-
Pharmaceuticals (Basel, Switzerland) Sep 2023Treating posterior segment and retinal diseases poses challenges due to the complex structures in the eye that act as robust barriers, limiting medication delivery and... (Review)
Review
Treating posterior segment and retinal diseases poses challenges due to the complex structures in the eye that act as robust barriers, limiting medication delivery and bioavailability. This necessitates frequent dosing, typically via eye drops or intravitreal injections, to manage diseases, often leading to side effects with long-term use. Suprachoroidal injection is a novel approach for targeted drug delivery to the posterior segment. The suprachoroidal space is the region between the sclera and the choroid and provides a potential route for minimally invasive medication delivery. Through a more targeted delivery to the posterior segment, this method offers advantages over other routes of administration, such as higher drug concentrations, increased bioavailability, and prolonged duration of action. Additionally, this approach minimizes the risk of corticosteroid-related adverse events such as cataracts and intraocular pressure elevation via compartmentalization. This review focuses on preclinical and clinical studies published between 2019 and 2023, highlighting the potential of suprachoroidal injection in treating a variety of posterior segment diseases. However, to fully harness its potential, more research is needed to address current challenges and limitations, such as the need for technological advancements, refinement of injection techniques, and consideration of cost and accessibility factors. Future studies exploring its use in conjunction with biotech products, gene therapies, and cell-based therapies can lead to personalized treatments that can revolutionize the field of ophthalmology.
PubMed: 37765048
DOI: 10.3390/ph16091241 -
The Journal of Allergy and Clinical... Mar 2024Systemic immunotherapeutics have been a clinical staple in the treatment of cancer, infectious diseases, organ and cell transplantation, autoimmunity, and allergies.... (Review)
Review
Systemic immunotherapeutics have been a clinical staple in the treatment of cancer, infectious diseases, organ and cell transplantation, autoimmunity, and allergies. Although their utility remains unquestioned, systemic administration of these drugs is associated with limited efficacy, significant adverse off-target effects, transient activity, and the requirement for frequent repeated dosing. To this end, recent technological advancements have provided novel means for sustained drug delivery to specific tissues and targeted localized approaches for immunotherapeutics. In this article, we present various cutting-edge platform technologies, including implants, multireservoir systems, and scaffolds encapsulating immunomodulatory agents for local administration. Examples of their application in cancer, cell transplantation, allergy, and infectious diseases are discussed, highlighting the potential of such systems for innovative immunomodulatory intervention.
Topics: Humans; Immunomodulation; Drug Delivery Systems; Neoplasms; Administration, Cutaneous; Communicable Diseases
PubMed: 38253261
DOI: 10.1016/j.jaci.2024.01.004 -
Advanced Science (Weinheim,... Feb 2024The complex anatomy and physiological barriers of the eye make delivering ocular therapeutics challenging. Generally, effective drug delivery to the eye is hindered by... (Review)
Review
The complex anatomy and physiological barriers of the eye make delivering ocular therapeutics challenging. Generally, effective drug delivery to the eye is hindered by rapid clearance and limited drug bioavailability. Biomaterial-based approaches have emerged to enhance drug delivery to ocular tissues and overcome existing limitations. In this review, some of the most promising long-acting injectables (LAIs) in ocular drug delivery are explored, focusing on novel design strategies to improve therapeutic outcomes. LAIs are designed to enable sustained therapeutic effects, thereby extending local drug residence time and facilitating controlled and targeted drug delivery. Moreover, LAIs can be engineered to enhance drug targeting and penetration across ocular physiological barriers.
Topics: Eye; Drug Delivery Systems; Injections; Ocular Physiological Phenomena; Biological Availability
PubMed: 38018313
DOI: 10.1002/advs.202306463 -
International Journal of Nanomedicine 2023Exosomes, as natural nanocarriers, characterized with low immunogenicity, non-cytotoxicity and targeted delivery capability, which have advantages over synthetic... (Review)
Review
Exosomes, as natural nanocarriers, characterized with low immunogenicity, non-cytotoxicity and targeted delivery capability, which have advantages over synthetic nanocarriers. Recently, exosomes have shown great potential as diagnostic markers for diseases and are also considered as a promising cell-free therapy. Engineered exosomes have significantly enhanced the efficacy and precision of delivering therapeutic agents, and are currently being extensively employed in targeted therapeutic investigations for various ailments, including oncology, inflammatory disorders, and degenerative conditions. Particularly, engineered exosomes enable therapeutic agent loading, targeted modification, evasion of MPS phagocytosis, intelligent control, and bioimaging, and have been developed as multifunctional nano-delivery platforms in recent years. The utilization of bioactive scaffolds that are loaded with exosome delivery has been shown to substantially augment retention, extend exosome release, and enhance efficacy. This approach has advanced from conventional hydrogels to nanocomposite hydrogels, nanofiber hydrogels, and 3D printing, resulting in superior physical and biological properties that effectively address the limitations of natural scaffolds. Additionally, plant-derived exosomes, which can participate in gut flora remodeling via oral administration, are considered as an ideal delivery platform for the treatment of intestinal diseases. Consequently, there is great interest in exosomes and exosomes as nanocarriers for therapeutic and diagnostic applications. This comprehensive review provides an overview of the biogenesis, composition, and isolation methods of exosomes. Additionally, it examines the pathological and diagnostic mechanisms of exosomes in various diseases, including tumors, degenerative disorders, and inflammatory conditions. Furthermore, this review highlights the significance of gut microbial-derived exosomes. Strategies and specific applications of engineered exosomes and bioactive scaffold-loaded exosome delivery are further summarized, especially some new techniques such as large-scale loading technique, macromolecular loading technique, development of multifunctional nano-delivery platforms and nano-scaffold-loaded exosome delivery. The potential benefits of using plant-derived exosomes for the treatment of gut-related diseases are also discussed. Additionally, the challenges, opportunities, and prospects of exosome-based nanocarriers for disease diagnosis and treatment are summarized from both preclinical and clinical viewpoints.
