Current Issue : October-December Volume : 2026 Issue Number : 4 Articles : 5 Articles
Introduction: Ursolic acid (UA), the antimalarial triterpenic mixture 8TTE (containing C-27 feruloyl and coumaroyl esters of ursane and oleane skeletons), and the semi-synthetic antitrypanosomal derivative ursolic acid Ophenyl propionate (UAOPP) exhibit high lipophilicity, which may limit their oral bioavailability. This study aimed to develop lipid nanocapsules (LNCs) to improve the solubility, intestinal permeability, and antiparasitic activity of these triterpenic compounds for potential oral delivery. Methods: LNCs formulations containing UA, 8TTE, and UAOPP were prepared and evaluated. A sensitive UPLC–MS method was developed and validated for selected triterpenes quantification during transport studies across Caco-2 cell monolayers [limit of detection (LOD): 2 nM; limit of quantification (LOQ): 25 nM]. Cytotoxicity and permeability studies were conducted on Caco-2 cells to assess formulation safety and intestinal transport. In vitro antiparasitic activity of free and formulated compounds was evaluated against Plasmodium falciparum and Trypanosoma brucei brucei (Tbb). Results and discussion: The formulations were non-toxic to Caco-2 cells at concentrations up to 2 mg/mL. Permeability studies demonstrated enhanced transport for the formulated triterpenic esters, with permeability increases of up to 2.68-fold, shifting their classification from poorly absorbed to moderately absorbed compounds in humans [apparent permeability coefficient (Papp) > 1 × 10–6 cm/s]. Free UA showed the highest Papp value (4.95 × 10–6 cm/s ± 1.29 × 10–7), but caused epithelial integrity disruption after 2 h of incubation and during the following 48 h, whereas formulated UA induced minimal integrity loss at the same concentration. In antiparasitic assays, blank LNCs exhibited maximum non-toxic concentrations of 165 μg/mL against P. falciparum and 65 μg/mL against Tbb. At these maximum concentrations, formulated UA and 8TTE showed enhanced antiplasmodial activity; however, blank LNCs produced comparable effects. In contrast, UAOPP-loaded LNCs showed significantly improved antitrypanosomal activity by approximately 20% at 2.15 μM (cell viability: 38.20% ± 5.41) compared with free UAOPP (20.38% ± 8.80). These findings suggest that LNCs represent promising oral delivery systems for lipophilic triterpenes. Further in vivo pharmacokinetic and efficacy studies are needed to confirm their therapeutic potential....
Soft polymeric nanocarriers provide programmable platforms for precision drug delivery, yet their rational design remains constrained by complex relationships among polymer chemistry, soft-matter properties, formulation, and biological performance. Bioorthogonal chemistry offers a modular route to functionalize these systems under physiologically compatible conditions, enabling selective ligand installation, responsive crosslinking, and therapeutic activation. Artificial intelligence and machine learning can complement these capabilities by predicting polymer behavior, optimizing reaction and formulation parameters, and linking physicochemical descriptors with biological outcomes. This Mini Review discusses the convergence of AI/ML and bioorthogonal chemistry for engineering smart soft polymeric nanocarriers, highlights opportunities in closedloop discovery and personalized nanomedicine, and examines translational barriers involving datasets, interpretability, reproducibility, manufacturability, and regulation....
