Expert opinion on drug delivery最新文献

Background: The primary aim was to assess the effectiveness and safety of three different algorithms of using steroids and inner ear catheter (INCAT) MED-EL® in partial deafness patients who underwent cochlear implantation. The secondary goal was the assessment of the impact of the depth of INCAT on hearing preservation after cochlear implantation.

Research design and methods: There were three algorithms of steroid administration: 1) methylprednisolone 62.5 mg/ml (solution), 3 patients; 2) methylprednisolone 40 mg/ml (suspension), 4 patients; 3) dexamethasone 4 mg/ml (solution), 3 patients. Pure tone audiometry (0.125-8 kHz) was performed preoperatively, 1 and 6 months post-op. Hearing preservation was assessed according to the HEARRING group formula. Impedance measurements were taken at two days, 1 and 6 months after surgery.

Results: Patients treated with methylprednisolone 40 mg/ml in suspension showed the best hearing preservation (50% complete and 50% partial preservation) 1 month post-op and later remained the most favorable. The lowest impedance was found in this group both 1 and 6 months post-op. A shorter INCAT insertion depth appeared to be more favorable than a longer one.

Conclusion: Our results suggest that patients treated with methylprednisolone 40 mg/ml (suspension) had better hearing outcomes compared to the other two medications.

Introduction: The low drug delivery rate of systemic chemotherapyto metastatic lymph nodes (LNs) may be due to tumor growth without tumorneovascularization in the LNs, loss of existing blood vessels and lymph sinusesdue to the tumor growth, and increased intranodal pressure. The lymphatic drugdelivery system (LDDS) is a method of injecting anticancer drugs directly intothe LNs and can overcome these problems. The world's first specific clinicalstudy using the LDDS for head and neck cancer started in 2024 in Japan. In thisreview, the background of the development of LDDS up to the present clinicaltrials is described.

Areas covered: The MXH10/Mo-lpr/lpr(MXH10/Mo/lpr) recombinant inbred model mouse, vascular and lymphatic flowthrough LNs, the clinical N0 (cN0) LN model, preclinical studies of the LDDS,and its clinical application to treat head and neck cancer.

Expert opinion: Conventionally, hematogenous and lymphatic administrationhave been the focus of attention for drug delivery to LNs. The LDDS is a methodfor injecting drugs directly to LNs, so it is important to develop a solventand injecting method that can increase the uniformity of drug distributionwithin LNs.

Introduction: The incorporation of 4D printing alongside chemical stimuli-responsive hydrogels represents a significant advancement in the field of biomedical engineering, effectively overcoming the constraints associated with conventional static 3D-printed structures. Through the integration of time as the fourth dimension, 4D printing facilitates the development of dynamic and adaptable structures that can react to chemical alterations in their surroundings. This innovation presents considerable promise for sophisticated tissue engineering and targeted drug delivery applications.

Areas covered: This review examines the function of chemical stimuli-responsive hydrogels within the context of 4D printing, highlighting their distinctive ability to undergo regulated transformations when exposed to particular chemical stimuli. An in-depth examination of contemporary research underscores the collaborative dynamics between these hydrogels and their surroundings, focusing specifically on their utilization in biomimetic scaffolds for tissue regeneration and the advancement of intelligent drug delivery systems.

Expert opinion: The integration of 4D printing technology with chemically responsive hydrogels presents exceptional prospects for advancements in tissue engineering and targeted drug delivery, facilitating the development of personalized and adaptive medical solutions. Although the potential is promising, it is essential to address challenges such as material optimization, biocompatibility, and precise control over stimuli-responsive behavior to facilitate clinical translation and scalability.

Introduction: Nucleic acid-based therapeutics have become a key pillar of the 'third wave' of modern medicine, following the eras of small molecule inhibitors and antibody drugs. Their rapid progress is heavily dependent on delivery technologies, with the development of N-acetylgalactosamine (GalNAc) conjugates marking a breakthrough in targeting liver diseases. This technology has gained significant attention for its role in addressing chronic conditions like chronic hepatitis B (CHB) and nonalcoholic steatohepatitis (NASH), which are challenging to treat with conventional methods.

