Expert opinion on drug delivery最新文献

Background: This article presents a strategy that a Drug Delivery Device Developer (DDDD) has adopted to support Abbreviated New Drug Application (ANDA) submissions of drug-device combination products. As per the related FDA guidance, a threshold analysis should be compiled. If 'other differences' between the Reference Listed Drug (RLD) and the generic drug devices are identified, a Comparative Use Human Factors (CUHF) study may be requested.

Methods: The DDDD performed task analysis and physical comparison to assess the pen injector design differences. Then, a formative CUHF study with 25 participants simulating injections using both RLD and the generic pen injectors was conducted.

Results: After each participant completed four simulated injections, similar type and rates of use error between the RLD (0.70) and generic (0.68) pen injectors were observed.

Conclusion: DDDDs can support pharmaceutical companies in the ANDA submission strategy of their drug-device combination product by initiating comparative task analysis and physical comparison of the device as inputs for the threshold analysis. If 'other differences' are identified, a formative CUHF study can be performed. As shown in our case study, this approach can be leveraged to support the sample size calculation and non-inferiority margin determination for a CUHF study with the final combination product.

Introduction: The prodrug approach has been thought to be a simple solution to improve brain drug delivery for decades. Nevertheless, it still comes as a surprise that there is relatively little success in the field. The best example anti-parkinsonian drug levodopa has been serendipitously discovered to be a transporter-utilizing brain-delivered prodrug rather than a rationally developed one.

Areas covered: The lack of success can mainly be explained by the insufficient understanding of the role of membrane proteins that can facilitate drug delivery at dynamic barriers, such as the blood-brain barrier (BBB), but also by the sparse knowledge of prodrug bioconverting enzymes in the brain. This review summarizes the current status of the prodrug attempts that have been developed in the past to improve brain drug delivery.

Expert opinion: With the expandingly improved analytical and computational technologies, it is anticipated that enhanced brain drug delivery will be eventually achieved for most of the central nervous system (CNS) acting drugs. However, this requires that carrier-mediated (pro)drug delivery methods are implemented in the very early phases of the drug development processes and not as a last step to survive a problematic investigational drug candidate.

Background: Controlled and targeted drug delivery to treat nonalcoholic fatty liver disease (NAFLD) can benefit from additive attributes of natural formulation ingredients incorporated into the drug delivery vehicles.

Methods: Lovastatin (LVN) loaded, bile acid (BA) and fatty acid (FA) integrated nanoemulsomes (NES) were formulated by thin layer hydration technique for synergistic and targeted delivery of LVN to treat NAFLD. Organic phase NES was comprised of stearic acid with garlic (GL) and ginger (GR) oils, separately. Ursodeoxycholic acid and linoleic acid were individually incorporated as targeting moieties.

Results: Stability studies over 90 days showed average NES particle size, surface charge, polydispersity index, and entrapment efficiency values of 270 ± 27.4 nm, -23.8 ± 3.5 mV, 0.2 ± 0.04 and 81.36 ± 3.4%, respectively. Spherical NES were observed under a transmission electron microscope. In-vitro LVN release depicted non-fickian release mechanisms from GL and GR oils-based NES. Ex-vivo permeation of BA/FA integrated NES through isolated rat intestines showed greater flux than non-integrated ones.

Conclusion: Liver histopathology of experimental rats together with in-vivo lipid profiles and liver function tests illustrated that these NES possess the clinical potential to be promising drug carriers for NAFLD.

Introduction: Epilepsy, a prevalent neurodegenerative disorder, profoundly impacts the physical and mental well-being of millions globally. Historically, antiseizure drugs (ASDs) have been the primary treatment modality. However, despite the introduction of novel ASDs in recent decades, a significant proportion of patients still experiences uncontrolled seizures.

Areas covered: The rapid advancement of nanomedicine in recent years has enabled precise targeting of the brain, thereby enhancing therapeutic efficacy for brain diseases, including epilepsy.

Expert opinion: Nanomedicine holds immense promise in epilepsy treatment, including but not limited to enhancing drug solubility and stability, improving drug across blood-brain barrier, overcoming resistance, and reducing side effects, potentially revolutionizing clinical management. This paper provides a comprehensive overview of current epilepsy treatment modalities and highlights recent advancements in nanomedicine-based drug delivery systems for epilepsy control. We discuss the diverse strategies used in developing novel nanotherapies, their mechanisms of action, and the potential advantages they offer compared to traditional treatment methods.

Introduction: Novel injectables possess applications in both local and systemic therapeutics delivery. The advancement in utilized materials for the construction of complex injectables has tremendously upgraded their safety and efficacy.

