Expert opinion on drug delivery最新文献

Introduction: Solid dosage forms face the risk of the Maillard reaction during development and storage. This reaction occurs between reducing excipients and amino-group-containing drugs, potentially leading to discoloration, impurity formation, and degradation of active ingredients, significantly impacting product quality and excipient selection.

Areas covered: Using lactose, a representative reducing excipient, as an example, this article systematically explores the mechanisms, influencing factors, control strategies, and potential applications of the Maillard reaction in solid dosage forms. It aims to provide theoretical support and practical guidance for formulation optimization, quality control, and innovative development of pharmaceutical preparations. Searches of Google Scholar and PubMed were undertaken to gather the literature included in this review.

Expert opinion: The Maillard reaction between lactose and amino-group-containing drugs poses a significant quality risk, directly affecting the stability and safety of pharmaceutical preparations. In generic drug development, controlling this reaction is a critical step in achieving consistency with the reference listed drug (RLD). Instead of simply avoiding lactose, a proactive strategy should be adopted early in development. Through compatibility assessment, mechanistic studies, and comprehensive control measures, this challenge can be transformed into an opportunity for formulation optimization and innovation, thereby advancing the development of high-quality solid dosage forms.

Introduction: Due to its unique anatomical and physiological properties, the liver is known to capture the prevailing amount of intravenously administered nanoparticles. However, selectively delivering them to hepatocytes, the primary cells affected in most liver diseases, remains challenging, as nanoparticles are predominantly internalized by Kupffer cells, triggering inflammatory responses and fibrosis. Iron oxide nanoparticles can be engineered for active hepatocyte targeting via surface ligand modification, taking into account the nanoparticle size.

Areas covered: This review covers the interactions between iron oxide nanoparticles, Kupffer cells, hepatic stellate cells, and hepatocytes. Iron oxide nanoparticles may induce hepatocellular toxicity through mechanisms such as oxidative stress, lysosomal and mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy impairment. Furthermore, iron metabolism and some proteins involved in the regulation of iron homeostasis are also addressed. The role of the Z-potential, size, and surface modification of nanoparticles were analyzed from the point of view of their uptake by liver cells. The corona and margination effects for iron oxide nanoparticles were considered.

Expert opinion: Iron oxide nanoparticles hold significant potential for targeted hepatocyte delivery, provided that their physicochemical properties are carefully optimized to minimize off-target uptake by Kupffer cells and reduce hepatotoxicity. A comprehensive understanding of nanoparticle - cell interactions, iron homeostasis, and the impact of surface engineering is essential for the rational design of safer and more effective nanocarriers. Future progress will depend on balancing hepatocyte-specific targeting with biocompatibility, enabling the translational application of iron oxide nanoparticles in the diagnosis and treatment of liver diseases.

Introduction: The ideal Drug delivery systems (DDS) should be able to effectively and efficiently deliver the drugs to the targeted tissue or cells, releasing them at a desired rate while retaining their bioactivity. However, most DDS have some drawbacks, such as burst release, limited drug accumulation in the target organs, as well as off-target toxicity.

Areas covered: Nanolipogels or NLGs, which consist of a crosslinked core surrounded by a lipid membrane, are continuing to find applications in sustained drug delivery. The core is usually made of a polymer that is chemically crosslinked via the use of UV light or via ionic crosslinking. Studies have shown that varying the crosslink density of the core accomplishes two things: preventing leakage of cargo from the core; and entry into target cells without collapse of the NLG. Applications such as sustained siRNA delivery as well as targeted CRISPR delivery have been reported.

Expert opinion: To date no clinical trial has been reported for NanoLipoGels, and the drug/gene delivery applications are currently in the pre-clinical stage. More work directed toward selective targeting using NLGs is warranted, as is a more systematic approach toward the mechanism of cellular uptake. These foundational research steps are essential for advancing the technologies and accelerating the translation to the clinical stage.

Introduction: Bi-gels are a novel drug delivery system that enhances the regulated and targeted release of anticancer therapies by combining hydrogels and organogels. These dual-phase systems, including a hydrophilic polymer network (hydrogel) and a lipophilic polymer network (organogel), enable the simultaneous administration of hydrophilic and lipophilic pharmaceuticals. In bi-gels, the aqueous and organic phases provide complementary functions.

Areas covered: This study examines the principles of bi-gels, encompassing their definition, composition, gelation processes, and preparation techniques. It emphasizes the design and formulation techniques for cancer treatment, concentrating on polymeric materials, phase roles, and encapsulation parameters. The discussion encompasses targeting strategies including passive mechanisms (EPR effect), active mechanisms (ligand-receptor interactions), and response to the tumor microenvironment. Applications in oncology, namely bi-gel systems treating cutaneous malignancies, are highlighted. The review combines formulation science with therapeutic targeting to introduce bi-gels as potential platforms for regulated drug delivery and improved anticancer effectiveness.

