Search Results (282)

Background/Objectives: Peritoneal metastases (PMs) remain difficult to treat because the peritoneum–plasma barrier limits drug penetration from the systemic circulation. Intraperitoneal chemotherapy (IPC), particularly repeated intraperitoneal (IP) administration via implantable ports, can achieve high local drug exposure with prolonged retention. This review summarizes the pharmacological rationale, clinical evidence, and future directions of catheter-based IPC, with emphasis on combined IP and systemic chemotherapy for ovarian, gastric, and pancreatic cancers. Methods: We narratively reviewed prospective clinical trials and key retrospective studies evaluating IPC and compared repeated catheter-based IPC with hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). Efficacy, safety, practice considerations, and opportunities for ascites-based monitoring were examined. Results: In ovarian cancer, several randomized trials demonstrated improved progression-free survival (PFS), and in selected trials, improved overall survival (OS) was demonstrated using IP plus intravenous (IV) therapy, although in the latter trials, toxicity and catheter-related complications limited treatment completion. A phase III Intraperitoneal Therapy for Ovarian Cancer with Carboplatin (iPocc) trial further showed significantly prolonged PFS with IP carboplatin and weekly paclitaxel, with non-catheter-related toxicity comparable to that of IV therapy. In gastric and pancreatic cancer, phase II studies reported symptomatic control, cytologic conversion, and higher rates of conversion surgery in selected patients, although confirmatory phase III data are limited. Device complications, including infection, obstruction, and leakage, occurred, but were manageable. Conclusions: Repeated catheter-based IPC is a feasible approach that enhances intraperitoneal drug delivery and complements IV chemotherapy. Future priorities include randomized trials, pharmacokinetic optimization, and biomarker-guided patient selection, supported by serial ascites assessment to refine indications and improve outcomes. Full article

Polymeric micelles have the potential to improve the efficacy and safety of drug delivery by improving drug solubility, enhancing bioaccumulation and reducing off-target toxicity. Despite excellent safety profiles, a major limitation with polymeric micelles is their inability to rapidly release their payload once they have reached their target, leading to the inadequate delivery of therapeutic doses. To address this limitation, we have developed a novel strategy to impart pH-responsiveness in non-responsive micelles through the co-encapsulation of oligoelectrolytes with drugs. Herein, we investigate the influence of copolymer composition and drug identity in combination with oligoelectrolyte—oligo(2-vinyl pyridine) (OVP)—loading on pH-triggered drug release from micelles and their cytotoxicity. A library of OVP-loaded micelles was prepared using conventional and well-established non-responsive block copolymers. Dynamic light scattering (DLS) was used to monitor the changes in the micelles as a function of pH. Regardless of the copolymer composition, an abrupt decrease in the hydrodynamic diameter (D_h) was observed as the pH was reduced due to OVP expulsion from the core, which was also confirmed by release studies. In general, co-encapsulation of OVP and model drugs (doxorubicin (DOX), gossypol (GP), paclitaxel (PX), and 7-ethyl-10-hydroxycamptothecin (SN38)) in the micelles provided good to excellent encapsulation efficiency percentage (EE%) values. In vitro studies revealed the pH triggered release of drugs from the OVP-loaded micelles regardless of the drug identity, which increased as the OVP loading increased. This general behaviour was observed in all cases, largely independent of the copolymer composition, albeit with subtle differences in the release profile for different drugs. Compared to their blank counterparts, the drug-loaded micelles displayed a slight increase in cytotoxicity against a panel of cancer cell lines, in a dose dependent manner. However, drug- and OVP-loaded micelles displayed a significant increase in cytotoxicity (up to 8-fold increase) that was independent of the copolymer composition. These results demonstrate the versatility of the oligoelectrolyte-mediated approach to furnish non-responsive micelles with a pH-trigger that allows the rapid release of drugs, regardless of the micelle composition or the drug identity. Full article

