Search Results (341)

N-acetylcysteine (NAC) is a thiol-containing molecule with antioxidant, anti-inflammatory, antimicrobial, and cytoprotective properties that has increasingly been incorporated into hydrogel-based biomaterials. This systematic review evaluates the strategies used to integrate NAC into hydrogels and examines their effects on material properties, controlled release, biocompatibility, and therapeutic activity. The review was conducted according to the PRISMA guidelines using Scopus, PubMed, Web of Science, and SciFinder to identify English-language articles published between 2000 and 2025. Seventy-three studies met the eligibility criteria of this review. NAC has been employed as a physically loaded therapeutic agent, covalently conjugated polymer modifier, contributor to hydrogel crosslinking, metal-coordination ligand, and compound incorporated into nano- and microparticulate carriers dispersed in hydrogel. These approaches enable the modulation of gelation, swelling, adhesion, degradation, and drug-release kinetics. NAC-containing hydrogels have demonstrated robust antioxidant, antimicrobial, antibiofilm, anti-inflammatory, angiogenic, and tissue-regenerative properties in various in vitro and in vivo models, underscoring their potential for advanced biomaterial applications. Release profiles varied from rapid stimulus-responsive delivery to sustained release over several days, depending on the network architecture and the NAC–matrix interactions. However, comparisons among studies were limited by the heterogeneous formulations, release conditions, biological models, and outcome measures. Standardized physicochemical characterization, NAC stability assessment, dose–response evaluation, and rigorous preclinical validation are required to support the translation of NAC-based hydrogels into biomedical applications. We hope that this review will help scientists and innovation centers understand the potential of the NAC-containing hydrogel biomaterials discussed in this study, as well as the opportunities and demands for additional research in this field. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies due to limited responsiveness to chemotherapy and the high prevalence of oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. Co-delivery of cytotoxic agents and small interfering RNA (siRNA) is a potential combination strategy, but the two cargos have distinct physicochemical and intracellular-delivery requirements. Here, we developed a chitosan–polyethylene glycol (CP)-based polymeric nanoparticle platform for the cotreatment of paclitaxel (PTX) and small interfering RNA (siRNA) targeting KRAS G12D mutation. PTX was first modified to PTX-COOH through an ester-containing succinate linker and then covalently conjugated to the polymer backbone through amide bond formation, enabling stable nanoparticle formation and subsequent electrostatic complexation with siRNA. The CP-PTX-siRNA nanoparticles demonstrated efficient cellular uptake, while luciferase knockdown by CP-siRNA supported functional siRNA delivery by the CP carrier. In KRAS G12D–mutant pancreatic cancer cells, PTX- and KRAS-targeting siRNA-coloaded nanoparticles resulted in enhanced cytotoxicity compared to single-agent treatments and free drug combinations, with combination index values below 1 indicating calculated synergy under the tested in vitro conditions. Because KRAS knockdown and a non-targeting siRNA control were not assessed in PANC-1 cells, the enhanced cytotoxicity cannot be attributed specifically to KRAS silencing. Across multiple drug-to-siRNA ratios, nanoparticle formulations consistently improved treatment potency. Together, these results support CP-PTX-siRNA nanoparticles as a modular and biocompatible platform for combined PTX/siRNA delivery. This approach provides a versatile strategy for combining chemotherapeutic agents with RNA-based therapeutics in PDAC, supporting further development of these polymeric nanocarriers for combination cancer therapy. Full article