Areas covered: This review focuses on various strategies to produce novel injectables, including oily dispersions, in situ forming implants, injectable suspensions, microspheres, liposomes, and antibody-drug conjugates. We herein present a detailed description of complex injectable technologies and their related drug formulations permitted for clinical use by the United States Food and Drug Administration (USFDA). The excipients used, their purpose and the challenges faced during manufacturing such formulations have been critically discussed.

Expert opinion: Novel injectables can deliver therapeutic agents in a controlled way at the desired site. However, several challenges persist with respect to their genericization. Astronomical costs incurred by innovator companies during product development, complexity of the product itself, supply limitations with respect to raw materials, intricate manufacturing processes, patent evergreening, product life-cycle extensions, relatively few and protracted generic approvals contribute to the exorbitant prices and access crunch. Moreover, regulatory guidance are grossly underdeveloped and significant efforts have to be directed toward development of effective characterization techniques.

Introduction: Intranasal administration is an effective drug delivery routes in modern pharmaceutics. However, unlike other in vivo biological barriers, the nasal mucosal barrier is characterized by high turnover and selective permeability, hindering the diffusion of both particulate drug delivery systems and drug molecules. The in vivo fate of administrated nanomedicines is often significantly affected by nano-biointeractions.

Areas covered: The biological barriers that nanomedicines encounter when administered intranasally are introduced, with a discussion on the factors influencing the interaction between nanomedicines and the mucus layer/mucosal barriers. General design strategies for nanomedicines administered via the nasal route are further proposed. Furthermore, the most common methods to investigate the characteristics and the interactions of nanomedicines when in presence of the mucus layer/mucosal barrier are briefly summarized.

Expert opinion: Detailed investigation of nanomedicine-mucus/mucosal interactions and exploration of their mechanisms provide solutions for designing better intranasal nanomedicines. Designing and applying nanomedicines with mucus interaction properties or non-mucosal interactions should be customized according to the therapeutic need, considering the target of the drug, i.e. brain, lung or nose. Then how to improve the precise targeting efficiency of nanomedicines becomes a difficult task for further research.

Introduction: Central nervous system (CNS)-related disorders are increasingly being recognized as a global health challenge worldwide. There are significant challenges for effective diagnosis and treatment due to the presence of the CNS barriers which impede the management of neurological diseases. Combination of nanovesicles (NVs) and magnetic nanoparticles (MNPs), referred to as magnetic nanovesicles (MNVs), is now well suggested as a potential theranostic option for improving the management of neurological disorders with increased targeting efficiency and minimized side effects.

Areas covered: This review provides a summary of major CNS disorders and the physical barriers limiting the access of imaging/therapeutic agents to the CNS environment. A special focus on the unique features of MNPs and NV is discussed which make them attractive candidates for neuro-nanomedicine. Furthermore, a deeper understanding of MNVs as a promising combined strategy for diagnostic and/or therapeutic purposes in neurological disorders is provided.

Expert opinion: The multifunctionality of MNVs offers the ability to overcome the CNS barriers and can be used to monitor the effectiveness of treatment. The insights provided will guide future research toward better outcomes and facilitate the development of next-generation, innovative treatments for CNS disorders.

Background: Chemo-immunotherapy modifies the tumor microenvironment to enhance the immune response and improve chemotherapy. This study introduces a dual-armed chemo-immunotherapy strategy combating breast tumor progression while re-polarizing Tumor-Associated Macrophage (TAM) using prodigiosin-loaded mannan-coated magnetic nanoparticles (PG@M-MNPs).

Methods: The physicochemical properties of one-step synthetized M-MNPs were analyzed, including X-ray diffraction, FTIR, DLS, VSM, TEM, zeta potential analysis, and drug loading content were carried out. Biocompatibility, cancer specificity, cellular uptake, and distribution of PG@M-MNPs were investigated using fluorescence and confocal laser scanning microscopy, and flow cytometry. Furthermore, the expression levels of IL-6 and ARG-1 after treatment with PG and PG@M-MNPs on M1 and M2 macrophage subsets were studied.

Results: The M-MNPs were successfully synthesized and characterized, demonstrating a size below 100 nm. The release kinetics of PG from M-MNPs showed sustained and controlled patterns, with enzyme-triggered release. Cytotoxicity assessments revealed an enhanced selectivity of PG@M-MNPs against cancer cells and minimal effects on normal cells. Additionally, immuno-modulatory activity demonstrates the potential of PG@M-MNPs to change the polarization dynamics of macrophages.

Conclusion: These findings highlight the potential of a targeted approach to breast cancer treatment, offering new avenues for improved therapeutic outcomes and patient survival.