Expert opinion on drug delivery最新文献

Introduction: Recent discoveries in the field of lung microbiota have enabled the investigation of new therapeutic interventions involving the use of inhaled probiotics.

Areas covered: This review provides an overview of what is known about the correlation between airway dysbiosis and the development of local and systemic diseases, and how this knowledge can be exploited for therapeutic interventions. In particular, the review focused on attempts to formulate probiotics that can be deposited directly on the airways.

Expert opinion: Despite considerable progress since the emergence of respiratory microbiota restoration as a new research field, numerous clinical implications and benefits remain to be determined. In the case of local diseases, once the pathophysiology is understood, manipulating the lung microbiota through probiotic administration is an approach that can be exploited. In contrast, the effect of pulmonary dysbiosis on systemic diseases remains to be clarified; however, this approach could represent a turning point in their treatment.

Introduction: Gemini surfactants (GS) are an elite class of amphiphilic molecules that have shown up as a potential candidate in the field of drug delivery because of their exceptional physicochemical properties. They comprise two hydrophilic headgroups connected by an adaptable spacer and hydrophobic tails that has shown promising results in delivering different therapeutic agents to cancer cells at preclinical level. However further studies are in demand to unlock the full potential of GS in this field.

Areas covered: This review summarizes the new advancements in GS as drug carriers in cancer therapy, their capacity to overcome conventional shortcomings and the demand for innovative approaches in disease treatment. A detailed list of GS-based formulations along with a brief description on oligomeric surfactants have also been provided in this review. This article summarizes data from studies identified through literature database searches including PubMed and Google Scholar (2010-2023).

Expert opinion: There are major challenges that need to be addressed in this field which restrict their progression toward clinical phase. Further research can focus on developing a theranostic system that can provide simultaneous real-time monitoring along with treatment care. Nevertheless, ensuring the safety parameters of these nanocarriers followed by their regulatory approval is a time-consuming and expensive process. A collaborative approach between regulatory bodies, research institutions, and pharmaceutical companies can speed up the process in the upcoming years.

Introduction: Microneedles (MNs) are miniaturized, painless, and minimally invasive platforms that have attracted significant attention over recent decades across multiple fields, such as drug delivery, disease monitoring, disease diagnosis, and cosmetics. Several manufacturing methods have been employed to create MNs; however, these approaches come with drawbacks related to complicated, costly, and time-consuming fabrication processes. In this context, employing additive manufacturing (AM) technology for MN fabrication allows for the quick production of intricate MN prototypes with exceptional precision, providing the flexibility to customize MNs according to the desired shape and dimensions. Furthermore, AM demonstrates significant promise in the fabrication of sophisticated transdermal drug delivery systems and medical devices through the integration of MNs with various technologies.

Areas covered: This review offers an extensive overview of various AM technologies with great potential for the fabrication of MNs. Different types of MNs and the materials utilized in their fabrication are also discussed. Recent applications of 3D-printed MNs in the fields of transdermal drug delivery and biosensing are highlighted.

Expert opinion: This review also mentions the critical obstacles, including drug loading, biocompatibility, and regulatory requirements, which must be resolved to enable the mass-scale adoption of AM methods for MN production, and future trends.

Introduction: Cancer vaccines (protein and peptide, DNA, mRNA, and tumor cell) have achieved remarkable success in the treatment of cancer. In particular, advances in the design and manufacture of biomaterials have made it possible to control the presentation and delivery of vaccine components to immune cells.

Areas covered: This review summarizes findings from major databases, including PubMed, Scopus, and Web of Science, focusing on articles published between 2005 and 2024 that discuss biomaterials in cancer vaccine delivery.

Expert opinion: The development of cancer vaccines is hindered by several bottlenecks, including low immunogenicity, instability of vaccine components, and challenges in evaluating their clinical efficacy. To transform preclinical successes into viable treatments, it is essential to pursue continued innovation, collaborative research, and address issues related to scalability, regulatory pathways, and clinical validation, ultimately improving outcomes against cancer.

Objective: Dissolving microneedles (DMNs) have shown great potential for transdermal drug delivery due to their excellent skin-penetrating ability and combination with nanocarriers (NCs) can realize targeted drug delivery. The objective of this study was to investigate the impact of microneedle dissolving rate on the in vivo fate of NC-loaded DMNs, which would facilitate the clinical translation of such systems.

Methods: Solid lipid nanoparticles (SLNs) were selected as the model NC for loading in DMNs, which were labeled by P4 probes with aggregation-quenching properties. Sodium hyaluronate acid (HA) and chitosan (CS), with different aqueous dissolving rates, were chosen as model tip materials. The effects of needle dissolving rate on the in vivo fate of NC-loaded DMNs was investigated by tracking the distribution of fluorescence signals after transdermal exposure.

Results: P4 SLNs achieved a deeper diffusion depth of 180 μm in DMN-HA with a faster dissolution rate, while the diffusion depth in DMN-CS with a slower dissolution rate was lower (140 μm). The in vivo experiments demonstrated that P4 SLNs had a T_1/2 value of 12.14 h in DMN-HA, whilst a longer retention time was found in DMN-CS, with a T_1/2 of 13.12 h.

Conclusions: This study confirmed that the in vivo diffusion rate of NC-loaded DMNs was determined by the dissolving rate of DMNs materials and provided valuable guidance for the design and development of NC-loaded DMNs in the future.

