Expert opinion on drug delivery最新文献

Introduction: Three-Dimensional (3D) microneedles have recently gained significant attention due to their versatility, biocompatibility, enhanced permeation, and predictable behavior. The incorporation of biological agents into these 3D constructs has advanced the traditional microneedle into an effective platform for wide-ranging applications.

Areas covered: This review discusses the current state of microneedle fabrication as well as the developed 3D printed microneedles incorporating labile pharmaceutical agents and biological materials for potential biomedical applications. The mechanical and processing considerations for the preparation of microneedles and the barriers to effective 3D printing of microneedle constructs have additionally been reviewed along with their therapeutic applications and potential for tissue engineering and regenerative applications. Additionally, the regulatory considerations for microneedle approval have been discussed as well as the current clinical trial and patent landscapes.

Expert opinion: The fields of tissue engineering and regenerative medicine are evolving at a significant pace with researchers constantly focused on incorporating advanced manufacturing techniques for the development of versatile, complex, and biologically specific platforms. 3D bioprinted microneedles, fabricated using conventional 3D printing techniques, have resultantly provided an alternative to 2D bioscaffolds through the incorporation of biological materials within 3D constructs while providing further mechanical stability, increased bioactive permeation and improved innervation into surrounding tissues. This advancement therefore potentially allows for a more effective biomimetic construct with improved tissue-specific cellular growth for the enhanced treatment of physiological conditions requiring tissue regeneration and replacement.

Introduction: The challenge in tissue engineering lies in replicating the intricate structure of the native extracellular matrix. Recent advancements in AM, notably 3D printing, offer unprecedented capabilities to tailor scaffolds precisely, controlling properties like structure and bioactivity. CAD tools complement this by facilitating design using patient-specific data.

Area’s covered: This review introduces additive manufacturing (AM) and computer-aided design (CAD) as pivotal tools in advancing tissue engineering, particularly cartilage regeneration. This article explores various materials utilized in AM, focusing on polymers and hydrogels for their advantageous properties in tissue engineering applications. Integrating bioactive molecules, including growth factors, into scaffolds to promote tissue regeneration is discussed alongside strategies involving different cell sources, such as stem cells, to enhance tissue development within scaffold matrices.

Expert opinion: Applications of AM and CAD in addressing specific challenges like osteochondral defects and osteoarthritis in cartilage tissue engineering are highlighted. This review consolidates current research findings, offering expert insights into the evolving landscape of AM and CAD technologies in advancing tissue engineering, particularly in cartilage regeneration.

Introduction: Fungal infections, particularly those caused by Candida spp. have increased in recent years. A primary contributor to this surge was the COVID-19 pandemic, where many hospitalized patients had secondary fungal infections. Additionally, the emergence of resistant and multi-resistant fungal strains has become increasingly problematic due to the limited therapeutic options available in antifungal treatments.

Areas covered: This review presents a comprehensive analysis of recent studies focused on the development and characterization of lipid-based nanosystems as an emerging and promising therapeutic alternative. These systems have been evaluated for their potential to deliver antifungal agents specifically targeting resistant Candida spp. strains, offering a controlled and sustained release of drugs.

Expert opinion: Lipid-based nanomaterials are promising tools for the controlled and sustained release of drugs, particularly in treating Candida spp. infections. Although substantial research has been dedicated to development of these nanomaterials, only a few have reached clinical application, such as liposomal amphotericin B, for example. Therefore, it is critical to push forward with advancements to bring these nanomedicines into clinical practice, where they can contribute meaningfully to mitigating the challenge of resistant and lethal fungal strains.

Objective: This noninvasive study aimed to understand the interaction between shield-triggered autoinjectors (AI) and skin at the point of activation, hypothesizing that the AI's housing absorbs a significant amount of the user-applied force depending on shield design and skin characteristics.

Methods: Twenty-seven volunteers used a test device measuring applied force versus shield force and indentation depth relative to shield length (2,4,6,8 mm) in standing and sitting positions.

Results: Significant differences were found between applied and shield force for the different shield lengths. Shorter shields resulted in significantly lower force transfer coefficients, with means ranging from 0.72 for the 2 mm shield to 0.94 for the 8 mm shield. ANOVA revealed statistically significant factors (p < .05), including position and gender, with females generally having lower coefficient values. Indentation depth increased with higher forces and varied significantly between positions without significant shield length impact.

Conclusion: The findings confirm that an increase in shield length at the point of activation reduces skin friction with the housing, resulting in less force loss and a lower device activation force perceived by the user. Force loss can be further reduced by standing up. Understanding device-tissue interactions will support development of better AIs with fewer user failures.

Introduction: Nucleic acid (NA)-based therapeutics have shown great potential for downregulating or augmenting gene expression, and for promising applications, e.g., protein-replacement therapy and vaccination, a comprehensive understanding of the requirements for their targeted delivery to specific tissues or cells is needed.

