Iron oxide nanoparticles (IONP) are versatile materials that exhibit antibacterial properties through membrane damage and ROS production. However, the agglomeration tendency and poor colloidal dispersion in the aqueous medium limit their application. In this study, polymer-capped IONP were developed using three different polymers: polyethylene glycol (PEG 4000), polyvinyl pyrrolidone (PVP K-30), and hydroxypropyl methyl cellulose (HPMC E15) at three different concentrations (0.1%, 0.5%, and 1.0%) to prevent agglomeration and enhance IONP colloidal stability. The successful formation of the polymer-capped IONP was indicated by the hydrogen bond observed from the FT-IR spectrum, interference of the polymer in the crystal lattice of IONP, the smooth surface with an allegedly sheet-like structure, and less agglomerated particles. The application of a capping layer significantly reduced the hydrodynamic particle size of IONP from 140.00±27.90 nm to 82.20±10.14, 68.79±11.50, and 70.07±6.99 nm for IONP capped by PEG 1.0%, PVP 0.1%, and HPMC 1.0%, respectively. The disk diffusion antibacterial assay revealed a higher inhibition zone of the polymer-capped IONP than bare IONP towards Escherichia coli and Staphylococcus aureus. However, the minimum inhibitory concentration (MIC) determination using the microbroth dilution test possessed limitations in inhibiting bacterial growth due to insufficient direct contact of polymer-capped IONP with the bacterial membrane. The promising polymer-capped IONP systems for further development were IONP-PEG 1.0%, IONP-PVP 0.1%, and IONP-HPMC 1.0%, as depicted through Principal Component Analysis (PCA). The radical scavenging activity presented by polymer-capped IONP enhances its feasibility as an antibacterial agent for infectious diseases and antioxidant properties in the biomedical field.
Chronic wounds require dual-action therapies capable of managing localized microbial burdens while simultaneously promoting tissue regeneration. Although metronidazole (MTZ)-loaded chitosan/pectin (CS/Pec) polyelectrolyte complex (PEC) nanoparticles have been previously documented, the precise influence of the electrostatic charge ratio on their structure–property relationships and biological performance remains underexplored. In this study, crosslinker-free MTZ-loaded CS/Pec PEC nanoparticles were engineered via spontaneous aqueous electrostatic self-assembly to systematically investigate the effect of the negative-to-positive charge ratio (n-/n+). The findings demonstrate that electrostatic balance fundamentally dictates nanoparticle architecture, mass transport kinetics, and in vitro biological performance. The optimized formulation (n-/n+ = 0.17) yielded a favorable hydrodynamic diameter of 305.16 ± 11.06 nm, limited polydispersity (0.251 ± 0.05), and high colloidal stability (+25.78 ± 2.56 mV). This specific stoichiometric ratio also maximized drug loading, achieving an entrapment efficiency of 68.43 ± 3.15% and a loading capacity of 39.52 ± 2.19%, which were significantly higher than those of all other tested ratios (p < 0.05). In vitro release studies revealed a sustained, near-complete cumulative MTZ release of approximately 99% over 24 h, governed by anomalous non-Fickian transport mechanisms. Biologically, the optimized nanoparticles exhibited excellent cytocompatibility, yielding a fibroblast viability of >100%, which indicates that the polymeric matrix actively supports cellular metabolism. Furthermore, in vitro scratch assays, the MTZ-loaded PECs reduced the wound gap by 52% within 24 h, a 4- to 5-fold improvement over both the medium control and free MTZ. By establishing a rigorous structure–property relationship through systematic charge-ratio tuning, this study provides a rationally designed, cytocompatible foundation for the development of PEC-based nanocarriers in advanced wound management.
Obesity is a highly prevalent chronic disease, and lifestyle-based interventions often show limited long-term efficacy. Nanotechnology has emerged as a preclinical strategy to improve the bioavailability, stability, tissue delivery, and metabolic activity of anti-obesity agents. This systematic review evaluated the effects of nanostructure-based interventions in diet-induced obese murine models. Following PRISMA guidelines, searches of PubMed, Web of Science, and Scopus identified 26 eligible in vivo studies that included obese control groups and assessed obesity-related outcomes, including body weight, adiposity, fat mass, food intake, metabolic regulation, and related molecular pathways. Across heterogeneous nanoplatforms, nano-enabled interventions generally reduced body weight, adiposity, fat mass, adipose tissue accumulation, or obesity-associated metabolic dysfunction compared with obese controls. The reported mechanisms involved modulation of lipid metabolism, stimulation of fatty acid β-oxidation, inhibition of adipocyte differentiation, induction of browning-related thermogenic pathways, improvement of glucose–lipid homeostasis, and attenuation of inflammatory, oxidative, and endoplasmic reticulum stress signaling. However, these findings should be interpreted cautiously because the included studies differed substantially in nanomaterial composition, physicochemical properties, active compounds, route of administration, dose, treatment duration, obesity-induction protocol, and outcome assessment. In addition, the SYRCLE risk-of-bias assessment showed frequent unclear judgments in core methodological domains, particularly those related to randomization, allocation concealment, housing conditions, and blinding procedures. Several studies also provided limited information on animal characteristics, biodistribution, tissue accumulation, long-term safety, and toxicity. Overall, current evidence suggests that nanostructure-based anti-obesity interventions are biologically promising proof-of-concept strategies in preclinical murine models, rather than approaches ready for clinical translation. Future studies should incorporate standardized physicochemical characterization, transparent reporting of animal and experimental conditions, comparative head-to-head designs, biodistribution profiling, and long-term toxicity assessment before these platforms can be advanced toward human metabolic applications.