Hepatocellular carcinoma (HCC) remains one of the most common malignancies worldwide and a leading cause of cancer-related mortality. Current treatment options for advanced or unresectable HCC have limited efficacy and are often associated with systemic toxicity. In this study, a multifunctional, thermosensitive hydrogel-based delivery system was developed to enhance localized treatment of HCC. This system incorporates rhenium-188 sulfur colloid (¹⁸⁸Re-colloid), a β-emitting radiotherapeutic agent, and paclitaxel (PTX)-loaded micelles within a biodegradable PCL-PEG-PCL hydrogel matrix. The formulation enables in situ gelation at physiological temperatures, providing sustained release and prolonged retention of therapeutic agents at the tumor site. Physicochemical characterization confirmed the structural integrity and injectability of the formulations, while in vivo biodistribution studies in a murine hepatic tumor model demonstrated enhanced intratumoral accumulation and reduced systemic dispersion. The combined chemo-radiotherapeutic platform showed potential for improved therapeutic efficacy through synergistic action, offering a promising minimally invasive strategy for treating unresectable hepatocellular carcinoma. Full article

This study reports the development of paclitaxel (PTX)-loaded human serum albumin (HSA) nanoparticles (NPs), surface-decorated with trastuzumab (TMAB), with potential applicability in HER2-oriented delivery. The NPs were obtained via thermally driven self-assembly followed by non-covalent antibody adsorption and they were characterized using Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and ζ-potential analysis. The drug association efficiency (%DAE), defined exclusively for PTX, was high for both HSA-PTX and HSA-PTX-TMAB NPs (96.4% and 98.2% w/w, respectively), with loading capacities (%LC) of 8.9% and 7.4%, respectively. TMAB decoration led to a modest increase in mean diameter and a reduction in surface charge, consistent with successful surface modification. Both formulations exhibited rapid early-phase PTX release followed by an apparent stabilization phase, with distinct kinetic behavior between HSA–PTX and HSA–PTX–TMAB NPs. Cytotoxicity in A549 cells after 18 h of exposure showed modest, non-differential effects consistent with controlled release and short-term assessment of non-specific toxicity. Overall, this thermally assembled albumin-based system provides a promising foundation for further evaluation of HER2-oriented PTX delivery. Full article

Potassium (K⁺) channel blockers are promising anticancer agents but suffer from off-target toxicities. We designed cross-linked poly-2-Hydroxyethyl methacrylate (HEMA)–pectin nanogels (HPN) to deliver two model blockers—dofetilide (Dof) and azimilide (Azi)—and evaluated their physicochemical properties, release behavior, and in vitro anticancer activity. HPN was synthesized by surfactant-assisted aqueous nanogel polymerization and comprehensively characterized (FTIR, DLS, TEM/SEM, XRD, BET). The particles were monodispersed with a mean diameter ~230 nm, compatible with tumor accumulation via the Enhanced Permeability and Retention (EPR) effect, and exhibited a microporous matrix suitable for controlled release. Drug loading was higher for Dof than for Azi, with DL% values of 82.30 ± 3.1% and 17.84 ± 2.9%, respectively. Release kinetics diverged: Azi-HPN followed primarily first-order diffusion with a rapid burst, whereas Dof-HPN showed mixed zero/first-order behavior. Cytotoxicity was assessed in A549 lung cancer and BEAS-2B bronchial epithelial cells. Both free and nano-formulated blockers were selectively toxic to A549 with minimal effects on BEAS-2B. Notably, a hormesis-like pattern (low-dose stimulation/high-dose inhibition in MTT) was evident for free Dof and Azi; encapsulation attenuated this effect for Dof but not for Azi. Co-administration with paclitaxel (Ptx) potentiated Dof-HPN cytotoxicity in A549 but did not enhance Azi-HPN, suggesting mechanism-dependent drug-drug interactions. Overall, HPN provides a biocompatible platform that improves K⁺ blocker delivery. Full article

