Expert opinion on drug delivery最新文献

Introduction: Viral vectors have proven useful for delivering genetic information, such as drugs and vaccines, for therapeutic and prophylactic interventions. Self-amplifying RNA viruses possess the special feature of high-level RNA amplification in the host cell cytoplasm providing high antigen production against infectious pathogens and various types of cancers, and expression of anti-tumor genes, toxic genes, and immunostimulatory genes.

Areas covered: Self-amplifying RNA viral vectors have been evaluated in animal models and clinical trials for immune responses and protection against challenges with pathogenic infectious agents and tumor cells. Likewise, immune responses, tumor regression, and tumor eradication have been monitored in preclinical and clinical settings. The literature search used in the review is based on PubMed and clinical trial/biotechnology company websites up until September 2024.

Expert opinion: Self-amplifying RNA viruses have elicited strong immune responses and vaccine efficacy in animal models and humans leading to the approval of the vesicular stomatitis virus-based vaccine against Ebola virus disease in both the US and Europe. Moreover, therapeutic and prophylactic efficacy has been demonstrated in animal tumor models and cancer patients. Self-amplifying RNA viruses have also been evaluated in mouse models for neurological disorders.

Introduction: The pursuit of linear dosage in pharmacy is essential for achieving consistent therapeutic release and enhancing patient compliance. This review provides a comprehensive summary of zero-order drug delivery systems, with a particular focus on reservoir-based systems emanated from different microfabrication technologies.

Areas covered: The consideration of recent advances in drug delivery systems is given to encompass the key areas including the importance of achieving a constant drug release rate for therapeutic applications. Detailed examination of reservoir-based systems, their design, mechanisms of action and materials used are highlighted. By addressing these areas, the discussion aims to provide a thorough understanding of most recent zero-order drug delivery systems, their performance advantages and methods of their manufacturing. To ensure the complete coverage of the explored research area, modern AI-assistant tools were used to find not only the most relevant, but also connected and similar articles.

Expert opinion: Future developments in reservoir-based drug delivery systems are expected to significantly enhance therapeutic effectiveness and patient outcomes through the integration of innovative materials and technologies. The fabrication of intelligent drug delivery systems that utilize sensors and feedback mechanisms can enable real-time monitoring of drug release and patient reactions.

Introduction: Hypoxia-inducible factor 1α [HIF1α] regulates gene expression, allowing the organism to respond to low oxygen levels. Meanwhile, astrocytes participate in inflammatory processes and are associated with neurotoxic chemicals that can increase stroke volume, contributing considerably to the devastating effects of a stroke.

Objective: To evaluate whether Hif-1α ablation from the central nervous system is implicated in motor dysfunction and ischemic brain damage following stroke. Furthermore, to explore if Hif-1α ablation affects the therapeutic impact of NeuroD1 gene-based therapy.

Methods: Endothelin-1 [ET-1] was injected to induce ischemic stroke in mice. Both wild-type and Hypoxia-inducible factor 1α conditional knockout [Hif-1α CKO] mice were used. The effect of Hif-1α ablation was assessed by the neuron numbers, astrocyte activity, vascular endothelial growth factor [VEGF] expression, and behavioral tests. Moreover, western blot, ELISA, and RNA sequencing were used. Then, we used pAAV2/9-GfaABC1D-NeuroD1-P2A-EGFP-WPRE injection to examine the impact of NeuroD1 in Hif-1α CKO mice following ischemic stroke.

Results: We found that following stroke, motor dysfunction significantly increased in Hif-1α CKO mice. Furthermore, elevation of apoptosis and activation in both microglia and astrocytes were observed, consequently up-regulating neuroinflammation. Meanwhile, Hif-1α ablation significantly decreased the efficiency of NeuroD1 gene-based therapy.

Conclusion: Our findings demonstrate that Hif-1α ablation from the nervous system is implicated in ischemic stroke pathogenesis mainly by increasing neuron cell death and inducing astrocytes as well as decreasing the efficiency of NeuroD1. These data support the idea that manipulating HIF-1α is a viable therapeutic for ischemic stroke.

Introduction: The blood-brain barrier (BBB) is a highly selective structure that protects the central nervous system (CNS) while hindering the delivery of many therapeutic agents. This presents a major challenge in treating neurological disorders, such as multiple sclerosis, where effective drug delivery to the brain is crucial for improving patient outcomes. Innovative strategies are urgently needed to address this limitation.

Areas covered: This review explores the potential of extracellular vesicles (EVs) as innovative drug delivery systems capable of crossing the BBB. EVs are membrane-bound vesicles derived from cells, tissues, or plant materials, offering natural biocompatibility and therapeutic potential. Recent studies investigating the permeability of EVs and their mechanisms for crossing the BBB, such as transcytosis, are summarized. Special emphasis is placed on plant-derived EVs (PDEVs) due to their unique advantages in drug delivery. Challenges related to the large-scale production and therapeutic consistency of EVs are also discussed.