Areas covered: In this review, we discuss clinical applications of four representative types of NA-based therapeutics, i.e. antisense oligonucleotides, small interfering RNA, messenger RNA, and circular RNA, with a focus on the lipid nanoparticle (LNP) technology used for intracellular delivery. The in vivo fate of LNPs is discussed to improve the understanding of trafficking of nanomedicines at the systemic and cellular levels. In addition, NA-based vaccines are discussed, focusing on targeting antigen-presenting cells and immune activation.

Expert opinion: Optimization of delivery systems for NA-based therapeutics is mainly focused on the standard requirements of prolonged systemic circulation and enhancing endosomal escape. Depending on the final destination in specific target tissues or cells, strategies should be adjusted to achieve the desired biodistribution of NA-based payloads. More studies relating to the pharmacokinetics of both cargo and carrier are encouraged, because their in vivo fates may differ, considering the possibility of premature cargo release before reaching the target.

Introduction: Nanoparticles (NPs) are widely used in the pharmaceutical field to treat various human disorders. Among these, lipid-based NPs (LNPs), including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), are favored for drug/bioactive delivery due to their high stability, biocompatibility, encapsulation efficiency, and sustained/controlled release. These properties make them particularly suitable as carriers of compounds derived from plant sources.

Areas covered: This study comprehensively explores updated literature knowledge on SLN and NLC, focusing on their composition and production methods for the specific delivery of drug/bioactive compounds derived from plant sources of interest in pharmaceutical and biomedical fields.

Expert opinion: SLN and NLC facilitate the development of more effective natural product-based therapies, aiming to reduce dosage and minimize side effects. These delivery systems align with the consumer demands for safer and more sustainable products, as there are also based on biocompatible and biodegradable raw materials, thereby posing minimal toxicological risks while also meeting regulatory guidelines.

Introduction: Myocardial infarction (MI) causes extensive structural and functional damage to the cardiac tissue due to the significant loss of cardiomyocytes. Early reperfusion is the standard treatment strategy for acute MI, but it is associated with adverse effects. Additionally, current therapies to alleviate pathological changes post-MI are not effective. Subsequent pathological remodeling of the damaged myocardium often results in heart failure. Oral drugs aimed at reducing myocardial damage and remodeling require repeated administration of high doses to maintain therapeutic levels. This compromises efficacy and patient adherence and may cause adverse effects, such as hypotension and liver and/or kidney dysfunction. Hydrogels have emerged as an effective delivery platform for orthotopic treatment of MI due to their high water content and excellent tissue compatibility.

Area covered: Hydrogels create an optimal microenvironment for delivering drugs, proteins, and cells, preserving their efficacy and increasing their bioavailability. Current research focuses on discovering functional hydrogels for mitigating myocardial damage and regulating repair processes in MI treatment.

Expert opinion: Hydrogels offer a promising approach in enhancing cardiac repair and improving patient outcomes post-MI. Advancements in hydrogel technology are poised to transform MI therapy, paving the way for personalized treatment strategies and enhanced recovery.

Introduction: Numerous purified bioactive compounds, crude extracts, and essential oils have demonstrated potent antioxidant, antimicrobial, anti-inflammatory, and antiviral properties, particularly in vitro or in silico; however, their in vivo applications are hindered by inadequate absorption and distribution in the organism. The incorporation of these phytochemicals into solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) has demonstrated significant advancements and represents a viable approach to improve their bioavailability through different administration routes.

Areas covered: This review discusses the potential applications of SLN and NLC, loading bioactive compounds sourced from plants for the treatment of several diseases. An overview of the preclinical developments on the use of these lipid nanoparticles is also provided as well as the requisites to be launched on the market.

Expert opinion: Medicinal plants have gained even more value for the pharmaceutical industries and their customers, leading to many studies exploring their therapeutic potential. Several bioactives derived from plants with antiviral, anticancer, neuroprotective, antioxidant, and antiaging properties have been proposed and loaded into lipid nanoparticles. In vitro and invivo studies corroborate the added value of SLN/NLC to improve the bioavailability of several bioactives. Surface modification to increase their stability and target delivery should be considering.

Introduction: Bladder Cancer is one of the most expensive cancers to treat due to its high cost of therapy as well as the surveillance expenses incurred to prevent disease recurrence and progression. Thus, there is a strong need to develop safe, efficacious drug formulations with controlled drug release profiles and tumor-targeting potential, for improved therapeutic outcomes of bladder cancer patients.

Areas covered: This review aims to provide an overview of drug formulations that have been studied for potential bladder cancer treatment in the last decade; highlight recent trends in bladder cancer treatment; mention ongoing clinical trials on bladder cancer chemotherapy; detail recently FDA-approved drug products for bladder cancer treatment and identify constraints that have prevented the translation of promising drug formulations from the research laboratory to the clinics.

Expert opinion: This work revealed that surface functionalization of particulate drug delivery systems and incorporating the nanoparticles into in situ gelling systems could facilitate controlled drug release for extended periods, and improve the prognosis of bladder cancer treatment. Future research directions could incorporate multiple drugs into the drug delivery systems to treat advanced stages of the disease. In addition, smart nanomaterials, including photothermal therapies, could be exploited to improve the therapeutic outcomes of bladder cancer patients.

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.