Jul 2026· International journal of pharmaceutics· Vol 702, pp.
127180
· 0 citations· 66 references
Medicine
TL;DR
In vivo antitumor studies in CT-26 tumor-bearing mice showed a marked reduction in relative tumor volume and a tumor inhibition rate (TIR) of 70.57%, with stable body weight and no histopathological abnormalities in liver and kidney tissues (H&E), indicating minimal systemic toxicity.
Abstract
Localized drug delivery using nanofiber-based systems enables precise and sustained release of chemotherapeutics at tumor sites. In this study, a novel pH-responsive core-shell nanofiber incorporating 5-FU@ZIF-8 was fabricated by o/w emulsion electrospinning using Zein/PVP and black seed oil. SEM analysis confirmed a uniform core-shell morphology (average diameter: 795 ± 16 nm). The 5-FU@ZIF-8-loaded nanofiber (5-FU@ZIF-8 NF) exhibited favorable surface hydrophilicity (39.0° ± 0.7°) and tensile strength (2.07 ± 0.1 MPa). In vitro results demonstrated high biocompatibility (∼90% L929 cell viability) and potent antitumor activity (∼70% CT-26 cytotoxicity), accompanied by increased ROS generation and reduced cell migration. Antibacterial evaluation revealed strong inhibitory activity of 5-FU@ZIF-8 NF against Staphylococcus aureus (55% inhibition), whereas free 5-FU exhibited greater activity against Escherichia coli. In vivo antitumor studies in CT-26 tumor-bearing mice showed a marked reduction in relative tumor volume (RTV ≈ 5 on day 18) and a tumor inhibition rate (TIR) of 70.0 ± 6.57%, with stable body weight and no histopathological abnormalities in liver and kidney tissues (H&E), indicating minimal systemic toxicity. This implantable system offers a precise, localized therapeutic approach with enhanced efficacy and reduced side effects compared to conventional chemotherapy.
Zeolitic imidazolate framework-8 (ZIF-8) is a promising nanocarrier for drug delivery due to its tunable porosity, biocompatibility, and pH sensitivity. In this study, a one-pot room-temperature synthesis strategy was developed to encapsulate polydatin (PD) within ZIF-8 (PD@ZIF-8), followed by chitosan (CS) coating (PD@ZIF-8/CS) for improved stability and sustained release of this drug delivery system. FTIR, UV-vis, XRD, DLS and TGA characterization confirmed the successful synthesis of PD@ZIF-8/CS. SEM micrographs revealed the rhombic dodecahedral particles (85.2 nm) of ZIF-8, slightly roughened polyhedral particles (115.4 nm) of PD@ZIF-8 and aggregated particles (294.8 nm) of PD@ZIF-8/CS, confirming CS shell formation. DLS analysis showed hydrodynamic diameters of 99.3 ± 2.1 nm, 112.8 ± 3.4 nm, and 251.7 ± 4.6 nm for ZIF-8, PD@ZIF-8 and PD@ZIF-8/CS, respectively, with the zeta potential shifting from +12.6 to −3.9 mV after CS coating. The PD@ZIF-8 system achieved an outstanding drug-loading efficiency (91.34%) and exhibited pH-dependent release, reaching 92.5% release at pH 5.0 and 37 °C within 72 h, while the CS coating reduced the burst release by ∼35% and prolonged t0 from 18.4 h to 38.6 h, following the Korsmeyer–Peppas model (R2 = 0.991). The PD@ZIF-8/CS composite displayed potent antibacterial activity (inhibition zones: 24.6 ± 0.4 mm for S. aureus and 21.2 ± 0.3 mm for E. coli; MIC: 6.25 µg mL−1), demonstrating a synergistic effect of PD, ZIF-8 and CS. These findings indicate that PD@ZIF-8/CS is a strong and pH-sensitive nanoplatform that can selectively release the drug in the acidic microenvironment of infection sites, suggesting its potential utility as an antibacterial nanoplatform, pending further biological validation.
Abdul Ghaffar, Safdar Ali Amur, Quratulain Khuhro et al.· RSC Advances· 0 citations
A seeded growth strategy was developed to synthesize core-shell magnetic metal-organic framework (MOF) composites for magnetic hyperthermia (MHT) and MHT-triggered drug delivery. Cubic or spherical iron oxide nanoparticles, with nanocubes selected for their superior MHT performance, were coated with cetyltrimethylammonium bromide to enable aqueous ZIF-8 shell growth. Shell thickness strongly influenced heating efficiency under alternating magnetic fields (AMFs), with thinner shells and cubic cores yielding enhanced MHT performance. Doxorubicin (Doxo) was used as a model chemotherapeutic drug and loaded either by surface adsorption or via in-situ encapsulation during ZIF-8 growth, the latter achieving an exceptional loading efficiency of 98%. To ensure stability in physiological environments, an amphiphilic polymer coating was applied, improving dispersion while regulating shell degradation and drug release. Doxo-loaded composites exhibited efficient cellular uptake and lysosomal localization in glioblastoma and breast cancer cells. Confocal microscopy revealed that magnetic field exposure induced lysosomal permeabilization and redistribution of Doxo, indicating a potential lysosomal escape mechanism. Notably, enhanced cytotoxicity occurred only when AMFs were applied to Doxo-loaded composites, despite no measurable bulk temperature increase, suggesting localized MHT-induced intracellular damage. Overall, shell-tunable magnetic-MOF nanohybrids emerge as promising platforms for controlled, heat-free intracellular drug activation for targeted cancer therapy.
