International Journal of Pharmaceutics最新文献

Semi-Solid Extrusion 3D printing (SSE 3DP) has emerged as a promising technology for fabricating oral drug formulations, offering significant opportunities for personalized medicine and tailored therapeutic outcomes. SSE 3DP is particularly advantageous for producing soft and chewable drug products and is well-suited for formulations containing thermosensitive drugs due to its low-temperature printing process. Among various 3D printing techniques, SSE 3DP holds considerable potential for point-of-care applications, enabling the on-demand production of patient-specific dosage forms. Despite these advantages, SSE 3DP faces certain limitations that affect its overall development and widespread adoption. This review provides a comprehensive overview of SSE 3DP's fundamental principles, current applications, and future prospects in oral drug delivery. It also addresses the challenges and limitations associated with SSE 3DP and examines the current outlook of this technique in oral drug delivery applications. An example of such a challenge is the lack of a harmonized method for evaluating rheological properties. To address this issue, the review describes a methodology for obtaining information related to extrudability and shape fidelity from rheological properties. Overall, this review aims to highlight the transformative potential of SSE 3DP in the pharmaceutical landscape, paving the way for tailored, and patient-centric therapies.

Korean red ginseng (KRG) extract is proposed for cosmetic use, but no data on biological effects of KRG-loaded vehicles exist. The study aimed to optimize new multi- and monophase vehicles for KRG extract delivery, assess their biocompatibility and evaluate their radical scavenging effect in vitro. Storage stability of oil-in-water nanoemulsions (NEs) and hydroalcoholic gels (2 % w/w KRG) was assessed over twelve weeks using dynamic light scattering, rheology and pH measurements. Release profiles of ginsenosides Rb1 (more hydrophilic) and Rg1 (moderately lipophilic) through a cellulose membrane were also investigated employing Franz diffusion cells. Antioxidant potential and biocompatibility were assessed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and cell viability assays. Vehicles remained stable over twelve weeks at 8 °C (NEs D_h stable, gel viscosity + 3.5 %). Diffusion studies showed higher release of Rg1 vs. Rb1 (7.10 vs. 1.39 µg/cm^-2 after 28 h). KRG-formulations demonstrated good biocompatibility with primary human dermal fibroblasts and HaCaT keratinocytes (72-94 % viability). Radical scavenging capacity of KRG extract did not differ between pure and incorporated form and was lower than that of a Hypericum extract or ascorbic acid. Results render KRG-formulations a potentially promising alternative to conventional antioxidants used in daily products.

Background: Osteosarcomas (OS) are malignant bone tumors prevalent in adolescents, characterized by aggressiveness and early metastasis. Current treatments including surgery and chemotherapy face challenges due to drug limitations and the complex tumor microenvironment (TME).

Methods: Tumour membranes (TM) derived from OS cells and macrophage membranes (MM) derived from macrophages were mixed to create hybrid membranes (HM), which were subsequently used to encapsulate microRNA-665(miR-665)-loaded Poly lactic-co-glycolic acid (PLGA) nanoparticles, forming HM@PLGA/miR-665 complexes. In vitro characterization included physical properties, colocalization studies, and assessment of macrophage polarization. In vivo experiments involved a nude mouse model to evaluate tumor targeting, biosafety, and therapeutic efficacy.

Results: The HM@PLGA/miR-665 complexes exhibited good physical characteristics and stability. In vitro, the complexes significantly altered the M1/M2 macrophage ratio, promoting M1 polarization and inhibiting M2 polarization. Macrophage supernatants from HM@PLGA/miR-665-treated cells inhibited proliferation, migration, and induced apoptosis in MG-63 osteosarcoma cells. In vivo, the complexes effectively targeted tumor tissues, showed good biosafety, and significantly inhibited OS progression, promoting tumor cell apoptosis and altering the M1/M2 macrophage ratio.

Conclusion: The HM@PLGA/miR-665 delivery system successfully targeted OS by modulating macrophages in the TME, exhibiting potential as a novel therapeutic strategy for OS.