Background/Objectives: Superparamagnetic iron-oxide nanoparticles (SPIONs) bearing poly(methacrylate) brushes were synthesized via surface-initiated atom-transfer radical polymerization (SI-ATRP) as magnetically responsive nanoplatforms. Three brush architectures, poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(poly(ethylene glycol) methacrylate) with six ethylene-oxide units (PPEGMA6) and ten units (PPEGMA10), were grown from a dopamine-anchored initiator and covalently loaded with methotrexate (MTX). Methods: Physicochemical characterization confirmed successful polymer grafting, tunable hydrodynamic size (185–1320 nm before MTX conjugation and 427–694 nm after), retained superparamagnetic properties (22–69 emu g⁻¹), and high drug payloads, with PPEGMA6 achieving 131 µg mg⁻¹. MTX conjugation induced partial compaction of the polymer shell yet maintained ζ-potentials conducive to colloidal stability. Results: In vitro assays showed negligible toxicity toward primary human fibroblasts, whereas MTX-decorated formulations induced a pronounced concentration-dependent cytotoxic effect in MCF-7 breast cancer cells, reaching 69% loss of viability—significantly higher than free MTX. Structure–activity analysis attributes the superior performance of PPEGMA6-MTX to its balanced brush density, high payload, and favorable surface charge. Conclusions: These findings demonstrate that precise modulation of polymer brush architecture via SI-ATRP yields SPION-based nanocarriers that integrate MRI visibility and the potential for magnetic guidance and targeted chemotherapy. The PPEGMA6-MTX construct is highlighted as a promising platform for future preclinical investigations. Full article

Polymer-based nanoparticle systems have emerged as a versatile platform for advancing precision medicine by enabling controlled, targeted, and multifunctional drug delivery. This narrative review synthesizes recent progress in the design, functionalization, and clinical translation of polymer-based nanoparticles, with a focused scope on drug delivery, diagnostics, theranostics, nanosponges, and regenerative medicine. Specifically, it highlights three key insights: (i) surface engineering strategies, including ligand conjugation and stealth coatings, substantially enhance targeting specificity and reduce off-target toxicity; (ii) stimulus-responsive polymers enable spatiotemporally controlled drug release, improving therapeutic outcomes in complex disease microenvironments; and (iii) integration with artificial intelligence (AI) supports the rational design of personalized nanomedicines based on patient-specific molecular profiles. The innovative nature of this review lies in its comprehensive approach, which combines material design parameters with clinical outcomes and the barriers to implementation. Despite significant progress, serious challenges remain, including scalable and reproducible manufacturing, regulatory harmonization, and comprehensive long-term biosafety assessment. In the future, the priority should be to develop reliable manufacturing processes, a harmonized regulatory framework, and data-driven, clinically validated design methodologies. Overall, polymer-based nanoparticles are poised to redefine targeted therapy, but their clinical impact will depend on bridging the gap between laboratory innovation and scalable, safe, and personalized medical applications. Full article

Background/Objectives: Photodynamic therapy (PDT) relies on light activation of photosensitizers to generate reactive oxygen species for tumor ablation; however, limited tumor selectivity and systemic toxicity of free photosensitizers remain challenges. This study aimed to develop polymer-based nanotheranostics carrying tetraphenylporphyrin (TPPc) derivatives and to evaluate how linker structure impacts their performance. Methods: TPPc derivatives were covalently conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymers via either pH-sensitive hydrazone linkages (using aliphatic 5-hydroxy-2-pentanone or aromatic 1-(4-hydroxymethyl)phenyl)ethanone spacer) or stable amide bonds, forming amphiphilic polymer conjugates. The conjugates were characterized based on their physicochemical and in vitro and in vivo biological behavior. Results: Polymer conjugation reduced dark toxicity while preserving photodynamic activity. Linker structure influenced intracellular behavior and singlet oxygen production, with hydrazone systems showing faster activation-related responses under acidic conditions in vitro. All conjugates accumulated in tumors and induced significant tumor growth inhibition after irradiation at low doses (2.5 mg kg⁻¹ TPPc equivalent), while the amide-linked conjugate showed the strongest overall in vivo therapeutic effect, likely due to more favorable biodistribution and sustained delivery. Conclusions: The developed HPMA-based polymer–TPPc conjugates improve the therapeutic profile of photosensitizers by reducing toxicity and enabling effective PDT. These findings highlight the importance of linker design in balancing photosensitizer activation, circulation stability, and biodistribution, which together determine the overall therapeutic outcome. Full article