Background: Non-small cell lung cancer (NSCLC), a malignant tumor with high global incidence and mortality rates, urgently requires more effective targeted drug delivery systems for its treatment. As an EGFR tyrosine kinase inhibitor, gefitinib has its clinical efficacy limited by poor solubility and low bioavailability. This study aimed to develop a gefitinib–salicylic acid salt (Gef-Sa) and its nano-formulation (Gef-Sa-NPs) via a combined strategy of crystal engineering and nanotechnology to improve its pharmaceutical properties. Methods: Gef-Sa was prepared using a suspension method, and its salt formation and thermal stability were predicted by the ΔpKa rule and confirmed by various solidstate characterization techniques, including single crystal/powder X-ray diffraction, thermal analysis, and infrared spectroscopy. Gef-Sa-NPs were prepared via an ultrasoundassisted anti-solvent precipitation method. Their performance was evaluated through in vitro dissolution tests, pharmacokinetic studies, and in vitro antitumor experiments. Results: Gef-Sa-NPs with a particle size of 31 nm (PDI = 0.15) were successfully prepared. In vitro dissolution tests demonstrated that the nano-formulation exhibited a significantly higher dissolution rate in pH 1.2, pH 4.5, pH 6.8 and pure water when compared with the raw drug (p < 0.01). Pharmacokinetic studies revealed that Gef-Sa and Gef-Sa-NPs increased the oral bioavailability in rats to 1.5-fold and 1.9-fold that of the raw drug, respectively. In vitro antitumor experiments confirmed that the Gef-Sa-NPs increased the inhibition rate against A549 cells compared with the Gef. Conclusions: This study innovatively combines salt formation and nanonization technologies to systematically address the key issue of the poor solubility of Gef. The resulting nano-formulation demonstrates excellent dissolution characteristics, pharmacokinetic behavior, and antitumor efficacy. This strategy not only provides a novel drug delivery system with translational potential for NSCLC treatment but also offers a paradigm for the formulation design of poorly soluble drugs. Subsequent research will focus on scaling up production and evaluating preclinical safety....
Background/Objectives: Supramolecular hydrogels formed by low-molecular-weight gelators present a chemically heterogeneous transport environment whose molecularscale dynamics remain poorly understood. This study aimed to investigate how drug physicochemistry governs transport within a liquid-crystalline C18ADPA hydrogel at the molecular scale. Methods: Pulsed-field gradient NMR spectroscopy was used to measure self-diffusion coefficients of five model drugs (5-fluorouracil, acetylcholine, paracetamol, prednisolone, and amphotericin B) spanning a broad range of size, polarity, and charge state, in both free solution and the hydrogel matrix at pH 5.37. Results: Observed drug diffusion coefficients deviated substantially from classical obstruction theory predictions, demonstrating that transport is governed by host–guest chemical affinity rather than molecular size. The three water-soluble drugs exhibited bimodal diffusion, with relative amplitudes providing a direct estimate of bound and free drug fractions. Prednisolone co-diffused with the gelator scaffold, consistent with hydrophobic bilayer partitioning, while amphotericin B diffused at rates consistent with the structured interfacial water layer. The gel pH (5.37) emerged as an active determinant of transport: drug charge states at this pH from permanent cation (acetylcholine) to near-zwitterion (amphotericin B) correlated directly with the observed transport behavior. The near-zwitterionic character of amphotericin B at pH 5.37, arising from its carboxyl pKa (~5.5), suggests a previously unreported electrostatic interfacial trapping mechanism. Conclusions: The liquid-crystalline bilayer architecture creates chemically distinct microdomains that selectively recruit drugs based on hydrophobicity, hydrogen-bonding capacity, and pH-dependent charge state, providing a molecular-scale framework for rational formulation design in supramolecular drug delivery....
With the declining success rate of new drug development, lifecycle management strategies have become increasingly important. However, approximately 25–40% of approved drugs remain limited to a single indication. In this study, we compared drugs that obtained multiple indications with those confined to a single indication, aiming to identify factors associated with the acquisition of multiple indications. We identified anticancer drugs initially approved by US Food and Drug administration (FDA) between 2015 and 2020. This retrospective observational study includes 48 anticancer drugs for solid tumors. For each drug, data were collected on approved indications, sponsoring company characteristics, and clinical efficacy outcomes, including objective response rate (ORR) and progression-free survival (PFS). The drugs were categorized based on the number of approved indications, and comparative analyses were conducted. No clear association was observed between multiple indication acquisition and factors such as mechanism of action (MoA) or company size at the initial approval. Since additional indications may be obtained through various approaches—including expansion to new tumor types or different lines of therapy—no consistent relationship was observed between specific strategies and the acquisition of multiple indications. In contrast, drugs demonstrating higher clinical efficacy and those initially approved for non-rare cancers were more likely to achieve multiple indications. The factors associated with additional indications varied depending on the approach, and only a limited set of factors consistently correlated with multiple indication acquisition. Notably, clinical efficacy and the tumor type at initial approval appeared to be associated with acquisition of multiple indications. These findings provide important insights into research and development strategies and may inform decision-making in pharmaceutical lifecycle management....
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