Background/Objectives: Polysorbate 80 (PS80), a complex surfactant mixture, is widely recognized for its ability to enhance drug permeation across the blood–brain barrier (BBB). While this effect is generally attributed to the combined actions of its components, the specific contribution and potential selectivity of individual minor components remain poorly understood. This study therefore aimed to isolate and compare the primary minor components of PS80 to determine whether they uniformly enhance BBB permeation or exhibit drug-specific functions. Methods: In this research, four primary minor components of PS80—polyoxyethylene sorbitan monooleate (PSM), polyoxyethylene isosorbide monooleate (PIM), polyoxyethylene sorbitan dioleate (PSD), and a polyethylene glycol/polyoxyethylene sorbitan/polyoxyethylene isosorbide mixture (PEG/PS/PI mixture)—were isolated using preparative liquid-phase chromatography. Drug-loaded formulations were then prepared using the solvent evaporation method incorporating five model drugs: 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR, MW = 1013.39 Da), donepezil (MW = 379.49 Da), nimodipine (MW = 418.44 Da), chlorogenic acid (MW = 354.31 Da), and paclitaxel (MW = 853.92 Da). The permeability of these formulations across the BBB was evaluated in BALB/c mice after intravenous administration. Brain distribution of the lipophilic dye DiR was assessed using fluorescence imaging, whereas brain homogenate concentrations of therapeutic drugs were quantified by UPLC-MS/MS. Results: Results revealed that the enhancement of brain delivery was dependent on both the specific minor component and the drug. The PEG/PS/PI mixture specially enhanced the brain homogenate concentration of donepezil to 11.8 ± 1.2 ng/mL, representing a 6.9-fold enhancement, while PIM micelles increased the delivery of DiR, donepezil, and nimodipine. In contrast, PSM and PSD micelles improved transport of only DiR and donepezil. The broad performance of PIM suggests a more flexible formulation—a hypothesis that warrants further validation. Conversely, none of the different minor components enhanced the delivery of chlorogenic acid or paclitaxel, underscoring the critical role of specific drug–component interactions. Conclusions: This component-resolved insight challenges the conventional perception of PS80 and provides a rational framework for engineering precision brain-targeted delivery systems by selecting functional minor components. Full article

Selenium nanoparticles (SeNPs) have emerged as promising metal-based nanoparticles for drug delivery due to their unique physicochemical properties, intrinsic bioactivity, and biocompatibility. SeNPs offer a lower toxicity, higher bioavailability, and flexibility to be customized for surface chemistry compared to traditional selenium compounds. Advances in synthetic strategies, including chemical reduction, green biosynthesis, and surface functionalization with polymers, peptides, or ligands, have improved their stability, targeting capability, and circulation time. SeNP-based systems have demonstrated unique anticancer, antimicrobial, and anti-inflammatory activities, as they can function as drug carriers and active therapeutic agents. The surface of SeNPs has been functionalized with ligands such as Arginylglycylaspartic acid (RGD) peptides, hyaluronic acid, or chitosan to enhance their receptor-mediated targeting abilities in tumor tissues. In addition, SeNPs have shown a synergistic effect in the presence of drugs such as doxorubicin and paclitaxel. Even though SeNPs have demonstrated significant potential in pre-clinical investigations, their use in clinical studies has not been expanded due to several limiting challenges, including large-scale production, long-term safety, pharmacokinetic properties, and regulations required for FDA approval. Continued research into optimizing formulation strategies and expanding in vivo validation will be critical to translating SeNP-based drug delivery systems into clinical applications. In this review, we focus on the methods for synthesizing SeNPs, their physicochemical properties, the structure of ligands attached to SeNPs for drug delivery applications, and the specific biological targets of functionalized SeNPs. Full article

