Expert Opinion on Drug Delivery最新文献

Introduction: Transdermal drug delivery is limited by the stratum corneum, inhibiting the therapeutic potential of the permeants. Microneedles (MNs) have opened new frontiers in transdermal drug delivery systems. These micro-sized needles offer painless and accentuated delivery of drugs even with high molecular weights.

Areas covered: The review embodies drug delivery strategies with MNs with a description of MN types and fabrication techniques using various materials. The application of MN is not limited to drug delivery, but it also encompasses in vaccine delivery, diagnosis, phlebotomy, and even in the cosmetic industry. The review also tabulates MN-based marketed formulations. In a nutshell, we aim to present a panoramic view of MNs, including the design, applications, and regulatory aspects of MN.

Expert opinion: With the availability of numerous materials at the disposal of pharmaceutical scientists; the MN-based drug delivery technology has offered significant interventions toward the management of chronic maladies, including cardiovascular disorders, diabetes, asthma, mental depression, etc. As happens with any new technology, there are concerns with MN also such as biocompatibility issues with the material used for the fabrication. Nevertheless, the pharmaceutical industry must strive for preparing harmless, efficient, and cost-effective MN-based delivery systems for wider acceptance and patient compliance.

Introduction: RNA interference (RNAi) has demonstrated great potential in treating skin-related diseases, as small interfering RNA (siRNA) can efficiently silence specific genes. The design of skin delivery systems for siRNA is important to protect the nucleic acid while facilitating both skin targeting and cellular ingestion. Entrapment of siRNA into nanocarriers can accomplish these aims, contributing to improved targeting, controlled release, and increased transfection.

Areas covered: The siRNA-based nanotherapeutics for treating skin disorders are summarized. First, the mechanisms of RNAi are presented, followed by the introduction of challenges for skin therapy. Then, the different nanoparticle types used for siRNA skin delivery are described. Subsequently, we introduce the mechanisms of how nanoparticles enhance siRNA skin penetration. Finally, the current investigations associated with nanoparticulate siRNA application in skin disease management are reviewed.

Expert opinion: The potential application of nanotherapeutic RNAi allows for a novel skin application strategy. Further clinical studies are required to confirm the findings in the cell-based or animal experiments. The capability of large-scale production and reproducibility of nanoparticle products are also critical for translation to commercialization. siRNA delivery by nanocarriers should be optimized to attain cutaneous targeting without the risk of toxicity.

Background: Self-administration of subcutaneous interferon beta-1a (sc IFN β-1a) can be achieved with the RebiSmart® electromechanical autoinjector. This study investigated adherence to, and duration of persistence with, the newest version of the device (v1.6) among 2644 people receiving sc IFN β-1a for multiple sclerosis (MS).

Research design and methods: This retrospective, observational study utilized data from RebiSmart® devices, recorded on the MSdialog database, between January 2014 and November 2019. Adherence and persistence were evaluated over a 3-year period and assessed in relation to age, sex, injection type, and injection depth.

Results: The population of RebiSmart® users (N = 2644) comprised of 1826 (69.1%) females and mean age was 39 (range 16-83) years. Adherence to RebiSmart® use and data transfer to the MSdialog database was consistently high (mean 91.7%; range 86.8-92.6%), including across all variables (81.6-100%). Mean (±SD) persistence during the study period was 1.35 ± 1.06 years, with a maximum recorded persistence of 5.1 years. In multivariate analysis, the longest durations of persistence were observed among older individuals and males (p < 0.0001 and p = 0.0078, respectively).

Conclusions: People living with MS were highly adherent to use of the RebiSmart® device, with higher persistence generally observed for older and/or male individuals.

Introduction: The growing interest in subcutaneous delivery of larger single-dose volumes using handheld autoinjectors raises questions about the feasible upper limits for injection volume and rate. This review critically evaluates the literature on subcutaneous administration with dose volumes greater than 1.0 mL. In so doing, it examines how previous work has addressed limitations and considerations for designing and developing large-volume autoinjectors.

Areas covered: This article synthesizes 31 studies on large-volume subcutaneous delivery through a systematic review process and structures their findings based on three themes critical to developing large-volume autoinjectors: injection tolerability, suitability for self-administration, and pharmacokinetic equivalence with existing dosing options. This review highlights the answers provided by previous studies and identifies promising avenues for future research.

Expert opinion: This review finds that the literature supports the feasibility of delivering single large-dose subcutaneous volumes, providing a foundation for large-volume autoinjectors. Moreover, the review guides future research to address questions within and across themes critical to large-volume autoinjector development, helping to provide health-care professionals and patients with more effective and convenient dosing options.

Introduction: The skin is an attractive route for drug delivery. However, the stratum corneum is a critical limiting barrier for drug permeation. Nanoentrapment is a way to enhance cutaneous drug delivery, by diverse mechanisms, with a notable trend of nanoparticles accumulating into the hair follicles when topically applied. Iontophoresis is yet another way of increasing drug transport by applying a mild electrical field that preferentially passes through the hair follicles, for being the pathway of lower resistance. So, iontophoresis application to nanocarriers could further increase actives accumulation into the hair follicles, impacting cutaneous drug delivery.

