Expert Opinion on Drug Delivery最新文献

Introduction: Mucoadhesive drug delivery systems (MDDS) are specifically designed to interact and bind to the mucosal layer for localized, prolonged, and/or targeted drug delivery. Over the past 4 decades, different sites have been explored for mucoadhesion including the nasal, oral, and vaginal cavities, the gastrointestinal tract and ocular tissues.

Areas covered: The present review aims to provide a comprehensive understanding of different aspects of MDDS development. Part I focuses on the anatomical and biological aspects of mucoadhesion, which include a detailed elucidation of the structure and anatomy of the mucosa, the properties of mucin, the different theories of mucoadhesion and evaluation techniques.

Expert opinion: The mucosal layer presents a unique opportunity for effective localization as well as systemic drug delivery via MDDS. Formulation of MDDS requires a thorough understanding of the anatomy of mucus tissue, the rate of mucus secretion and turnover, and the physicochemical properties of mucus. Further, the moisture content and the hydration of polymers are crucial for interaction with mucus. A confluence of different theories used to explain the mechanism of mucoadhesion is useful for understanding the mucoadhesion of different MDDS and their evaluation is subject to factors, such as the site of administration, type of dosage form, and duration of action. [Figure: see text].

Introduction: Cancer vaccine represents a promising strategy toward personalized immunotherapy, and its therapeutic potency highly relies on the specificity of tumor antigens. Among these extensively studied tumor antigens, neoantigens, a type of short synthetic peptides derived from random somatic mutations, have been shown to be able to elicit tumor-specific antitumor immune response for tumor suppression. However, challenges remain in the efficient and safe delivery of neoantigens to antigen-presenting cells inside lymph nodes for eliciting potent and sustained antitumor immune responses. The rapid advance of biomaterials including various nanomaterials, injectable hydrogels, and macroscopic scaffolds has been found to hold great promises to facilitate the construction of efficient cancer vaccines attributing to their high loading and controllable release capacities.

Areas covered: In this review, we will summarize and discuss the recent advances in the utilization of different types of biomaterials to construct neoantigen-based cancer vaccines, followed by a simple perspective on the future development of such biomaterial-assisted cancer neoantigen vaccination and personalized immunotherapy.

Expert opinion: These latest progresses in biomaterial-assisted cancer vaccinations have shown great promises in boosting substantially potentiated tumor-specific antitumor immunity to suppress tumor growth, thus preventing tumor metastasis and recurrence.

Introduction: Vaccine technology has constantly advanced since its origin. One of these advancements is where purified parts of a pathogen are used rather than the whole pathogen. Subunit vaccines have no chance of causing disease; however, alone these antigens are often poorly immunogenic. Therefore, they can be paired with immune stimulating adjuvants. Further, subunits can be combined with delivery strategies such as nano/microparticles to enrich their delivery to organs and cells of interest as well as protect them from in vivo degradation. Here, we seek to highlight some of the more promising delivery strategies for protein antigens.

Areas covered: We present a brief description of the different types of vaccines, clinically relevant examples, and their disadvantages when compared to subunit vaccines. Also, specific preclinical examples of delivery strategies for protein antigens.

Expert opinion: Subunit vaccines provide optimal safety given that they have no risk of causing disease; however, they are often not immunogenic enough on their own to provide protection. Advanced delivery systems are a promising avenue to increase the immunogenicity of subunit vaccines, but scalability and stability can be improved. Further, more research is warranted on systems that promote a mucosal immune response to provide better protection against infection.

Objective: While interest in the use of wearable large-volume injectors for subcutaneous drug delivery is increasing, it remains unclear whether and under what conditions these emerging dosing options are preferred over more frequent but shorter administration of smaller doses using handheld autoinjectors. Therefore, the objective of this study was to examine the characteristics of patients diagnosed with cancer, diabetes, inflammatory and cardiovascular diseases, and treatment attributes that determine device preferences.

Methods: Based on a cross-sectional online choice experiment, 191 participants expressed their preferences without being physically exposed to the devices or performing injections. Logistic hierarchical regression models were used to assess which patient characteristics, and how changes in treatment attributes, drive device preferences.

Results: Participant quality of life reduced the likelihood of preferring wearable large-volume injectors to handheld autoinjectors. Moreover, reducing injection frequency from biweekly to monthly to quarterly injections, and shortening injection duration from 33 to 8 min, significantly increased the likelihood of patients preferring large-volume injectors to autoinjectors (p < 0.001).