Background: Paclitaxel (PTX), a taxane chemotherapy drug, is widely regarded as one of the most potent and clinically effective treatments for advanced and resistant cancers. However, paclitaxel’s poor bioavailability is attributed to its unfavorable physicochemical properties, including low solubility and permeability. Nanosizing and multidrug combination strategies have emerged as key approaches to enhance the formulation of such compounds. Pterostilbene (PTE), a polyphenolic compound, possesses extensive anti-cancer properties and favorable hydrogen bond formation sites. In this study, PTE was employed to co-assemble with PTX to improve its physicochemical properties and enhance therapeutic efficacy. Methods: Paclitaxel-pterostilbene nanoparticles (PTX-PTE NPs) were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Results: PTX-PTE nanoparticles significantly improved the water solubility (7fold increase) and cytotoxicity of paclitaxel in tumor cells. The enhanced antitumor efficacy was achieved through P-gp and CDK1 protein downregulation, increased drug accumulation, and cell cycle inhibition. Conclusions: These improvements are attributed to the nanoparticles’ amorphous structure and nanoscale properties. In addition, the combined use of PTX and PTE significantly enhanced the cytotoxicity against human non-small cell lung cancer A549 cells. PTX-PTE nanoparticles show promise for improving drug delivery and overcoming multidrug resistance in A549 cells. Full article

Background/Objective: Cannabidiol (CBD) has gained increasing interest due to its multifaceted anticancer properties and favourable safety profile. Glioblastoma multiforme (GBM), a highly aggressive brain tumour with limited treatment options, represents a compelling target for CBD-based therapies. In this study, we report the rational design of two distinct formulations of lipid nanocapsules (LNCs) co-encapsulating CBD and a chemotherapeutic agent, tailored for intracranial and systemic administration. Methods: The cytotoxicity of various CBD–chemotherapeutic combinations, including temozolomide, carmustine, doxorubicin, and paclitaxel (PTX), were screened in vitro in U-87 MG and U-373 MG human GBM cell lines and analyzed for chemical compatibility. Moreover, the efficacy and the anti-migratory effect of the selected combination was further assessed in ovo and in vitro, respectively. Lastly, two LNC formulations coloaded with the selected combination were prepared in two different sizes via the phase inversion temperature method. Results: First, CBD in solution exhibited potent cytotoxicity and significantly inhibited cell migration in both GBM cell lines. Among the CBD–chemotherapeutic combinations tested, only CBD + PTX demonstrated both additive/synergistic interaction and favourable chemical compatibility. Second, this enhanced effect was confirmed in ovo. Third, the CBD + PTX combination also exhibited anti-migratory effect. Finally, two co-loaded LNC formulations—51.2 ± 0.9 nm and 25.9 ± 0.3 nm in size—were developed for intracranial and systemic delivery, respectively. Both formulations exhibited high monodispersity, a slightly negative ζ-potential, and consistently maintained a 7.5:1 CBD:PTX mass encapsulation ratio across both particle sizes. Conclusions: CBD + PTX co-loaded LNCs represent a promising and versatile nanomedicine platform for GBM therapy. Full article

Implantable drug delivery devices may enhance therapeutic efficacy by allowing localized drug release, and they may overcome the drawbacks of conventional systemic treatment. Electrospun nanofibers are promising drug delivery systems due to their high surface-to-volume ratio, porosity, and easy drug encapsulation. However, controlled and sustained drug release is required to improve therapeutic efficacy and reduce toxicity. Also, the ability to tailor the release drug dose would be a useful tool for providing an optimal and individualized approach for the treatment. Therefore, the aim of the study was to analyze the possibility to tailor the release of paclitaxel (PTX) from poly(D,L-lactide-co-glycolide) (PDLGA) electrospun nonwovens by modifying the comonomer molar ratio. For this purpose, three kinds of polymers were compared with lactidyl-to-glycolidyl comonomer ratios of 86:14, 70:30, and 48:52. Also, nonwovens obtained from a blend of PDLGA and PVA were used to analyze the effect of the addition of the hydrophilic polymer on degradation and, thus, the release rate. The comprehensive analysis of the developed nonwovens was conducted through an evaluation of the morphology, in vitro degradation, and drug release process, as well as cytotoxicity. It has been observed that all kinds of the developed PDLGA nonwovens provide an extended-release profile but with different release rates, which depend on the comonomer unit ratio and molar mass of the copolymer. Moreover, the increase in hydrophilicity caused by PVA sufficiently accelerates PTX release. The biological activity of released PTX was confirmed under in vitro and in vivo conditions against 4T1 mouse mammary carcinoma. The results of the study enabled us to gain insight into the influence of polymer choice on PTX release from PDLGA ES implants, which may be helpful in their easier translation into the clinic and for better adjustment of the PTX dose for individual treatment. Full article