Expert opinion: Bi-gels are sophisticated dual-phase drug carriers created by several gelation processes. They facilitate efficient encapsulation, phase-controlled delivery, and tumor-specific targeting via ligand interactions and microenvironment sensitivity, presenting promising applications in cancer therapy with improved precision and bioavailability.

Introduction: Pain is a widespread global health issue, significantly affecting quality of life and contributing to disability. It is estimated that between 20% and 30% of the global population suffer from some form of non-cancer chronic pain. Around 80% of surgical patients report postoperative acute pain, with less than 50% achieving adequate pain control. Despite these statistics, the management of pain still remains a significant challenge for clinicians, with many patients experiencing poorly controlled pain or adverse effects related to analgesic medication.

Areas covered: This literature review outlines current pain management strategies, focusing on non-oral postoperative pain therapies, including injectable drug delivery systems (such as in situ forming implants, micro- and nano-based formulations) and implantable drug delivery systems. Emphasis is placed on solid implantable devices designed for sustained drug delivery, which can offer more efficient localized drug delivery at the pain site.

Expert opinion: While pharmacological treatments, including oral opioids and nonsteroidal anti-inflammatory drugs, are commonly used, implantable controlled release systems are emerging as more effective alternatives. These systems provide localized pain relief with reduced systemic exposure, minimizing side effects, opioid use, and the risk of addiction, offering a promising solution for improved postoperative pain management.

Introduction: Nose-to-brain drug delivery provides a promising noninvasive route to bypass the blood-brain barrier through direct nasal cavity-brain connections. Therapeutic agents reach the central nervous system via systemic circulation or olfactory/trigeminal nerve pathways. Only the olfactory epithelium enables direct brain transport through olfactory neurons, bypassing the blood-brain barrier, while the respiratory epithelium primarily supports systemic absorption before CNS access via trigeminal nerves.

Areas covered: This review examines anatomical and functional differences between olfactory and respiratory epithelia, focusing on receptor, lectin, microbial, and enzymatic expression variations, particularly species-specific differences. These distinctions create opportunities for selective olfactory epithelium targeting. Key studies using formulation strategies and physical delivery methods to enhance olfactory-specific drug delivery are discussed, alongside analytical techniques for assessing olfactory accumulation. A systematic literature search across major databases through June 2025 supports these findings.

Expert opinion: Despite decades of research, nose-to-brain drug delivery faces unresolved challenges. Major limitations include imprecise targeting of the olfactory epithelium and the lack of standardized in vitro and in vivo models for determining exact transport mechanisms and enabling cross-comparisons. Addressing these gaps is essential for advancing targeted nose-to-brain drug delivery systems.

Introduction: Amygdalin, is arguably, one of the most controversial molecules found in nature, with several therapeutic properties, including anticancer, but there are concerns over its toxicity in healthy tissue alike, which warrants a modified approach toward its utilization in therapy.

Areas covered: This review examines a rational approach toward its effective deployment in managing several diseases, anticancer, and anti-fibrotic, anti-inflammatory effects. The search for relevant articles was conducted by scouting the PubMed and Scopus on published articles from 2014-2025. We capture the key modulatory pathways of amygdalin that conveys several of its therapeutic effects and paradoxically, the observed toxicity in healthy tissue. The review contends that amygdalin remains as a formidable therapeutic contender for treating several diseases, if the dose can be attenuated through controlled release from nanotechnological-based formulation.

Expert opinion: Toxicity concerns and stability associated with amygdalin are best addressed through slow and controlled release from nano-encapsulation delivery systems. A further frontier can involve co or trio- nano-encapsulation of amygdalin with other therapeutic agents, whereby toxicity concerns and drug resistance are simultaneously addressed.

Introduction: Deferoxamine (DFO) is an iron-chelator, approved for systemic treatment of iron overload. New research finds local applications to mechanistically correct ischemia-driven hypoxia that underlies chronic wound pathology resulting in therapeutic angiogenesis. Development of composite hydrogels and hybrid biomaterials that combine natural and synthetic polymers for enhanced mechanical integrity, antimicrobial function, and controlled drug release confirms that the field is moving toward multifunctional, bio-responsive wound therapies. Incorporating deferoxamine via reverse-micelle technology in a Deferoxamine Intradermal Delivery Patch (DIDP) advances this field by integrating a clinically approved, mechanistically targeted drug within a biocompatible matrix supported by preclinical safety and translational feasibility.

Areas covered: We review transdermal application of deferoxamine and current biomaterials that enable dermal penetration of hydrophilic drugs. We discuss the first-ever in-human clinical application of DIDP and scarcity of clinical trials. Furthermore, we outline necessary steps for broad implementation of DIDP and explore potential future applications, including combination therapies.

Expert opinion: Deferoxamine provides a remarkable ability to induce therapeutic angiogenesis despite diabetes or increased age, and this therapy could be utilized for other diseases that impair wound healing such as autonomic skin dysfunction following complete spinal cord injury. We identify efforts to increase the long-term safety profiles and advocate for large-scale randomized clinical trials.