Background/Objective: In lung cancer treatment, increasing the concentration of antitumor drugs at the tumor site, enhancing efficacy, and reducing systemic toxicity are significant challenges. This study aims to develop an intelligent responsive polymer micelle system (GPDD) that achieves efficient accumulation and controlled release of drugs at lung tumor sites through targeted and pH-responsive design. Methods: The GPDD system is formed by the self-assembly of GE11-PEG-hyd-DOX conjugates and co-loads free DOX. This system utilizes the targeting effect of the GE11 peptide with the epidermal growth factor receptor (EGFR) to accumulate at the tumor site, while the hydrazone bond serves as a pH-responsive linker that breaks in the acidic tumor microenvironment, triggering drug release. Experiments employed CCK-8 cytotoxicity assays and tumor-bearing nude mouse models (strain not specified) for in vitro and in vivo evaluations. Results: In vitro experiments showed that GE11-modified GPDD effectively inhibited tumor cell growth. In tumor-bearing nude mouse experiments, GPDD demonstrated more significant tumor suppression effects and lower systemic toxicity compared to free DOX and unmodified PDD. Conclusions: The GPDD nanocarrier integrates targeting and pH responsiveness, improving antitumor efficacy and reducing side effects, with translational potential. The novelty of the study lies in its dual-functional design and co-loading strategy, providing new insights for tumor-targeted delivery systems. Full article

Biomaterials are engineered to interact with biological systems for therapeutic or diagnostic purposes. Among them, natural biomaterials offer important advantages over many synthetic polymers, including intrinsic biocompatibility, non-toxicity and biodegradability. Silk fibroin, a fibrous protein derived mainly from Bombyx mori cocoons, has re-emerged as a particularly versatile platform because it combines favourable mechanical, thermal, electrical and optical properties with aqueous processing and tuneable degradation. In this review, we first summarise the key structural, physicochemical and functional properties of regenerated silk fibroin, including its mechanical behaviour, thermal stability, dielectric and piezoelectric response, optical transparency and low autofluorescence. We then describe how extraction and regeneration protocols are used to produce defined material formats—fibres and nanofibrous mats, porous 3D scaffolds and hydrogels, sub-micron particles, thin films and microstructured devices—and outline major functionalisation strategies, ranging from physical blending and encapsulation to covalent chemistry, genetic engineering of recombinant silk variants, and enzyme-mediated conjugation approaches. Building on this foundation, we critically examine biomedical applications of silk fibroin with a particular emphasis on (i) hybrid silk–fluorophore systems for bioimaging and biosensing (nanodiamonds, quantum dots and organic dyes), (ii) optical fibre, wearable and edible sensors for health and food monitoring, (iii) wound dressings and wound-sensing platforms, and (iv) tissue engineering scaffolds and drug-delivery depots. Finally, we discuss current limitations, including process variability, the trade-offs introduced by blending and cross-linking, and the challenges posed by non-degradable inorganic fillers and clinical translation. Together, these perspectives highlight silk fibroin’s potential and constraints as a multifunctional biomaterial for next-generation biomedical devices and theranostic systems. Full article