Background: Paclitaxel (PTX) is an anti-neoplastic drug that inhibits not only melanoma cell proliferation but also migration and angiogenesis. ICOS-Fc is a recombinant molecule that triggers ICOS ligand (ICOSL) on tumor cells and cells of the tumor microenvironment and inhibits tumor growth, angiogenesis, and metastasis. This study investigated the effects of chitosan nanobubbles loaded with low doses of PTX and surface decorated with ICOS-Fc (ICOS-Fc-NB-PTX) in inhibiting in vitro and in vivo melanoma cell growth and invasiveness. Methods: Preparation and characterization of nanoformulations, as well as in vitro drug release studies, were carried out. Nanoformulations were studied both in vitro and in vivo. In melanoma cells, viability, migration, and invasion assays were analyzed. For the in vivo experiments, C57BL/6 Wild-type (WT) male mice were injected subcutaneously with D4M-3A cells, a murine melanoma cell line engineered to carry the BRAF^V600E mutation. After treatments, in vivo tumor growth, proliferation, and angiogenesis markers were studied. Results: In vitro tests showed the great ability of ICOS-Fc-NB-PTX to inhibit cell viability, migration, and invasion. These results were confirmed in vivo, where the tumors of mice treated with ICOS-Fc-NB-PTX displayed decreased growth accompanied by downregulation of the proliferation marker Ki-67 and reduced development of CD31⁺ blood vessels. Conclusions: In conclusion, the ICOS-Fc-NB-PTX formulation deserves to be further analyzed as a highly effective combination for melanoma, exerting multifaceted anti-tumor activities. Full article

Background/Objectives: This study aimed to further enhance the properties of paclitaxel (PTX) and honokiol (HNK) through encapsulation in planetary ball-milled nanoparticles (PBM NPs) and specific targeting of breast cancer (BrCa) cells via MUC1 targeting using an aptamer (S2.2) coating. Methods: Tissue microarray (TMA) analysis was utilized to measure MUC1 expression in stages 1, 2, 3, and 4 BrCa tissue samples. Pharmacokinetic simulations were performed to explore the potential advantages of using PTX and HNK in combination while targeting MUC1 for BrCa treatment. To investigate the efficacy of the PBM NPs for MUC1 targeting, we synthesized the aptamer-conjugated PTX and HNK PBM NPs (PTX-S2.2-PBM NPs, HNK-S2.2-PBM NPs) using N-hydroxysuccinimide (NHS) coupling. Dynamic light scattering (DLS), Fourier-transform infrared (FTIR), and high-performance liquid chromatography (HPLC) were utilized to characterize the NPs. MTT and live/dead cell assays were used to evaluate the cytotoxicity of the NPs. Results: TMA sample analysis confirmed the upregulation of MUC1 in BrCa tissues, which increased with the stage of BrCa. DLS analysis revealed that the PTX-S2.2 and HNK-S2.2 NPs have a desirable size (83.4 nm and 163 nm, respectively) and zeta potential (−9.74 mV and −7.16 mV, respectively), which are suitable for systemic circulation and improved therapeutic outcomes. FTIR and HPLC analysis suggest proper conjugation was achieved, and an encapsulation efficiency of PTXS2.2 and HNKS2.2 NPs at 77% and 84%, respectively, was achieved. Cell viability assays demonstrated that PTX-S2.2-PBM and HNK-S2.2-PBM NPs exhibit cytotoxicity comparable to or greater than free PTX and HNK, respectively. Conclusions: These findings support the belief that using PTX-S2.2 and HNK-S2.2 PBM NPs could be a promising treatment option for BrCa. Full article

