Expert opinion on drug delivery最新文献

Introduction: Targeted liposomal systems for cancer intention have been recognized as a specific and robust approach compared to conventional liposomal delivery systems. Cancer cells have a unique microenvironment with special over-expressed receptors on their surface, providing opportunities for discovering novel and effective drug delivery systems using active targeting.

Areas covered: Smartly targeted liposomes, responsive to internal or external stimulations, enhance the delivery efficiency by increasing accumulation of the encapsulated anti-cancer agent in the tumor site. The application of antibodies and aptamers against the prevalent cell surface receptors is a potent and ever-growing field. Moreover, immuno-liposomes and cancer vaccines as adjuvant chemotherapy are also amenable to favorable immune modulation. Combinational and multi-functional systems are also attractive in this regard. However, potentially active targeted liposomal drug delivery systems have a long path to clinical acceptance, chiefly due to cross-interference and biocompatibility affairs of the functionalized moieties.

Expert opinion: Engineered liposomal formulations have to be designed based on tissue properties, including surface chemistry, charge, and microvasculature. In this paper, we aimed to investigate the updated targeted liposomal systems for common cancer therapy worldwide.

Introduction: High incidence and fatality rates of cancer remain a global challenge. The success of conventional treatment modalities is being questioned on account of adverse effects. Photodynamic therapy (PDT) is a potential alternative. It utilizes a combination of photosensitizer (PS), light and oxygen to target the tissues locally, thereby minimizing the damage to neighboring healthy tissues. Conventional PSs suffer from poor selectivity, high hydrophobicity and sub-optimal yield of active radicals. Graphene nanomaterials (GNs) exhibit interesting particulate and photophysical properties in the context of their use in PDT.

Area covered: We focus on describing the mechanistic aspects of PDT-mediated elimination of cancer cells and the subsequent development of adaptive immunity. After covering up-to-date literature on the significant enhancement of PDT capability with GNs, we have discussed the probability of combining PDT with chemo-, immuno-, and photothermal therapy to make the treatment more effective.

Expert opinion: GNs can be synthesized in various size ranges, and their biocompatibility can be improved through surface functionalization and doping. These can be used as PS to generate ROS or conjugated with other PS molecules for treating deep-seated tumors. With increasing evidence on biosafety, such materials offer hope as antitumor therapeutics.

Introduction: In recent years, chimeric antigen receptor T (CAR-T) cell therapy has resulted in a breakthrough in the treatment of patients with refractory or relapsed hematological malignancies. However, the identification of patients suitable for CAR-T cell therapy needs to be improved.

Areascovered: CAR-T cell therapy has demonstrated excellent efficacy in hematological malignancies; however, views on determining when to apply CAR-T cells in terms of the evaluation of patient characteristics remain controversial.

Expert opinion: We reviewed the current feasibility and challenges of CAR-T cell therapy in the most common hematological malignancies and classified them according to disease type and treatment priority, to guide clinicians and researchers in applying and investigating CAR-T cells further.

Introduction: Transdermal drug delivery (TDD) is becoming more recognized as a noninvasive method particularly suitable for vulnerable populations. TDD offers an alternative to oral drug delivery, bypassing issues related to poor absorption and metabolism. However, the application of TDD is limited to a few drugs due to the skin's barrier. Various techniques, including passive methods like nanoparticles (NPs), are being explored to enhance drug permeability through the skin.

Areas covered: This review shows the benefit of incorporating inorganic NPs with TDD in improving drug delivery through the skin. Despite the potential of these techniques, there are currently only a few research studies that utilize them. This review addresses the scarcity of research incorporating inorganic NPs with TDD. It also aims to summarize both inorganic NPs and TDD in the pharmaceutical industry, highlighting the advantages of incorporating these novel drug delivery systems with each other.

Expert opinion: Given the potential benefits of incorporating inorganic NPs into TDD systems, there is a need for increased research and attention in this area. The review encourages scientists to address the existing research gap and explore the advantages of combining these innovative drug delivery systems to advance the field.

Introduction: Skin carcinoma, including malignant melanoma, basal, squamous, and Merkel cell carcinoma, present significant healthcare challenges. Conventional treatments like surgery and chemotherapy suffer from limitations like non-specificity, toxicity, and adverse effects. The upcoming treatments are dominated by nano-sized delivery systems, which improve treatment outcomes while minimizing side effects. Moving ahead, targeted nanoparticles allow localized delivery of drugs at tumor site, ensuring minimal damage to surrounding tissues.

Areas covered: This review explores various targeting strategies for specific types of skin cancers. The strategies discussed include nanocarrier-mediated targeted delivery with multiple types of ligands like aptamers, antibodies, peptides, and vitamins and their advantages in skin cancer. Upcoming cutting-edge technologies such as smart delivery systems, microneedle-assisted delivery and three-dimensional printed scaffolds have also been discussed in detail. The findings in this review are summarized from databases like PubMed, Scopus, Web of Science, ClinicalTrials.gov, NIH, and articles published between 2005 and 2024 that discuss targeted therapy for skin cancer.

Expert opinion: Specific cancer-targeting strategies promise personalized treatments, improving response rates and reducing need for intensive therapies. The review highlights various challenges, their solution, and economic aspects in this dynamic field. It further emphasizes the potential for specialized strategies to revolutionize skin cancer treatment.

Background: The administration of repository corticotropin injection (Acthar Gel) via a single-dose prefilled injector (SelfJect) is intended to provide a simple, ergonomic alternative to traditional injection. Iterative human factors (HF) studies were conducted to identify potential use deviations and ensure appropriate device use.