Polymer–drug conjugates (PDCs) represent an advanced drug delivery strategy designed to address critical limitations of conventional therapeutics, including poor water solubility, rapid systemic clearance, and off-target toxicity. By covalently linking therapeutic agents to polymeric carriers through rationally designed linkers, PDCs enable improved pharmacokinetic profiles, enhanced stability, and controlled drug release. This review provides a comprehensive overview of the key design principles governing PDC systems, with a particular focus on the role of biofunctional polymers. Essential parameters for polymer selection, including biocompatibility, biodegradability, molecular weight, and functional group availability, are discussed in relation to their influence on drug loading, release kinetics, and biological performance. In addition, both natural and synthetic polymers are evaluated for their ability to improve solubility, modulate biodistribution, and reduce systemic toxicity. An overview of stimuli-responsive PDCs is provided, including pH-, redox-, and temperature-sensitive systems, which enable site-specific and spatiotemporally controlled drug release in response to pathological microenvironments. We emphasize the special role of bioactive polymers such as poly-lysine, hyaluronic acid, chitosan, and gelatin for their intrinsic biological activity, including receptor-mediated targeting, antimicrobial activity, and synergistic therapeutic effects. These properties support the development of dual-active conjugates with enhanced specificity and efficacy. Overall, this review underscores the transition of polymers from passive carriers to active therapeutic components and outlines current challenges and future perspectives for the clinical translation of next-generation PDCs. Full article

Background/Objectives: The formulation development of Isotretinoin (ISN) is limited by its solubility and stability issues. This study aimed to characterise the BCS class II drug ISN, particularly the possible different solid state and formulate amorphous solid dispersion aiming for a supersaturation state. Methods: ISN’s physical states are investigated in its raw form, quench-cooled form, physical mixture with the polymer and corresponding solid dispersion form. Quench-cooled ISN was prepared in situ using DSC. Carrier stabilisation of ISN was attempted using the solid dispersion technique. Hereby, the solid dispersion of drug-polymer PVPVA at a ratio of 1:3 was prepared using the solvent evaporation method. Solid dispersion, physical mixture and raw ISN were characterised for the saturated solubility. Physical characterisation of the samples was performed using DSC, ATR-FTIR and a light microscope. Results: Two polymorphs of ISN (forms I and II) were found in the raw ISN, with form II being thermodynamically more stable. ISN possesses strong crystallinity and resistance to amorphisation under the applied quench-cooling condition without the presence of a carrier system. The conjugated polyene structure in ISN contributes to the polymorphic transformation and isomerisation. The incorporation of PVPVA in the solid dispersion system successfully improved the water solubility (sixfold) of ISN despite a combination of crystalline and amorphous components being present in the system. Conclusions: ISN is a class II drug crystal molecule. Taking advantage of solubility and possibility in the polymorphic transformation of ISN in a binary system, we concluded that ISN could potentially be formulated into its corresponding crystalline solid dispersion form. Full article

Sexually transmitted infections, notably herpes simplex virus, remain significant global health concerns. Localized delivery systems that provide sustained antiviral activity at mucosal surfaces offer an attractive alternative to systemic therapies. In this study, we developed electrohydrodynamically deposited coatings utilizing a covalent acyclovir–poly (lactic-co-glycolic acid) (ACV–PLGA) conjugate for potential antiviral functionalization of medical devices. The ACV–PLGA prodrug was synthesized via drug-initiated ring-opening polymerization, yielding a copolymer characterized by FTIR, NMR, GPC, and DSC, with controlled drug loading and biodegradable properties. Systematic optimization of electrospinning and electrospraying parameters enabled the fabrication of both particulate and nanofibrous coatings on silicone ring models. Morphological analysis by SEM demonstrated that polymer concentration, solvent composition, and applied voltage critically governed coating architecture, ranging from microparticle layers to uniform bead-free fibers. In vitro studies revealed morphology-dependent degradation profiles and sustained release of ACV over 56 days. This integrated approach combining covalent prodrug synthesis with tunable electrohydrodynamic deposition offers a promising strategy for long-acting local antiviral prophylaxis via functionalized medical surfaces. Full article

