Current Issue : July-September Volume : 2026 Issue Number : 3 Articles : 5 Articles
Objectives: This study developed pH/enzyme-sensitive polymeric HA-AAN-DOX (HAD) micelles to resolve the limited targeting specificity of chemotherapy drugs. Methods: Hyaluronic acid (HA) and the chemotherapeutic agent doxorubicin (DOX) were conjugated via a hydrazone linkage utilizing an Ala-Ala-ASP tripeptide (AAN) as the connecting moiety, which is sensitive to the legumain enzyme. DOX was delivered via HAD micelles, which were activated by both hyaluronidase and the legumain enzyme. Key findings: The results revealed the remarkable antitumor efficacy of these micelles both in vivo and in vitro. Compared with that of doxorubicin hydrochloride (DOX·HCl), the incidence of toxic side effects was significantly reduced with the HAD micelle treatment. As a result, micelles composed of hyaluronic acid and doxorubicin (HAD) offer a reliable and effective method for drug delivery, with the potential to optimize the therapeutic impact of chemotherapeutic agents on tumors by reducing unintended side effects. Conclusions: Micelles composed of hyaluronic acid and doxorubicin (HAD) offer a reliable and effective method for drug delivery, with the potential to optimize the therapeutic impact of chemotherapeutic agents on tumors by reducing unintended side effects....
Transdermal drug delivery (TDD) provides a non-invasive approach for sustained drug release. However, traditional models present limitations in capturing the dynamic interactions between drugs, skin and the environmental factors over time. The incorporation of time as a critical dimension alongside threedimensional (3D) structures in four-dimensional (4D) modelling offers a promising solution by simulating the temporal evolution of drug diffusion and skin responses. In this review, 4D modelling refers to the computational and material-based systems that incorporate time-dependent changes whereas 4D bioprinting specifically involves fabrication of dynamic, stimuli-responsive skin constructs. Together, these approaches create temporally adaptive models which are ideal for simulating drug permeation and skin behaviour. This review will explore the potential application of 4D modelling in TDD, primarily focusing on and emphasising its capacity to predict drug permeation, release kinetics and skin interactions in response to variables such as hydration, temperature and mechanical impact. 4D bioprinting provides a more accurate depiction of real-world scenarios, enabling researchers to optimise drug formulations whilst minimising reliance on empirical testing. Despite challenges associated with cost and complexity, 4D modelling presents considerable opportunities, particularly in the advancement of personalised medicine. The integration of artificial intelligence could further enhance these models, resulting in more accurate predictions. By addressing both spatial and temporal dimensions, 4D constructs will continue to evolve and have the potential to transform TDD; particularly in the context of individualised treatment where dynamic patient-specific variables can be integrated to develop more effective and tailored treatments....
Background/Objectives: Although the Calvert formula has been widely used to guide carboplatin dosing, it may yield inaccurate dose predictions in certain patient populations. We aimed to evaluate the adequacy of the conventional Calvert formula and to propose structural modifications to enhance dosing accuracy in breast cancer patients with preserved renal function (CrCL ≥ 55 mL/min). Methods: A systematic review and meta-analysis were conducted to integrate published pharmacokinetic models in patients with breast cancer. Two retrospective datasets (n = 154) were combined into a single analysis dataset and used to calculate carboplatin doses based on the conventional formulas using creatinine clearance (CrCL) or estimated glomerular filtration rate (eGFR), as well as a modified formula incorporating an additional constant (α). Performance was assessed by the proportion of subjects achieving target area under the curve (AUC) attainment (4–6 mg·min/mL), underexposure (<4 mg·min/mL), and overexposure (≥7 mg·min/mL). All AUC metrics were derived from model-based predictions rather than measured carboplatin concentrations, and no clinical toxicities or efficacy outcomes were used for validation. Results: Meta-analysis yielded fixed-effect parameter estimates (CL: 131.8 mL/min, V1: 15.39 L, K12: 0.002 min−1, and K21: 0.003 min−1) with a random effect model. The conventional CrCL-based formula yielded 66.0% target attainment, 22.1% underexposure, and 4.5% overexposure. Switching to eGFR improved attainment to 88.3%, reduced underexposure to 5.8%, and lowered overexposure to 0.65%. A modified formula with α = 1 further decreased underexposure (4.5%) while target attainment and overexposure remained unchanged. Conclusions: Replacing CrCL with Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-derived eGFR in the Calvert formula markedly improved dosing accuracy, while modest structural modification offered additional benefit. The incremental benefit of α = 1 should be considered hypothesis-generating and requires prospective validation with measured carboplatin concentrations and clinical outcomes before applying it in practice. These findings support adopting eGFR-based dosing in breast cancer and suggest the need for future clinical validation....
Background/Objectives: Microbe-derived extracellular vesicles (MEVs) provide a biocompatible, naturally derived platform for drug delivery. Methods: We encapsulated doxorubicin in Lactobacillus plantarum-derived EVs and evaluated their ability at delivering doxorubicin to colorectal cancer cells in vitro. Endocytosis inhibitors were used to investigate the mechanisms by which the MEVs entered the cells. Results: The MEVs maintained structural stability under physiological conditions. Cellular internalization of doxorubicin-loaded MEVs involve clathrin/caveolae-dependent endocytosis, and dynaminand clathrin-mediated pathways. Conclusions: These findings highlight the role of the microbe–cancer cell biointerface in mediating drug uptake and enabling intracellular delivery. The study supports the potential of MEVs as nanocarriers for anticancer drugs and provides mechanistic insights into the intracellular trafficking pathways that influence drug activity....
Background: Pantoprazole is a widely used proton pump inhibitor that is highly unstable under acidic conditions. This limits the performance of conventional formulations and typically requires enteric-coated dosage forms or alternative modified-release approaches. This study reports the development of polymeric matrix mini-tablets designed to protect pantoprazole during gastric exposure and to enable pH-dependent release under intestinal conditions. The formulations combine Eudragit® S 100, a pH-dependent polymer, with HPMC, a hydrophilic matrix former that modulates drug release through hydration and swelling. Methods: Matrix mini-tablets were prepared by blending pantoprazole with selected excipients at optimised proportions and compressing the blends by direct compression using an eccentric tablet press. Powder blends and mini-tablets were characterised according to pharmacopoeial specifications. Analytical techniques—including High-Performance Liquid Chromatography (HPLC), Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Absorption Spectroscopy (FT-IR), Powder X-Ray Diffraction (PXRD), and Scanning Electron Microscopy (SEM)—were employed to evaluate drug content uniformity, thermal behaviour, and potential drug–excipient interactions. In vitro dissolution studies were performed under sequential pH conditions, and the release kinetics were analysed using mathematical models. Results: Dissolution testing identified formulations F2 and F6 as providing the most suitable gastro-resistant performance in the acidic stage, together with sustained release up to 24 h. Kinetic modelling supported formulation-dependent release mechanisms, and multivariate analysis (PCA) highlighted relationships between physico-mechanical attributes and drug-release behaviour. Conclusions: The proposed matrix system shows potential as a robust, coating-free platform for the modified delivery of acid-labile drugs using direct compression, simplifying manufacturing. These findings support the rational design of oral modified-release formulations based on polymeric matrices....
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