In the present study, we introduce the concept of "transdermal sequential delivery" as a non-invasive and synergistic approach for the treatment of melanoma. We developed a functionalized Deep Eutectic System (DES) that incorporates both small molecule drugs and nanoparticles. The glycolysis inhibitor 2-deoxy-D-glucose (2-DG) served as the Hydrogen Bond Donor (HBD) to form the DES, while glutathione (GSH)-responsive Mesoporous Organosilicon Nanoparticles (MON) were prepared and encapsulated with chlorin e6 (Ce6). These nanoparticles were incorporated into the DES through surface-modified citric acid (CA) as a linker, resulting in the functionalized 2-DG DES-MON@Ce6 system. By leveraging the skin's barrier properties and the permeation-enhancing effects of the DES, both 2-DG and MON@Ce6 were delivered to the melanoma tissue in a sequential manner. Initially, 2-DG mitigated hypoxia and the immunosuppressive tumor microenvironment (TME) by disrupting glycolysis, thereby creating favorable conditions for the subsequent photodynamic therapy (PDT) effects of MON@Ce6 and enhancing immunogenic cell death (ICD). Consequently, the 2-DG DES-MON@Ce6 system demonstrated significant anti-tumor activity against melanoma within the context of the "transdermal sequential delivery" strategy. Overall, our functionalized DES-nano system facilitates the sequential transdermal delivery of drugs to melanoma, thereby maximizing the combination anti-tumor efficacy through a cascade reaction.

The therapeutic efficacy of drugs is highly dependent on their successful delivery to the target site. However, achieving targeted drug delivery to diseased areas remains a significant challenge. Current drug delivery systems based on nanocarriers often suffer from inefficiencies due to their lack of intrinsic propulsion and active targeting capabilities. Micro/nanomotors (MNMs), which are miniature machines capable of converting chemical or external energy into mechanical energy, offer a promising solution. Unlike traditional nanoparticles (NPs) that rely on passive diffusion through blood circulation, MNMs exhibit active locomotion, providing a significant advantage in future drug delivery applications. This review primarily focuses on the progress in research of MNMs in the realm of drug delivery. We present a succinct overview of MNMs and subsequently classify them based on their modes of mobility. Then we comprehensively summarize the applications of micro/nanomotor-based drug delivery systems in the treatment of various diseases, including cancer, bacterial infections, cardiovascular diseases, and others. Based on the current research status, we summarize the potential challenges, possible solutions, and prospect several key directions for future studies in active-targeted drug delivery using MNMs. Future research should focus on improving motor delivery efficiency, biosafety measures, productivity, and maneuverability.

As a new type of drug delivery system, microneedle have received extensive attention in wound healing due to their penetrability, painlessness, and high drug delivery efficiency. However, microneedle are often unable to penetrate the skin completely due to the limitations of the skin's mechanical properties, resulting in low drug delivery efficiency during wound repair. Therefore, it is particularly important to optimize the multi-level structural design of microneedles. This article systematically summarizes the multi-level structural design of microneedles that promote wound healing, including the structural parameters of a single microneedle, microneedle array design, and microneedle system structural optimization. It also summarizes the research progress on the functional design of microneedle systems at various stages of wound repair. This paper reviews the current status and limitations of microneedle patch design, and provides theoretical guidance for the design of smart microneedle wound management/healing.

High intraocular pressure (IOP) is the main risk factor for glaucoma progression. Acetazolamide (AZM) presents a potent IOP-lowering effect but is only administered orally due to its low aqueous solubility and ocular permeability. This study aimed to develop AZM nanocrystals (AZM-NC) as an alternative for its topical ocular delivery. AZM-NC were obtained by wet bead milling technique followed by spray drying, and a mixture design study was conducted to evaluate the optimal drug-to-stabilizer ratio regarding colloidal properties and stability. AZM-NC exhibited an average particle size of 299.73 ± 8.8 nm, a polydispersity index of 0.13 ± 0.01, and a zeta potential of -29.0 ± 0.9 mV, which remained mostly unchanged for at least 60 days when the dried powder was stored at room temperature. Fourier-transformed spectroscopy and powder X-ray diffraction analyses revealed no chemical or crystallinity changes in AZM-NC compared with AZM, respectively. Additionally, AZM-NC demonstrated increased drug saturation concentration, globular shapes, and higher adhesive properties than normal-sized AZM powder. Topical ocular administration of AZM-NC in albino male rabbits showed no clinical signs of ocular damage. Further, in vivo studies revealed a significant IOP reduction of up to 32 % of the basal IOP (-4.8 ± 1.2 mmHg, p < 0.05) in normotensive rabbit eyes (n = 7), after 4 h of AZM-NC suspension topical application, compared to groups treated with AZM suspension, normal saline solution and, AZOPT® (-1.8 ± 1.4 mmHg). Thus, AZM-NC could present a promising approach for developing an eye drop formulation for the localized management of glaucoma.