L-asparaginase (L-ASNase) is a vital enzymatic drug widely used for treating acute lymphoblastic leukemia (ALL) and certain lymphomas. However, its clinical application is often limited by a short plasma half-life, pronounced immunogenicity, and systemic toxicities. To address these challenges, we recently developed conjugates of L-ASNase with cationic polymers, enhancing its cytostatic activity by increasing enzyme binding with cancer cells. The present study focuses on the development of liposomal formulations of E. coli L-asparaginase (EcA) and its conjugates with cationic polymers: the natural oligoamine spermine (spm) and a synthetic polyethylenimine–polyethyleneglycol (PEI-PEG) copolymer. This approach aims to improve enzyme encapsulation efficiency and stability within liposomes. Various formulations—including EcA conjugates with polycations incorporated into 100 nm and 400 nm phosphatidylcholine/cardiolipin (PC/CL, 80/20) anionic liposomes—were synthesized as a delivery system of high enzyme load. Fourier Transform Infrared (FTIR) spectroscopy confirmed successful enzyme association with liposomal carriers by identifying characteristic changes in the vibrational bands corresponding to both protein and lipid components. In vitro release studies demonstrated that encapsulating EcA formulations in liposomes more than doubled their half-release time (T_1/2), depending on the formulation. Cytotoxicity assays against Raji lymphoma cells revealed that liposomal formulations, particularly 100 nm EcA-spm liposomes, exhibited markedly superior anti-proliferative activity, reducing cell viability to 4.5%, compared to 35% for free EcA. Confocal Laser Scanning Microscopy (CLSM) provided clear visual and quantitative evidence that enhanced cellular internalization of the enzyme correlates directly with its cytostatic efficacy. Notably, formulations showing higher intracellular uptake produced greater cytotoxic effects, emphasizing that hydrolysis of asparagine inside cancer cells, rather than extracellularly, is critical for therapeutic success. Among all tested formulations, the EcA-spermine liposomal conjugate demonstrated the highest fluorescence intensity within cells providing enhanced cytotoxicity. These results strongly indicate that encapsulating cationically modified L-ASNase in liposomes is a highly promising strategy to improve targeted cellular delivery and prolonged enzymatic activity. This strategy holds significant potential for developing more effective and safer antileukemic therapies. Full article

Background/Objectives: Here, we report the design, synthesis, and in vitro biological evaluation of a novel stimuli-sensitive nanotherapeutics based on cisplatin analog, cis-[PtCl₂(NH₃)(2-(3-oxobutyl)pyridine)] (Pt-OBP), covalently linked to a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer via a pH-sensitive hydrazone bond. Methods: Two polymer–drug conjugates, P-Pt-A and P-Pt-B, were synthesized, differing in spacer length between the polymer chain and hydrazone bond, which in turn modulates their drug release kinetics. Results: The spacer based on hydrazone bond demonstrated satisfactory stability under blood-mimicking conditions while enabling selective release of the active drug intracellularly or even in the mildly acidic tumor microenvironment. Pt-OBP exhibits comparable or even superior cytostatic and cytotoxic activity to carboplatin across a panel of murine and human cancer cell lines, with the highest potency observed in FaDu cells representing human head and neck squamous cell carcinoma. Mechanistically, Pt-OBP induced significant phosphorylation of γ-H2AX and activation of caspase-3, indicating its ability to cause DNA damage with subsequent apoptosis induction. P-Pt-A retained moderate biological activity, whereas the slower-releasing P-Pt-B exhibited reduced potency in vitro, consistent with its drug release profile. Conclusions: Notably, free Pt-OBP induced rapid apoptotic cell death, surpassing carboplatin at early time points, and the polymeric conjugates achieved comparable pro-apoptotic activity after extended incubation, suggesting effective intracellular release of the active drug. Full article