Bacterial biofilms are a major cause of persistent infections owing to their high tolerance to antimicrobial agents and host immune responses. In this study, two boron-functionalized carbon dots (CDs), boronic acid-derived carbon dots (BACD) and piperine/boronic acid-derived carbon dots (PPCD), were evaluated for their antibacterial, antibiofilm, and biofilm eradication activities against Staphylococcus epidermidis (SE) and Escherichia coli (E. coli). Both CDs exhibited concentration-dependent inhibition of bacterial growth, biofilm formation, and eradication of mature biofilms, with PPCD demonstrating superior activity and complete biofilm inhibition at concentrations ≥2.5 mg/mL. Hydroxyl radical generation together with membrane disruption and morphological changes suggest that oxidative stress contributes to the antibacterial activity. Cytocompatibility studies using human brain microvascular endothelial cells (HBMECs) showed minimal cytotoxicity at 0.1 mg mL⁻¹, while PPCD exhibited lower cytotoxicity than BACD at higher concentrations. These findings identify boron-functionalized CDs, particularly PPCD, as promising candidates for localized antibiofilm coatings and antimicrobial surface applications.
Catheter-associated urinary tract infection (CAUTI) is a prevalent healthcare-associated infection, necessitating alternative therapeutic strategies. Sericin-conjugated gold nanoparticles (AuNP-Sericin) offer broad antibacterial and biomedical potential, leveraging gold nanoparticles' inertness and low cytotoxicity with sericin's biocompatibility. This study aims to characterize the molecular mechanisms underlying AuNP-Sericin's antibacterial activity in human urine and to suggest its application in urinary catheters. Forty catheter-associated urine samples were collected for urinalysis and subsequently treated with AuNP-sericin for a proteomics-based molecular mechanism study. Additionally, the minimum inhibitory concentration of AuNP-sericin was determined against common uropathogens, including Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis, as well as against 10 single colonies derived from a urine sample. The scanning electron microscope revealed AuNP-sericin accumulation on microorganism cell surfaces via electrostatic interactions. This situation may disrupt membranes, block nutrient access, and thus interfere with microbial metabolic pathways. Proteomics investigation confirmed that AuNP-sericin can restrict microbial growth by trapping their membranes, interfering with translation and metabolism. In conclusion, AuNP-sericin can limit bacterial growth and biofilm formation, potentially reducing antibiotic consumption and UTI rates, which are major causes of hospitalization.
Biomass-derived nitrogen doped carbon dots (NCDs) were successfully synthesized using Spatholobus littoralis via a hydrothermal method and functionalized with L-histidine to enhance their fluorescence properties for dual applications in heavy metal ion detection and forensic fingerprint visualization. Structural and morphological characterization confirmed the formation of quasi-spherical carbon dots with an average particle size of approximately 6 nm and abundant surface functional groups, which contribute to strong photoluminescence behavior. The synthesized NCDs exhibited excellent fluorescence response and selectivity toward Cr⁶⁺ ions through a fluorescence quenching mechanism. The sensing system demonstrated good analytical performance with a LOD of 145.4 ppb and LOQ of 440.55 ppb for Cr⁶⁺. In addition, the practical applicability of the sensing platform was evaluated using spiked drinking water and tap water samples, where satisfactory recovery values ranging from 94.98% to 110.81% were obtained, confirming good accuracy and reliability for real sample analysis. Furthermore, the NCDs combined with tapioca powder demonstrated strong fluorescence and high contrast for latent fingerprint detection on non-porous surfaces under UV illumination. The developed multifunctional fluorescent material offers a promising, ecofriendly platform for simultaneous applications in environmental monitoring and forensic science.