Research design and methods: This article presents seven formative studies, a validation study (with prior pilot validation studies), and a supplemental validation study with participants including lay users, patients, caregivers, and healthcare providers. Participant interactions with SelfJect and the user interface were assessed. Use deviations, user preferences, and participants' ability to successfully complete tasks were evaluated to generate modifications to the device and user interface.

Results: In the validation study, 91% of participants successfully administered their first injection. Use errors were rare with simulated-use (6.9%) and knowledge-based (1.6%) testing. Use deviations were commonly attributed to experimental artifact or information oversight, and device warming had the most use errors (49% of participants), even with extensive testing and adjustments to the user interface.

Conclusions: SelfJect was able to be used in a safe and effective manner by the intended users. Iterative HF studies informed the mitigation of use-related risks to reduce the occurrence of use deviations during simulated use.

Background: Oral delivery of small interfering RNAs (siRNAs) draws significant attention, but the gastrointestinal tract (GIT) has many biological barriers that limit the drugs' bioavailability. The aim of this work was to investigate the potential of micro- and nano-sized CaCO₃ and PLA carriers for oral delivery of siRNA and reveal a relationship between the physicochemical features of these carriers and their biodistribution.

Research design and methods: In vitro stability of carriers was investigated in simulated gastric and intestinal fluids. Toxicity and cellular uptake were investigated on Caco-2 cells. The biodistribution profiles of the developed CaCO₃ and PLA carriers were examined using different visualization methods, including SPECT, fluorescence imaging, radiometry, and histological analysis. The delivery efficiency of siRNA loaded carriers was investigated both in vitro and in vivo.

Results: Micro-sized carriers were accumulated in the stomach and later localized in the colon tissues. The nanoscale particles (100-250 nm) were distributed in the colon tissues. nPLA was also detected in small intestine. The developed carriers can prevent siRNA from premature degradation in GIT media.

Conclusion: Our results reveal how the physicochemical properties of the particles, including their size and material type can affect their biodistribution profile and oral delivery of siRNA.

Introduction: Intramuscular (IM) injections deliver a plethora of drugs. The majority of IM-related literature details dissolution and/or pharmacokinetic (PK) studies, using methods with limited assessments of post-injection events that can impact drug fate, and absorption parameters. Food and Drug Association guidelines no longer require preclinical in vivo modeling in the U.S.A. Preclinical animal models fail to correlate with clinical outcomes, highlighting the need to study, and understand, IM drug fate in vitro using bespoke models emulating human IM sites. Post-IM injection events, i.e. underlying processes that influence PK outcomes, remain unacknowledged, complicating the application of in vitro methods in preclinical drug development. Understanding such events could guide approaches to predict and modulate IM drug fate in humans.

Areas covered: This article reviews challenges in biorelevant IM site modeling (i.e. modeling drug fate outcomes), the value of technologies available for developing IM injectables, methods for studying drug fate, and technologies for training in performing IM administrations. PubMed, Web-of-Science, and Lens databases provided papers published between 2014 and 2024.

Expert opinion: IM drug research is expanding what injectable therapeutics can achieve. However, post-injection events that influence PK outcomes remain poorly understood. Until addressed, advances in IM drug development will not realize their full potential.

Introduction: The deposition of inhaled medications is the first step in the pulmonary pharmacokinetic process to produce a therapeutic response. Not only lung dose but more importantly the distribution of deposited drug in the different regions of the lung determines local bioavailability, efficacy, and clinical safety. Assessing aerosol deposition patterns has been the focus of intense research that combines the fields of physics, radiology, physiology, and biology.

Areas covered: The review covers the physics of aerosol transport in the lung, experimental, and in-silico modeling approaches to determine lung dose and aerosol deposition patterns, the effect of asthma, chronic obstructive pulmonary disease, and cystic fibrosis on aerosol deposition, and the clinical translation potential of determining aerosol deposition dose.

Expert opinion: Recent advances in in-silico modeling and lung imaging have enabled the development of realistic subject-specific aerosol deposition models, albeit mainly in health. Accurate modeling of lung disease still requires additional refinements in existing imaging and modeling approaches to better characterize disease heterogeneity in peripheral airways. Nevertheless, recent patient-centric innovation in inhaler device engineering and the incorporation of digital technology have led to more consistent lung deposition and improved targeting of the distal airways, which better serve the clinical needs of patients.

Introduction: Development of novel vascular networks is a fundamental requirement for tumor growth and progression. In the last decade, biomarkers and underlying molecular pathways of angiogenesis have been intensely investigated to disrupt the initiation and progression of tumor angiogenesis. However, the clinical applications of anti-angiogenic agents are constrained due to toxic side effects, acquired drug resistance, and unavailability of validated biomarkers.

Area covered: This review discusses the development of dendrimeric nanocarriers that could be a promising domain to explore for the eradication of current challenges associated with angiogenesis-based cancer therapy. Novel drug-delivery approaches with subtle readouts and better understanding of molecular mechanisms have revealed that dendrimers comprise innate anti-angiogenic activity and incorporation of anti-angiogenic agents or gene-silencing RNA could lead to synergistic anti-angiogenic and anticancer effects with reduced side effects.

Expert opinion: Dendrimer-mediated targeting of angiogenic biomarkers has efficiently led to the vascular normalization, and rational linking of dendrimers with anti-angiogenic agent or siRNA or both might be a potential area to eradicate the current challenges of angiogenesis-based cancer therapy. However, drawbacks associated with the dendrimers-mediated targeting of angiogenic biomarkers, such as poor stability or small expression of these biomarkers on the normal cells, limit their application at market scale.