A. Panaite, A. Predeina, Aitor Alvarez Lorenzo et al.· Small· 0 citations
Despite advances in chemotherapy, the clinical efficacy of docetaxel (Doc) in breast cancer treatment is limited by systemic toxicity and poor delivery efficiency. In this study, electrospun poly(lactic acid) (PLA):gelatin (Gel) core-shell nanofibers were developed as a dual drug delivery system for the co-delivery of Doc and heparin (HP). The core-shell architecture enabled the spatial compartmentalization of hydrophobic Doc within the PLA core and hydrophilic HP within the gelatin shell, allowing independent and controlled release profiles. Nanofibers containing 2, 3, and 5 wt% Doc in the core and corresponding amounts of HP in the shell were successfully fabricated. In vitro release studies performed at pH 3.0, 5.5, and 7.4 (37 °C) demonstrated a compartment-dependent release behavior, where HP exhibited rapid release (̴ 10 h), while Doc showed sustained release (̴ 80 h). These results indicate that the core-shell structure effectively regulates drug diffusion and enables distinct release kinetics for each therapeutic agent. Increased drug loading resulted in higher cumulative release for both agents. Cytotoxicity studies on MCF-7 breast cancer cells revealed that dual drug-loaded nanofibers (5 wt%, 2 mg) significantly reduced cell viability after 72 h, indicating enhanced in vitro antiproliferative activity. While Doc alone exhibited limited cytotoxic effect and HP showed negligible direct cytotoxicity, their combined delivery within the core-shell nanofiber system resulted in a markedly enhanced antiproliferative response. This enhanced effect indicates improved antiproliferative activity associated with dual-drug delivery through the core-shell nanofiber system. Overall, the developed PLA:Gel core-shell nanofibers represent a promising biomaterial-based platform for dual drug delivery of hydrophobic and hydrophilic agents, offering controlled release and promising in vitro antiproliferative activity.
S. C. Suner, A. Oral, Ayça Mehmetoğlu Al et al.· European journal of pharmace...· 0 citations
Cross-linked polysaccharide-based nanofibers were successfully fabricated as controlled drug delivery systems for 5-fluorouracil (5-FU) and caffeine (Caf). Characterization by SEM, FTIR, ^1H NMR, XRD, and elemental analysis confirmed uniform fiber morphology (180-220 nm), efficient drug incorporation, molecular-level drug-polymer interactions, and predominantly amorphous drug dispersion. In vitro release studies demonstrated sustained drug release over 72 h, with Caf showing pH-independent release and 5-FU exhibiting pH-responsive behavior. Kinetic analysis revealed diffusion-controlled Higuchi release under acidic conditions and first-order release under basic conditions (n < 0.5, Korsmeyer-Peppas), with no burst release observed. MTT assay on HepG2 cells indicated enhanced cytotoxicity of 5-FU-loaded nanofibers (CC50 = 7.5 ± 0.2 μM) compared to free 5-FU (CC50 = 14.5 ± 0.4 μM), while blank nanofibers were non-toxic. These results demonstrate that the developed nanofibers are a robust, tunable, and pH-responsive platform for site-specific chemotherapeutic delivery, warranting further in vivo evaluation and mechanistic studies.
Anam Shabbir, Sana Afzal, M. S. Iqbal· Journal of Biomaterials Scie...· 0 citations
A biocompatible, injectable, and self-healing hydrogel was constructed via electrostatic self-assembly of anionic pectin (PEC) and cationic quaternized guar gum (QGG). The optimized PEC/QGG hydrogel (QPE5, 1:3.5 ratio) exhibited rapid gelation (1.5 min), high yield (95.7%), shear-thinning behavior (viscosity decrease from 430 to 1.7 Pa·s), and excellent self-healing with ∼90% recovery of compressive strength. Zeta potential analysis confirmed charge neutralization (+2.9 mV for QPE5), indicating strong electrostatic interactions. The hydrogel displayed pH- and enzyme-responsive degradation, with accelerated disintegration under acidic (pH 5.5) and pectinase-rich conditions. 5-Fluorouracil (5-FU) was loaded with encapsulation efficiency of ∼72% and loading efficiency of ∼15% for QPE3 formulation. Drug release was adequately described by kinetic models, with the best-fitting model depending on the release conditions. The hydrogel demonstrated excellent cytocompatibility (>80% cell viability) and hemocompatibility (<2% hemolysis), while enabling selective inhibition of CT-26 colon carcinoma cells (viability reduced to ∼40% with enzyme-triggered release). This PEC/QGG platform integrates injectability, self-healing, and colon-specific degradability, offering a promising approach for localized colorectal cancer therapy.
A. Rahmatpour, Melika Emami Kian, Parvaneh Soleimani· Biomacromolecules· 0 citations
In vivo studies using an infected wound model demonstrated that the CG/BZC sponge significantly promotes tissue regeneration and accelerates wound healing, providing a promising and versatile approach for designing smart responsive dressings for advanced wound care.
Lanling Xiu, Zhitong Xu, Yueguang Fang et al.· Journal of materials chemist...· 0 citations