Background: Glaucoma is one of the major irreversible blinding eye diseases in the world. Reducing intraocular pressure (IOP) is the primary treatment option, and taking eye drops daily is the common method. However, short drug duration and poor bioavailability of eye drops may lead to unsatisfied therapeutic effects and inadequate patient compliance.

Methods: A brimonidine-loaded silicone rubber insert (BRI@SR@PT) was prepared by loading brimonidine into a surface-modified silicone rubber ring, followed by polydopamine/thermoplastic polyurethane coatings. The physical properties, in vitro cytocompatibility and drug release of BRI@SR@PT were investigated. The BRI@SR@PT was administrated in the conjunctival sac of rabbit eyes, and its in vivo drug release, IOP-lowering efficacy and biosafety were assessed.

Results: The BRI@SR@PT presented great thermal stability and excellent elasticity. The BRI@SR@PT was able to release BRI sustainably for 28 days with little toxicity in vitro. Compared to BRI eye drops, the BRI@SR@PT effectively lowered IOP for 21 days based on the sustained BRI release with great biosafety when administrated in conjunctival sac of rabbit eyes in a noninvasive fashion.

Conclusions: The conjunctival sac insert (BRI@SR@PT), as a promising drug-delivery platform, may provide a sustained IOP-lowering treatment for patients with ocular hypertension or glaucoma, without the need for invasive procedures.

Introduction: Understanding the interactions between administered nanoparticles and the liver is crucial for developing safe and effective nanomedicines. As the liver can sequester up to 99% of these particles due to its major phagocytic role, understanding these interactions is vital for clinical translation.

Areas covered: This review highlights recent studies on nanoparticle-liver interactions, including the influence of nanoparticle physicochemical properties on delivery, strategies to enhance delivery efficiency by modulating liver Kupffer cells, and their potential for treating certain hepatic diseases. Additionally, we discuss how aging impacts the liver's phagocytic functions.

Expert opinion: While liver accumulation can hinder nanomedicine safety and effectiveness, it also presents opportunities for treating certain liver diseases. A thorough understanding of nanoparticle-liver interactions is essential for advancing the clinical application of nanomedicines.

Introduction: Certainly, pancreatic ductal adenocarcinoma poses one of the greatest challenges in current oncology. The dense extracellular matrix and low vessel density in PDA tumor impede the effective delivery of drugs, primarily due to the short pharmacokinetics of most drugs and potential electrostatic interactions with stroma components.

Area covered: Owing to the distinctive metabolism of PDA and challenges in accessing nutrients, there is a growing interest in cell metabolism inhibitors as a potential means to inhibit cancer development. However, even if suitable combinations of inhibitors are identified, the question about their administration remains, as the same hindrances that impede effective treatment with conventional drugs will also hinder the delivery of inhibitors. Methods including nanotechnology to increase drugs in PDA penetrations are reviewed and discussed.

Expert opinion: Pancreatic cancer is one of the most difficult tumors to treat due to the small number of blood vessels, high content of extracellular matrix, and specialized resistance mechanisms of tumor cells. One possible method of treating this tumor is the use of metabolic inhibitors in combinations that show synergy. Despite promising results in in vitro tests, their effect is uncertain due to the tumor's structure. In the case of pancreatic cancer, priming of the tumor tissue is required through the sequential administration of drugs that generate blood vessels, increase blood flow, and enhance vascular permeability and extracellular matrix. The use of drug carriers with a size of 10-30 nm may be crucial in the therapy of this cancer.

Introduction: Dry powder inhaler (DPI) formulations are gaining attention as universal formulations with applications in a diverse range of drug formulations. The practical application of DPIs to pulmonary drugs requires enhancing their delivery efficiency to the target sites for various treatment modalities. Previous reviews have not explored the relation between particle morphology and delivery to different pulmonary regions. This review introduces new approaches to improve targeted DPI delivery using novel particle design such as supraparticles and metal-organic frameworks based on cyclodextrin.

Areas covered: This review focuses on the design of DPI formulations using polysaccharides, promising excipients not yet approved by regulatory agencies. These excipients can be used to design various particle morphologies by controlling their physicochemical properties and manufacturing methods.

Expert opinion: Challenges associated with DPI formulations include poor access to the lungs and low delivery efficiency to target sites in the lung. The restricted applicability of typical excipients contributes to their limited use. However, new formulations based on polysaccharides are expected to establish a technological foundation for the development of DPIs capable of delivering modalities specific to different lung target sites, thereby enhancing drug delivery.

Introduction: This review discusses novel hybrid assemblies that are based on liposomal formulations. The focus is on the hybrid constructs that are formed through the integration of liposomes/vesicles with other nano-objects such as nucleic acid nanostructures and metallic nanoparticles. The aim is to introduce some of the recent, specific examples that bridge different technologies and thus may form a new platform for advanced drug delivery applications.

Areas covered: We present selected examples of liposomal formulations combined with complex nanostructures either based on biomolecules like DNA origami or on metallic materials - metal/metal oxide/magnetic particles and metallic nanostructures, such as metal organic frameworks - together with their applications in drug delivery and beyond.

Expert opinion: Merging the above-mentioned techniques could lead to development of drug delivery vehicles with the most desirable properties; multifunctionality, biocompatibility, high drug loading efficiency/accuracy/capacity, and stimuli-responsiveness. In the near future, we believe that especially the strategies combining dynamic, triggerable and programmable DNA nanostructures and liposomes could be used to create artificial liposome clusters for multiple applications such as examining protein-mediated interactions between lipid bilayers and channeling materials between liposomes for enhanced pharmacokinetic properties in drug delivery.