Topics: Exosomes; Administration, Oral; Cell- and Tissue-Based Therapy; Gastrointestinal Microbiome; Hydrogels
PubMed: 37635911
DOI: 10.2147/IJN.S417422 -
PloS One 2023Riluzole is the only treatment known to improve survival in patients with Amyotrophic Lateral Sclerosis (ALS). However, oral riluzole efficacy is modest at best, further...
Riluzole is the only treatment known to improve survival in patients with Amyotrophic Lateral Sclerosis (ALS). However, oral riluzole efficacy is modest at best, further it is known to have large inter-individual variability of serum concentration and clearance, is formulated as an oral drug in a patient population plagued with dysphagia, and has known systemic side-effects like asthenia (limiting patient compliance) and elevated liver enzymes. In this context, we postulated that continuous intrathecal (IT) infusion of low doses of riluzole could provide consistent elevations of the drug spinal cord (SC) concentrations at or above those achieved with oral dosing, without increasing the risk for adverse events associated with systemic drug exposure or off-target side effects in the brain. We developed a formulation of riluzole for IT delivery and conducted our studies in purpose-bred hound dogs. Our non-GLP studies revealed that IT infusion alone was able to increase SC concentrations above those provided by oral administration, without increasing plasma concentrations. We then conducted two GLP studies that combined IT infusion with oral administration at human equivalent dose, to evaluate SC and brain concentrations of riluzole along with assessments of safety and tolerability. In the 6-week study, the highest IT dose (0.2 mg/hr) was well tolerated by the animals and increased SC concentrations above those achieved with oral riluzole alone, without increasing brain concentrations. In the 6-month study, the highest dose tested (0.4 mg/hr) was not tolerated and yielded SC significantly above those achieved in all previous studies. Our data show the feasibility and safety profile of continuous IT riluzole delivery to the spinal cord, without concurrent elevated liver enzymes, and minimal brain concentrations creating another potential therapeutic route of delivery to be used in isolation or in combination with other therapeutics."
Topics: Humans; Animals; Dogs; Amyotrophic Lateral Sclerosis; Riluzole; Brain; Administration, Oral; Drug-Related Side Effects and Adverse Reactions
PubMed: 37607205
DOI: 10.1371/journal.pone.0277718 -
Expert Opinion on Drug Delivery 2023Rapid advances in bioengineering enable the use of complex proteins as therapeutic agents to treat diseases. Compared with conventional small molecule drugs, proteins... (Review)
Review
INTRODUCTION
Rapid advances in bioengineering enable the use of complex proteins as therapeutic agents to treat diseases. Compared with conventional small molecule drugs, proteins have multiple advantages, including high bioactivity and specificity with low toxicity. Developing oral dosage forms with active proteins is a route to improve patient compliance and significantly reduce production costs. However, the gastrointestinal environment remains a challenge to this delivery path due to enzymatic degradation, low permeability, and weak absorption, leading to reduced delivery efficiency and poor clinical outcomes.
AREAS COVERED
This review describes the barriers to oral delivery of peptides and complex proteins, current oral delivery strategies utilized and the opportunities and challenges ahead to try and circumvent these barriers. Oral protein drugs on the market and clinical trials provide insights and approaches for advancing delivery strategies.
EXPERT OPINION
Although most current studies on oral protein delivery rely on and animal data, the safety and limitations of the approach in humans remain uncertain. The shortage of clinical data limits the development of new or alternative strategies. Therefore, designing appropriate oral delivery strategies remains a significant challenge and requires new ideas, innovative design strategies and novel model systems.