Expert opinion: EVs, particularly PDEVs, hold significant promise as scalable and noninvasive systems for CNS drug delivery. However, critical barriers such as improving standardization techniques, manufacturing processes and addressing scalability must be overcome to facilitate clinical translation. Collaborative efforts in research and innovation will be pivotal in realizing the therapeutic potential of EVs for neurological conditions.

Introduction: Emulgel is a novel formulation that improves drug's stability and topical administration by combining emulsion and gel matrix. Its special structure improves skin penetration and prolongs the release of therapeutic molecules. Emulgel is unique in the commercial market because of its therapeutic effects, convenience of usage, and versatility in both pharmaceutical and cosmetic uses. This report focuses on how it may improve user experience and transform topical treatments.

Areas covered: This review explores the commercial applicability of emulgels as a topical delivery system. Industrially applicable composition and manufacturing strategies have been discussed along with characterization techniques. The market landscape, being the most critical aspect, has been thoroughly discussed with recent case studies, clinical trials, patents, and commercial formulations. The compiled findings in this review are adapted from reputed databases like Scopus, PubMed, Web of Science, NIH, ClinicalTrials.gov, Espacenet, and recent research articles published between years 2010-2024 that discussed the applications of emulgel.

Expert opinion: Emulgels have gained commercialization potential because of their efficient drug delivery and patient-friendly qualities. However, navigating regulatory complexity is important because imprecise classifications may affect market access. Sustained innovation will be essential for overcoming these obstacles and improving chances in future.

Background: The identification of drugs targeting multiple pathways is essential for comprehensive protection against cerebral ischemia-reperfusion injury.

Research design and methods: This study aimed to develop RS31, a multi-target cytoprotectant composed of SS31 (an oxidative stress mitigator) and rapamycin (Rapa), contributes anti-inflammatory and blood-brain barrier protection. RS31 was synthesized using click chemistry, and its ability to scavenge reactive oxygen species (ROS) and reduce inflammation was tested in H₂O₂-injured PC12 cells and LPS-stimulated BV2 cells. A C57BL/6 mouse model of transient middle cerebral artery occlusion/reperfusion (tMCAO/R) was established to assess the effect of RS31 on inflammatory factors in ischemic brain tissue. Finally, the potential of combining RS31 with PLGA microparticles (MPs) to further reduce brain edema was investigated.

Results: RS31 effectively scavenged ROS and reduced inflammation. It showed a ~ 4-fold higher concentration in cerebral ischemic regions, significant reducing infarction and improving neurological function. RS31 also effectively reduced inflammatory factors, lowered malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD) activity, showing strong efficacy in treating ischemic stroke.

Conclusions: In vivo delivery of RS31 is an effective therapeutic strategy for I/R injury, providing a general framework for developing multi-targeted drugs against inflammatory diseases and excessive ROS production.

Introduction: Clinical outcomes for the treatment of peritoneal carcinomatosis (PC) have remained suboptimal. Microsphere-based intraperitoneal chemotherapy has shown considerable potential in preclinical studies. However, due to the complications associated with peritoneal adhesions, there has been a lack of comprehensive reviews focusing on the progress of microsphere applications in the treatment of PC.

Areas covered: We provide an overview of the current clinical treatment strategies for PC and analyze the potential advantages of microspheres in this context. Regarding the issue of peritoneal adhesions induced by microspheres, we investigate the underlying mechanisms and propose possible solutions. Furthermore, we outline the future directions for the development of microsphere-based therapies in the treatment of PC.

Expert opinion: Microspheres formulated with highly biocompatible materials to the peritoneum, such as sodium alginate, gelatin, or genipin, or with an optimal particle size (4 ~ 30 μm) and lower molecular weights (10 ~ 57 kDa), can prevent peritoneal adhesions and improve drug distribution. To further enhance the antitumor efficacy, enhancing the tumor penetration capability and specificity of microspheres, optimizing intraperitoneal distribution, and addressing tumor resistance have demonstrated significant potential in preclinical studies, offering new therapeutic prospects for the treatment of PC.

Introduction: For three decades since the term 'biomaterial' was defined in the late 1960s, the interest of the biomaterials research community in calcium phosphates (CaPs) constantly increased. After this interest reached its peak in the mid-1990s, however, it has begun its steady decline, which lasts to this day, the reasons being manifold, many of which are explicated in this review piece. As of this turning point onwards, one solution for CaP to regain its relevance has involved its use in composite structures where properties of complementary components are intended to mitigate each other's weaknesses. A major type of such hybrid particulate structures has included CaP as a surface coating, the goal being to augment bioactivity, promote an intimate interaction with living tissues, facilitate cellular uptake and/or impart smart, pH-sensitive properties to the particles, among other intended effects.

Areas covered: In this review article, historical remarks, recent examples, challenges and opportunities pertaining to CaP-coated nanoparticles for drug delivery are elaborated. Discussion is supplemented with a bibliographic analysis and framed within a chronological timeline.

Expert opinion: Phenomenal properties and functions are bound to be elicited by composite structures containing CaP coatings and it is imperative that the exploration of these hybrids continues in decades that follow.