Areas covered: In this review, the authors aimed to discuss the main factors impacting iontophoretic skin transport when combining nanocarriers with iontophoresis. We further provide an overview of the conditions in which this combination has been studied, the characteristics of nanosystems employed, and hypothesize why the association has succeeded or failed to enhance drug permeation.

Expert opinion: Nanocarriers and iontophoresis association can be promising to enhance cutaneous drug delivery. For better results, the electroosmotic contribution to the iontophoretic transport, mainly of negatively charged nanocarriers, charge density, formulation pH, and skin models should be considered. Moreover, the transfollicular pathway should be considered, especially when designing the nanocarriers.

Introduction: Microneedle fabrication was conceptualized in the 1970s as devices for painless transdermal drug delivery. The last two decades have seen considerable research and financial investment in this area with SARS-CoV-2 and other vaccines catalyzing their application to in vivo intradermal vaccine delivery. Microneedle arrays have been fabricated in different shapes, geometries, formats, and out of different materials.

Areas covered: The recent pandemic has offered microneedle platforms the opportunity to be employed as a vehicle for SARS-CoV-2 vaccine administration. Various modes of vaccination delivery and the potential of microneedle array-based vaccines will be presented, with a specific focus placed on recent SARS-CoV-2 research. The advantages of microneedle-based vaccine administration, in addition to the major hurdles to their en masse implementation, will be examined.

Expert opinion: Considering the widely acknowledged disadvantages of current vaccine delivery, such as anxiety, pain, and the requirement for professional administration, a large shift in this research sphere is imminent. The SARS-CoV-2 pandemic has catalyzed the development of alternate vaccination platforms, working to avoid the requirement for mass vaccination centers. As microneedle vaccine patches are transitioning through clinical study phases, research will be required to prepare this technology for a more mass production environment.

Introduction: Tranexamic acid is used for the treatment of hyperpigmentation, and the topical route is the most favorable route for its administration. Tranexamic acid lowers plasmin and tyrosinase, which reduces melanin and skin hyperpigmentation. Low penetration through the outer layer of skin and low availability at target melanocyte cells limit tranexamic acid topical administration. Different novel delivery systems like liposomes, microneedles, topical beads, and microparticles can help in overcoming these limitations.

Areas covered: The mechanism of action of tranexamic acid and novel delivery systems for its topical delivery have been discussed. Further, patents related to the topical delivery of tranexamic acid and clinical trials undertaken to analyze their potential have been discussed.

Expert opinion: Targeting tranexamic acid in the epidermal layer makes more amount of drug available for action on melanocytes, the target site for tranexamic acid. Novel drug delivery formulations like liposomes, solid lipid nanoparticles, nano-lipidic carriers, and topical beads have the potential of achieving epidermal targeting. Epidermal targeting of tranexamic acid can help in the superior delivery of the drug, making its topical treatment more efficient.

Introduction: Skin cancer is the most common form of cancer worldwide, with increasing incidence rates in recent years. Although conventional chemotherapy and radiation therapy have been used for its treatment, these therapies have several limitations such as lack of selectivity and significant side effects. Targeted nanocarriers have emerged as a promising approach for the treatment of skin cancer.

Areas covered: This review article provides an overview of targeted nanocarriers for skin cancer treatment. It covers the various types of targeted nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles.

Expert opinion: There are still several challenges that need to be addressed before the clinical translation of targeted nanoparticles, such as optimization of their properties, development of reliable and robust characterization methods, and evaluation of their safety and efficacy in clinical trials. Another key aspect for the advancement of these studies is the need to improve regulatory aspects related to the toxicity and regulation of nanomedicines targeting skin cancer. Overall, targeted nanocarriers hold great potential for the development of safe and effective treatments for skin cancer, which can contribute to a better prognosis and overall patients' life quality.

Introduction: For decades, finding effective long-term or disease-modifying treatments for skin disorders has been a major focus of scientists. The conventional drug delivery systems showed poor efficacy with high doses and are associated with side effects, which lead to challenges in adherence to therapy. Therefore, to overcome the limitations of conventional drug delivery systems, drug delivery research has focused on topical, transdermal, and intradermal drug delivery systems. Among all, the dissolving microneedles have gained attention with a new range of advantages of drug delivery in skin disorders such as breaching skin barriers with minimal discomfort and its simplicity of application to the skin, which allows patients to administer it themselves.

Areas covered: This review highlighted the insights into dissolving microneedles for different skin disorders in detail. Additionally, it also provides evidence for its effective utilization in the treatment of various skin disorders. The clinical trial status and patents for dissolving microneedles for the management of skin disorders are also covered.

Expert opinion: The current review on dissolving microneedles for skin drug delivery is accentuating the breakthroughs achieved so far in the management of skin disorders. The output of the discussed case studies anticipated that dissolving microneedles can be a novel drug delivery strategy for the long-term treatment of skin disorders.