Topics: Animals; Humans; Drug Delivery Systems; Administration, Oral; Proteins; Peptides
PubMed: 37450427
DOI: 10.1080/17425247.2023.2237408 -
Journal of Controlled Release :... Aug 2023Microneedles (MNs) are micron-sized protrusions attached to a range of devices that are used in therapeutic delivery and diagnosis. Because MNs can be self-applied, are... (Review)
Review
Microneedles (MNs) are micron-sized protrusions attached to a range of devices that are used in therapeutic delivery and diagnosis. Because MNs can be self-applied, are painless, and can carry multiple therapeutic agents, they have received extensive attention, and have been widely investigated, for local and systemic therapy. Many researchers are currently working to extend the use of MNs to clinical applications. In this review, we provide an update and analysis on MN-based clinical trials since their inception in 2007. The MNs in clinical trials are classified into five types based on their appearance and properties, including: hollow MNs, MN patches, radiofrequency MNs, MN rollers, and other MNs. The various aspects of MN trials are summarized, such as MN types, clinical trial time, and trial regions. This review aims to present an overview of MN development and provide insights for future research in this field. To our knowledge, this is the first review focused on MN clinical trials which showcases the latest applications of this advanced technology in medicine.
Topics: Skin; Administration, Cutaneous; Drug Delivery Systems; Microinjections; Needles
PubMed: 37442203
DOI: 10.1016/j.jconrel.2023.07.023 -
Farmacia Hospitalaria : Organo Oficial... May 2024To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and... (Review)
Review
PURPOSE
To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety.
METHODS
Systematic review on the databases PubMed, ISI Web of Science, SCOPUS and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1,040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included.
RESULTS
NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischemia and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA.
CONCLUSIONS
Peripheral infusions of NA could be a safe and beneficial option in early resuscitation provided that a number of guidelines are followed that reduce the likelihood of complications associated with this route.
PubMed: 38724402
DOI: 10.1016/j.farma.2024.04.003 -
International Journal of Molecular... Oct 2023The landscape of ophthalmology is undergoing significant transformations, driven by technological advancements and innovations in materials science. One of the... (Review)
Review
The landscape of ophthalmology is undergoing significant transformations, driven by technological advancements and innovations in materials science. One of the advancements in this evolution is the application of nanoporous materials, endowed with unique physicochemical properties ideal for a variety of ophthalmological applications. Characterized by their high surface area, tunable porosity, and functional versatility, these materials have the potential to improve drug delivery systems and ocular devices. This review, anchored by a comprehensive literature focusing on studies published within the last five years, examines the applications of nanoporous materials in ocular drug delivery systems (DDS), contact lenses, and intraocular lenses. By consolidating the most current research, this review aims to serve as a resource for clinicians, researchers, and material scientists engaged in the rapidly evolving field of ophthalmology.
Topics: Nanopores; Drug Delivery Systems; Eye; Administration, Ophthalmic; Contact Lenses
PubMed: 37958583
DOI: 10.3390/ijms242115599 -
The Journal of Maternal-fetal &... Dec 2024This study aims to compare the safety and efficacy of misoprostol administered orally and vaginally in obese pregnant women at term with either gestational hypertension...
OBJECTIVE
This study aims to compare the safety and efficacy of misoprostol administered orally and vaginally in obese pregnant women at term with either gestational hypertension or diabetes.
METHODS
A total of 264 pregnant women were enrolled and categorized into two groups based on their primary condition: hypertension (134 cases) or diabetes mellitus (130 cases) and were further divided into subgroups for misoprostol administration: orally (Oral group) or vaginally (Vaginal group). The primary outcomes measured were changes in the Bishop score following treatment, induction of labor (IOL) success rates, requirement for oxytocin augmentation, duration of labor, mode of delivery, and cesarean section rates.
RESULTS
Significant enhancements in Bishop scores, decreased cesarean section rates and increased success rates of IOL were noted in both administration groups. The incidence of vaginal delivery within 24 h was significantly higher in the Vaginal group compared to the Oral group. Adverse effects, including nausea, uterine overcontraction, hyperfrequency of uterine contraction and uterine hyperstimulation without fetal heart rate deceleration, were significantly more prevalent in the Vaginal group than in the Oral group.
CONCLUSION
Misoprostol administration, both orally and vaginally, proves effective for labor induction in obese pregnant women with hypertension or diabetes. However, the oral route presents a lower risk of adverse maternal and neonatal outcomes, suggesting its preference for safer labor induction in this demographic.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Misoprostol; Oxytocics; Pregnant Women; Administration, Intravaginal; Cesarean Section; Labor, Induced; Administration, Oral; Hypertension, Pregnancy-Induced; Diabetes Mellitus
PubMed: 38485520
DOI: 10.1080/14767058.2024.2327573