Poly(carboxybetaine methacrylate)s (PCBMA) belongs to a class of zwitterionic polymers that offer promising alternatives to polyethylene glycol (PEG) in biomedical applications. This review highlights how the unique zwitterionic structure of PCBMA dictates its strong antifouling behavior, low immunogenicity, and sensitivity to environmental stimuli such as pH and ionic strength. These features make PCBMA promising for designing advanced systems suited for complex biological environments. This review describes PCBMA-based materials—ranging from hydrogels, nanogels, and surface coatings to drug carriers and protein conjugates—and critically evaluates their performance in drug delivery, tissue engineering, diagnostics, and implantable devices. Comparative studies demonstrated that PCBMA consistently outperformed other zwitterionic polymers and PEG in resisting protein adsorption, maintaining bioactivity of conjugated molecules, and ensuring long circulation times in vivo. Molecular dynamics simulations provide additional information into the hydration shells and conformational behaviors of PCBMA in aqueous dispersions. These insights underscore PCBMA’s broad potential as a promising high-performance material for next generation healthcare technologies. Full article

This study reports the synthesis and characterization of well-defined ionic graft conjugates acting as drug delivery systems, based on monomeric ionic units derived from choline methacrylate (TMAMA) biofunctionalized with the anions of ampicillin (AMP) or cloxacillin (CLX). Using the “grafting from” technique with multifunctional macroinitiators, the density of side chains was precisely defined, and the length of side chains was well-controlled during polymerization. The resulting ionic conjugates featured the regulated content of ionic fractions with drug anions reaching up to 55% and drug content up to 48–70% for AMP, 27–65% for CLX, and 47–79% for (CLX + AMP). The drug release behavior was evaluated under physiological conditions using a dialysis method. The ionic conjugates demonstrated release efficiencies of 70–93% for CLX (5–16 µg/mL), 69–98% for AMP (12–13 µg/mL) in single systems, and 61–73% for CLX + AMP (10–15 µg/mL) in dual systems. Additionally, polymer surface properties were evaluated via water contact angle measurements (WCA = 30–54°). In an aqueous solution, the polymer self-assemblies appeared to be nanosized particles (90–360 nm). The results demonstrate that the synthesized TMAMA-based graft copolymers act as effective ionic conjugates and dual drug systems, offering a promising platform for controlled and multi-drug delivery applications. Full article

Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral drug delivery system, KGM-CUR/PSM microspheres, to achieve precise drug release in CRC and enhance tumor-specific drug accumulation, which leverages high ROS levels in CRC and the β-mannanase overexpression in colorectal tissues. Methods: In this study, we synthesized a ROS-responsive prodrug polymer (PSM) by conjugating polyethylene glycol monomethyl ether (mPEG) and mesalazine (MSL) via a thioether bond. CUR was then encapsulated into PSM using thin-film hydration to form tumor microenvironment-responsive micelles (CUR/PSM). Subsequently, konjac glucomannan (KGM) was employed to fabricate KGM-CUR/PSM microspheres, enabling targeted delivery for colorectal cancer therapy. The ROS/enzyme dual-response properties were confirmed through in vitro drug release studies. Cytotoxicity, cellular uptake, and cell migration were assessed in SW480 cells. In vivo efficacy was evaluated in AOM/DSS-induced CRC mice, monitoring tumor growth, inflammatory markers (TNF-α, IL-1β, IL-6, MPO), and gut microbiota composition. Results: In vitro drug release studies demonstrated that KGM-CUR/PSM microspheres exhibited ROS/enzyme-responsive release profiles. CUR/PSM micelles demonstrated significant anti-CRC efficacy in cytotoxicity assays, cellular uptake studies, and cell migration assays. In AOM/DSS-induced CRC mice, KGM-CUR/PSM microspheres significantly improved survival and inhibited CRC tumor growth, and effectively reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase (MPO). Histopathological and microbiological analyses revealed near-normal colon architecture and microbial diversity in the KGM-CUR/PSM group, confirming the system’s ability to disrupt the “inflammation-microbiota-tumor” axis. Conclusions: The KGM-CUR/PSM microspheres demonstrated a synergistic enhancement of anti-tumor efficacy by inducing apoptosis, alleviating inflammation, and modulating the intestinal microbiota, which offers a promising stimuli-responsive drug delivery system for future clinical treatment of CRC. Full article