Conclusion: The study revealed patient quality of life as predictor of device preference and identified critical inflection points in injection duration and injection frequency, at which patient preferences shift from handheld autoinjectors to wearable large-volume injectors.

Introduction: Ophthalmic diseases of the retina are a significant cause of vision loss globally. Despite much progress, there remains an unmet need for durable, long-acting treatment options. While biologic therapies show great promise, they present many challenges, including complexities in biochemical properties, mechanism of action, manufacturing considerations, preclinical evaluation, and delivery mechanism; these are confounded by the unique anatomy and physiology of the eye itself.

Areas covered: This review describes the current development status of intravitreally administered drugs for the treatment of ophthalmic disease, outlines the range of approaches that can be considered for sustained drug delivery to the eye, and discusses key preclinical considerations for the evaluation of ocular biologics.

Expert opinion: The required frequency of dosing in the eye results in a great burden on both patients and the health care system, with direct intraocular administration remaining the most reliable and predictable route. Sustained and controlled ophthalmic drug delivery systems will go a long way in reducing this burden. Sustained delivery can directly dose target tissues, improving bioavailability and reducing off-target systemic effects. Maintaining stability and activity of compounds can prevent aggregation and enable extended duration of release, while sustaining dosage and preventing residual polymer after drug depletion.

Objectives: The focus of the present research is to develop printlet formulations of pyrimethamine (PMT).

Methods: Printlets formulation of PMT were developed by screening design by varying laser scanning speed, Kollidon® VA 64, polyvinylpyrrolidone, and disintegrant.

Results: Laser scanning speed, Kollidon® VA, and disintegrant had statistically significant effect on hardness, disintegration time, and/or dissolution (p < 0.05). Dissolution was almost 100% in 30 min. X-ray powder diffraction indicated partial amorphous transformation of the crystalline drug. Pharmacokinetic and anti-toxoplasma activity profiles of the printlets and compressed tablets were superimposable with no statistical difference (p > 0.05).

Conclusion: Clinical performance of the printlets would be similar to the compressed tablets.

Introduction: Interest in nanomedicines has surged in recent years due to the critical role they have played in the COVID-19 pandemic. Nanoformulations can turn promising therapeutic cargo into viable products through improvements in drug safety and efficacy profiles. However, the developmental pathway for such formulations is non-trivial and largely reliant on trial-and-error. Beyond the costly demands on time and resources, this traditional approach may stunt innovation. The emergence of automation, artificial intelligence (AI) and machine learning (ML) tools, which are currently underutilized in pharmaceutical formulation development, offers a promising direction for an improved path in the design of nanomedicines.

Areas covered: the potential of harnessing experimental automation and AI/ML to drive innovation in nanomedicine development. The discussion centers on the current challenges in drug formulation research and development, and the major advantages afforded through the application of data-driven methods.

Expert opinion: The development of integrated workflows based on automated experimentation and AI/ML may accelerate nanomedicine development. A crucial step in achieving this is the generation of high-quality, accessible datasets. Future efforts to make full use of these tools can ultimately contribute to the development of more innovative nanomedicines and improved clinical translation of formulations that rely on advanced drug delivery systems.

Introduction: Messenger ribonucleic acid (mRNA) and small interfering RNA (siRNA) are biological molecules that can be heated, frozen, lyophilized, precipitated, or re-suspended without degradation. Currently, ionizable lipid nanoparticles (LNPs) are a promising approach for mRNA therapy. However, the long-term shelf-life stability of mRNA-ionizable LNPs is one of the open questions about their use and safety. At an acidic pH, ionizable lipids shield anionic mRNA. However, the stability of mRNA under storage conditions remains a mystery. Moreover, ionizable LNPs excipients also cause instability during long-term storage.

Area covered: This paper aims to illustrate why mRNA-ionizable LNPs have such a limited storage half-life. For the first time, we compile the tentative reasons for the short half-life and ultra-cold storage of mRNA-LNPs in the context of formulation excipients. The article also provided possible ways of prolonging the lifespan of mRNA-ionizable LNPs during long storage.

Expert opinion: mRNA-ionizable LNPs are the future of genetic medicine. Current limitations of the formulation can be overcome by an advanced drying process or a whole new hybrid formulation strategy to extend the shelf life of mRNA-ionizable LNPs. A breakthrough technology may open up new research directions for producing thermostable and safe mRNA-ionizable LNPs at room temperature.