Bacterial cellulose derived from coffee kombucha (KBC) is a renewable, biocompatible biopolymer; however, its limited intrinsic antimicrobial activity limits its biomedical applications. In this study, a sustainable and integrated biosynthetic approach was used to develop chitosan-reinforced, silver nanoparticle-decorated kombucha bacterial cellulose nanocomposite (KCBC-Ag). Silver nanoparticles (Ag NPs) biosynthesized by the coffee kombucha consortium had an average diameter of approximately 50 nm and were uniformly distributed within the cellulose matrix. The KBC-Ag exhibited potent antibacterial activity against Escherichia coli and Staphylococcus aureus, demonstrated high cytocompatibility toward HaCaT cells, and significantly improved wound closure in scratch assay (approximately 98% after 24 h). Additionally, the scaffold displayed favorable swelling properties and environmental degradability. These results indicate that KBC-Ag is a promising, sustainably fabricated wound dressing material that integrates biocompatibility, antibacterial performance, and regenerative capacity, with potential for biomedical applications.
Magnetic Resonance Imaging (MRI) is a high-resolution, noninvasive imaging method widely used in clinics, with imaging sensitivity enhanced by the contrast agent's ability to modulate proton relaxation times. Over the last few years, lanthanide nanoparticles have emerged as promising MRI contrast agents due to their strong magnetic properties and the convenient nanoscale engineering. Gadolinium-based nanoparticles have been widely utilized as T1-weighted contrast agents, while lanthanide-nanoparticles containing lanthanides holmium, dysprosium, and terbium have shown high potential as T2-weighted contrast agents. Nanoscale formulations enable enhanced relaxivity, colloidal stability, and surface functionalization, supporting targeted and multimodal imaging capabilities. However, increased interactions between nanoparticles and biological systems at the nanoscale raise particular concerns about cytotoxicity and biocompatibility. This review critically examines the in vitro cytotoxicity evaluation of lanthanide nanoparticles, emphasizing how physicochemical parameters, such as particle size and shape, surface charge, coating type, and cell type, influence biological responses. Various cell viability assays, including metabolism-based assays (MTT, MTS, WST, resazurin), cellular energy status (CellTiter-Glo), and membrane integrity (LDH), were used to observe the cytotoxic effects of nanoparticles. These studies show that rationally designed lanthanide nanoparticles, particularly those surface-functionalized with biocompatible coatings such as PEG, hyaluronic acid, or targeting ligands, exhibit minimal cytotoxicity and maintain high cell viability. Several aspects must be considered to achieve safe and effective nanoparticles as promising MRI contrast agents.
Electrospun nanofibers function not simply as release matrices, but as structural determinants of route-specific pharmacokinetic input and exposure. This review analyzes how nanofiber architecture, polymer composition, and drug-matrix interactions reshape route-specific pharmacokinetic behavior. Mechanistically, nanofibers influence pharmacokinetics by modifying dissolution rate, stabilizing amorphous drug states, regulating input functions, enhancing barrier interaction, and enabling localized depot formation. These effects translate into measurable pharmacokinetic outcomes, reduced fluctuation index, and decoupling of local tissue exposure from plasma concentrations.Mapping mechanistic design variables to dominant biological bottlenecks reveals that pharmacokinetic performance is fundamentally route-dependent. While oral systems frequently enhance systemic exposure through dissolution-driven absorption, mucosal and implantable nanofibers more commonly engineer spatially controlled local exposure with limited systemic spillover. Current in vivo evidence supports these route-specific pharmacokinetic advantages but remains heterogeneous, with limited systematic pharmacokinetic evaluation, weak in vitro-in vivo correlation, and minimal integration of physiologically based pharmacokinetic (PBPK) and pharmacokinetic-pharmacodynamic (PK-PD) modeling.This review introduces a route-aware pharmacokinetic design framework that integrates nanofiber architecture, biological bottlenecks, and graded levels of PK evidence to guide rational exposure engineering. The paper should be read as a mechanistic framework for organizing current evidence, rather than as a systematically conducted evidence synthesis. By positioning electrospun nanofibers as pharmacokinetic input-function shaping systems, this review proposes a route-aware design and evidence framework to guide rational development and translational assessment of nanofiber-mediated drug exposure.