Areas covered: This review explores the origins, mechanisms, and advantages of GalNAc-siRNA delivery systems, highlighting their ability to target hepatocytes via the asialoglycoprotein receptor (ASGPR). The literature reviewed covers preclinical and clinical advancements, particularly in CHB and NASH. Key developments in stabilization chemistry and conjugation technologies are examined, emphasizing their impact on enhancing therapeutic efficacy and patient compliance.

Expert opinion: GalNAc-siRNA technology represents a transformative advancement in RNA interference (RNAi) therapies, addressing unmet needs in liver-targeted diseases. While significant progress has been made, challenges remain, including restricted targeting scope and scalability concerns. Continued innovation is expected to expand applications, improve delivery efficiency, and overcome limitations, establishing GalNAc-siRNA as a cornerstone for future nucleic acid-based treatments.

Introduction: The advent of 3D printing has revolutionized biomedical engineering, yet limitations in creating dynamic human tissues remain. The emergence of 4D printing, which introduces time as a fourth dimension, offers new possibilities by enabling the production of adaptable, stimuli-responsive structures. A thorough literature search was performed across various databases, including Google Scholar, PubMed, Scopus, and Web of Science, to identify pertinent studies published up to 2025. The search parameters were confined to articles published in English that concentrated on peer-reviewed clinical studies.

Areas covered: This review explores the transition from 3D to 4D printing and focuses on stimuli-responsive materials, particularly hydrogels, which react to environmental changes. The literature search examined recent studies on the interaction of these materials with biological stimuli, emphasizing their application in tissue engineering and drug delivery applications.

Expert opinion: 4D printing, combined with smart materials, holds immense promise for advancing biomedical treatments, including customized therapies and regenerative medicine. However, technological challenges must be addressed to realize its full potential.

Introduction: Viral vectors have proven useful for delivering genetic information, such as drugs and vaccines, for therapeutic and prophylactic interventions. Self-amplifying RNA viruses possess the special feature of high-level RNA amplification in the host cell cytoplasm providing high antigen production against infectious pathogens and various types of cancers, and expression of anti-tumor genes, toxic genes, and immunostimulatory genes.

Areas covered: Self-amplifying RNA viral vectors have been evaluated in animal models and clinical trials for immune responses and protection against challenges with pathogenic infectious agents and tumor cells. Likewise, immune responses, tumor regression, and tumor eradication have been monitored in preclinical and clinical settings. The literature search used in the review is based on PubMed and clinical trial/biotechnology company websites up until September 2024.

Expert opinion: Self-amplifying RNA viruses have elicited strong immune responses and vaccine efficacy in animal models and humans leading to the approval of the vesicular stomatitis virus-based vaccine against Ebola virus disease in both the US and Europe. Moreover, therapeutic and prophylactic efficacy has been demonstrated in animal tumor models and cancer patients. Self-amplifying RNA viruses have also been evaluated in mouse models for neurological disorders.

Introduction: With the worldwide growing burden of respiratory tract infections (RTIs), innovative therapeutic approaches are in high demand. Inhaled antibodies (Abs) represent a promising avenue, offering targeted treatment options with potentially better therapeutic index compared to traditional delivery methods.

Areas covered: This comprehensive review summarizes the challenges faced in delivering Abs by (intranasal and pulmonary) inhalation. It outlines the physiological and biological barriers encountered by inhaled drugs, as well as the influence of delivery devices and formulation on the deposition and efficacy of inhaled molecules. Moreover, it provides a detailed overview of the current clinical trial landscape of inhaled anti-RTI Abs, highlighting the progress in the development of inhaled Abs targeting a range of pathogens, such as severe acute respiratory syndrome coronavirus 2 and respiratory syncytial virus. The mechanism of action, therapeutic targets, and clinical outcomes of these novel therapies are detailed.

