35507149
DOI: 10.1007/s00467-021-05352-w -
The Cochrane Database of Systematic... Apr 2009Workforce alcohol and drug testing is commonplace but its effect in reducing occupational injuries remains unclear. (Review)
Review
BACKGROUND
Workforce alcohol and drug testing is commonplace but its effect in reducing occupational injuries remains unclear.
OBJECTIVES
To assess the effects of alcohol and drug screening of occupational drivers (operating a motorised vehicle) in preventing injury or work-related effects such as sickness absence related to injury.
SEARCH STRATEGY
We searched the following databases up to June 2007 (or up to the latest issue then available): MEDLINE, EMBASE, The Cochrane Library, Cochrane Occupational Health Field's specialised register, DARE, PsychINFO, ERIC, ETOH, CISDOC, NIOSHTIC, TRANSPORT, Zetoc, Science Citation Index and Social Science Citation index and HSELINE. We also searched reference lists, relevant websites and conducted hand searching.
SELECTION CRITERIA
Randomised controlled trials (RCTs), cluster-randomised trials, controlled clinical trials, controlled before and after studies (more than three time points to be measured before and after the study) and interrupted time-series (ITS) studies that evaluated alcohol or drug screening interventions for occupational drivers (compared to another intervention or no intervention) with an outcome measured as a reduction in injury or a proxy measure thereof.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed study quality. We contacted authors of the included studies for further information.
MAIN RESULTS
We included two interrupted time-series studies conducted in the USA. One study was conducted in five large US transportation companies (N = 115,019) that carried passengers and/or cargo. Monthly injury rates were available from 1983 to 1999. In the study company, two interventions of interest were evaluated: mandatory random drug testing and mandatory random and for-cause alcohol testing programmes. The third study focused only on mandatory random drug testing and was conducted on federal injury data that covered all truck drivers of interstate carriers.We recalculated the results from raw data provided by the study authors. Following reanalysis, we found that in one study mandatory random and for-cause alcohol testing was associated with a significant decrease in the level of injuries immediately following the intervention (-1.25 injuries/100 person years, 95% CI -2.29 to -0.21) but did not significantly affect the existing long-term downward trend (-0.28 injuries/100 person years/year, 95% CI -0.78 to 0.21).Mandatory random drug testing was significantly associated with an immediate change in injury level following the intervention (1.26 injuries/100 person years, 95% CI 0.36 to 2.16) in one study, and in the second study there was no significant effect (-1.36/injuries/100 person years, 95% CI -1.69 to 0.41). In the long term, random drug testing was associated with a significant increase in the downward trend (-0.19 injuries/100 person years/year, 95% CI -0.30 to -0.07) in one study, the other study was also associated with a significant improvement in the long-term downward trend (-0.83 fatal accidents/100 million vehicle miles/year, 95% CI -1.08 to -0.58).
AUTHORS' CONCLUSIONS
There is insufficient evidence to advise for or against the use of drug and alcohol testing of occupational drivers for preventing injuries as a sole, effective, long-term solution in the context of workplace culture, peer interaction and other local factors. Cluster-randomised trials are needed to better address the effects of interventions for injury prevention in this occupational setting.
Topics: Accidents, Occupational; Alcoholism; Humans; Motor Vehicles; Substance Abuse Detection; Substance-Related Disorders; United States; Workplace; Wounds and Injuries
PubMed: 19370641
DOI: 10.1002/14651858.CD006566.pub2