Cancer poses a considerable challenge to global public health and stands as the second leading cause of mortality worldwide. Chemotherapy provides limited benefits for advanced-stage cancer, mainly due to high systemic toxicity and drug resistance. Optimal cancer treatment requires a sophisticated, multidisciplinary collaboration aimed at extending survival, enhancing quality of life, and reducing toxicity. Natural products present advantages, including a wide array of structural diversity, reduced toxicity, improved immune modulation, and the ability to act on multiple targets. Nanomedicine design shows promise in tumor treatment and diagnosis by improving efficacy and minimizing side effects. Due to the heterogeneity of tumors in genetics, metabolism, and microenvironment, natural product-based carrier-free drug delivery platforms have been actively investigated and demonstrated considerable potential for enhanced tumor treatment. “Triadic” strategies can simultaneously perform various functions on a carrier-free intelligent nanoplatform. These include combinational chemotherapy, photodynamic therapy (PDT) with bioimaging and chemotherapy, PDT combined with photothermal therapy (PTT) and chemotherapy, chemo-radio-theranostics, as well as gene therapy (GT) in conjunction with PTT and chemotherapy. This multifaceted approach enhances therapeutic efficacy, reduces multidrug resistance, and minimizes systemic toxicity. This review encompasses recent advancements in cancer therapy using carrier-free “triadic” nanomedicines based on natural products (between 2024 and 2025) and evaluates this evolving field, emphasizing the pivotal role of natural products—berberine, camptothecin, hypericin, erianin, curcumin, lactose, paclitaxel, gambogic acid, and glycyrrhizic acid—in drug delivery platforms. Furthermore, it addresses the challenges and bottlenecks encountered by carrier-free drug delivery platforms, offering valuable insights into their development trajectories. Full article

Reprogramming of macrophages into the inflammatory state (also known as M1) is currently considered as an effective way of eliminating cancer cells, but systemic deployment of this strategy is likely to induce dangerous autoimmune reactions. Consequently, converting immunosuppressive M2-type macrophages into M1 systemically is not a safe and effective therapeutic approach against cancer. Through cleavable covalent linking of curcumin to the chemotherapeutic agent Paclitaxel (Taxol), we have created a novel prodrug (STO-1) that, upon intravenous delivery, selectively reprograms tumor-associated microglia and macrophages (TAMs) and eliminates glioblastoma (GBM) without triggering autoimmunity. Demonstrating its therapeutic efficacy, prolonged treatment of six orthotopic GBM-bearing mice with STO-1 resulted in 67% long-term survival, with three surviving mice exhibiting complete tumor clearance and one displaying minimal residual disease, as confirmed by high-resolution ex vivo T2-weighted MRI 85 days after tumor inoculation. In contrast, the vehicle-treated mice displayed extensive intracranial tumors with edema and hemorrhage. Mechanistically, scRNA-seq analysis indicated induction of multiple M1-associated transcripts (ccrl2, cxcl9, ccr2, ccl5) consistent with robust TAMs reprogramming. In striking contrast to the M2⟶M1 reprogramming of TAMs, M1-type macrophages were suppressed in the spleens of STO-1-treated cancer-free mice. Therefore, STO-1 induces selective anti-tumor immunity and GBM elimination without triggering systemic autoimmune reactions. Full article

Cancer, a global health burden, is characterized by uncontrolled cell growth and metastasis, often resulting in debilitating treatments and mortality. While conventional therapeutic strategies have improved survival rates, they are limited by challenges such as off-target toxicity and drug resistance. With their design to enable targeted drug delivery, nanoparticles have presented a promising avenue to overcome these limitations. Protein-based nanoparticles, particularly those based on albumin, are notable for their biocompatibility, stability, and ease of modification. The approval of Abraxane, an albumin-based nanoparticle formulation of paclitaxel, for metastatic breast cancer marked a significant milestone. However, further approvals have been slow to materialize until the recent approval of Fyarro^® in 2021. This focused review highlights the potential of albumin-based nanoparticles, emphasizing their advantages, current state, and progress in clinical use as anticancer therapeutics. We also discuss challenges impeding new approvals and future directions for unlocking the full potential of this technology. Full article