Expert opinion: Delivery of Abs by inhalation faces several challenges. Addressing these challenges and developing specific approaches to deliver inhaled Abs represent a promising avenue for the development of the next generation of inhaled Abs. By offering targeted, localized therapy with the potential for a better therapeutic index, inhaled Abs could significantly improve outcomes for patients with RTIs.

Introduction: Bacteria and their derivatives show great potential as drug delivery systems due to their unique chemotaxis, biocompatibility, and targeting abilities. In CNS disease treatment, bacterial carriers can cross the blood-brain barrier (BBB) and deliver drugs precisely, overcoming limitations of traditional methods. Advances in genetic engineering, synthetic biology, and nanotechnology have transformed these systems into multifunctional platforms for personalized CNS treatment.

Areas covered: This review examines the latest research on bacterial carriers for treating ischemic brain injury, neurodegenerative diseases, and gliomas. Bacteria efficiently cross the blood-brain barrier via active targeting, endocytosis, paracellular transport, and the nose-to-brain route for precise drug delivery. Various bacterial drug delivery systems, such as OMVs and bacterial ghosts, are explored for their design and application. Databases were searched in Google Scholar for the period up to December 2024.

Expert opinion: Future developments in bacterial drug delivery will rely on AI-driven design and high-throughput engineering, enhancing treatment precision. Personalized medicine will further optimize bacterial carriers for individual patients, but challenges such as biosafety, immune rejection, and scalability must be addressed. As multimodal diagnostic and therapeutic strategies advance, bacterial carriers are expected to play a central role in CNS disease treatment, offering novel precision medicine solutions.

Introduction: Chronic non-healing wounds have emerged as a significant global healthcare challenge. Biofilm induced wound infections has been widely acknowledged. Despite the advanced understanding of biofilm formation, the existing approaches for diagnosing biofilms in wounds remain considerably suboptimal. Chemical signals produced by fungi to sense their environment, known as quorum sensing (QS) molecules are anticipated to cause revolution in non-healing wound antisepsis.

Areas covered: Biofilms render chronic wounds resistant to treatment and impede tissue repair by inducing chronic inflammation. QS is a biochemical signaling pathway that involves certain secreted molecules, namely phenylethanoids, indolyl, and sesquiterpene alcohols that can significantly minimize and obliterate bacterial biofilms if properly applied and released in wound treatments.

Expert opinion: QS molecules (QSMs) possess inhibitory properties that obstruct the formation of microbial biofilms and exhibit synergism with common antimicrobials. They can disrupt biofilms formed by drug-resistant microorganisms. The understanding of the current mechanisms and advancements in the utilization of QSMs within diverse drug delivery systems, and their release dynamics will be crucial in new drug design and delivery. Exploration of co-delivery of drugs alongside QS molecules, and assessing their impact on healing of chronic wounds before moving to clinical trials remain unaddressed.

Introduction: mRNA therapeutics were a niche area in drug development before COVID vaccines. They are now used in vaccine development, for non-viral therapeutic genome editing, in vivo chimeric antigen receptor T (CAR T) cell therapies and protein replacement.  mRNA is large, charged, and easily degraded by nucleases. It cannot get into cells, escape the endosome, and be translated to a disease-modifying protein without a delivery system such as lipid nanoparticles (LNPs).

Areas covered: This article covers how to design, select, and develop an LNP for therapeutic genome editing in the liver. The roadmap is divided into selecting the right LNP for discovery via a design, make, test, and analyze cycle (DMTA). The design elements are focused on ionizable lipids in a 4-component LNP, and insights are provided for how to set an in vitro and in vivo testing strategy. The second section focuses on transforming the LNP into a clinical drug product and covers formulation, analytical development, and process optimization, with brief notes on supply and regulator strategies.

Expert opinion: The perspective discusses the impact that academic-industry collaborations can have on developing new medicines for therapeutic genome editing in the liver. From the cited collaborations an enhanced understanding of intracellular trafficking, notably endosomal escape, and the internal structure of LNPs were attained and are deemed key to designing effective and safe LNPs. The knowledge gained will also enable additional assays and structural activity relationships, which would lead to the design of the next-generation delivery systems for nucleic acid therapies.