In nanomedicine, accurately determining the entrapment efficiency (EE) and drug load (DL) of nanoparticles (NPs) is crucial for assessing their efficacy. EE represents the amount of drug encapsulated within the particles relative to the total drug used during manufacturing. Various methods, both direct and indirect, are employed for EE determination, each with its advantages and challenges. Separation techniques such as (ultra-)centrifugation, ultrafiltration, dialysis, and size exclusion chromatography are commonly used for isolating NPs from the suspension medium. Additionally, direct determination methods like high-performance liquid chromatography and UV/Vis spectroscopy may offer precise quantification of drug content within the particles. Lipid and polymeric NPs pose distinct challenges in EE determination, requiring careful consideration of factors such as solubility, stability, and particle density.Drawing attention to critical challenges and method validation, this work addresses the specific characteristics and methodological considerations for lipid and polymeric NPs. Through a comparative analysis of commonly used techniques, it underscores the importance of method validation and the need for standardised protocols. A decision tree in evidence-based selection of an EE methodology is proposed.In essence, this article serves as a comprehensive guide for scientists in the field of nanoparticle-based drug delivery, elucidating key considerations in formulation development, methodological approaches, and critical challenges for ensuring reproducibility and reliability in NP-based therapeutics.
Despite significant advances in antisense oligonucleotide (ASO) chemistry and nanocarrier design, therapeutic efficacy is often limited by inefficient cellular uptake and sequestration within endosomal–lysosomal compartments. Here, we show that ionizing radiation can be leveraged to overcome these barriers and enhance antisense nanomedicine delivery in castration-resistant prostate cancer (CRPC). CRPC cells (PC-3, C4-2) exhibited greater resistance to irradiation than castration-sensitive prostate cancer cells (LNCaP) and upregulated heat shock protein 27 (HSP27) in response to radiation, indicating an adaptive stress response. HSP27 downregulation by HSP27 mRNA -targeting ASO restored radiation-induced apoptotic signaling. To improve intracellular delivery, we developed lipid-modified ASOs (LASOs) targeting HSP27 mRNA that self-assemble into nanomicelles and enter cells via macropinocytosis. Although LASOs showed enhanced cellular uptake, they were predominantly sequestered within endosome–lysosome compartments, limiting their therapeutic activity. Strikingly, irradiation promoted endosomal-lysosomal escape of LASO nanomicelles, facilitating cytoplasmic delivery, robust HSP27 suppression, ultimately leading to increased anti-cancer effects, including an approximately 75% reduction in CRPC cell viability and delayed CRPC 3D spheroid growth. Collectively, these findings reveal a bidirectional therapeutic synergy in which HSP27 silencing resensitizes CRPC cells to radiation while irradiation enhances LASO intracellular trafficking. This study establishes irradiation as a trigger for intracellular drug release and provides a synergistic strategy integrating radiotherapy with antisense nanomedicine to overcome delivery barriers and restore therapeutic efficacy in CRPC.
Responsive nanomaterials have emerged as advanced platforms in modern therapeutics by enabling controlled drug release in response to specific internal and external stimuli. This review, “Emerging Frontiers of Responsive Nanomaterials in Drug Delivery Systems: From Design to Clinical Translation,” summarizes recent advances that highlight the importance of responsiveness in overcoming challenges such as heterogeneous disease microenvironments, off-target toxicity, and limited therapeutic control. Unlike conventional nanocarriers that rely mainly on passive targeting and continuous drug release, stimuli-responsive systems allow on-demand, site-specific, and temporally regulated drug delivery, improving efficacy while minimizing systemic side effects. These nanocarriers respond to biochemical cues, including pH, redox conditions, enzymes, and hypoxia, as well as physical triggers such as temperature, light, magnetic fields, and ultrasound. The review discusses major classes of responsive nanomaterials, including polymeric, lipid-based, inorganic, and hybrid nanoparticles, with emphasis on design strategies, stimulus-dependent release mechanisms, and disease-specific applications. Key challenges related to scalability, safety, reproducibility, and regulatory translation are addressed alongside emerging directions such as multi-stimuli-responsive systems, theranostics, AI-assisted nanodesign, and personalized nanomedicine.
Background The topical administration of azithromycin (AZ) is hindered by its low aqueous solubility, limiting its local availability for treating acne. Objective Develop and optimize an AZ-loaded nanoemulsion (AZ-NE) using tea tree oil (TTO) and incorporate it into a hyaluronic acid (HA) gel base to enhance solubility, residence time, and antibacterial activity against Propionibacterium acnes. Methods A Box–Behnken design was used to optimize TTO concentration, surfactant concentration, and sonication time with respect to globule size, polydispersity index (PDI), and viscosity. The optimized AZ-NE was incorporated into HA gel (1%, 1.5%, and 2%) to form nanoemulgels (AZ-NG), which were evaluated for in vitro release, skin irritation in rats, and antibacterial efficacy. Results Oil concentration significantly influenced droplet size, with the optimized AZ-NE exhibiting a particle size of 58.72 nm, PDI of 0.262, and viscosity of 98.4 cp. The 1.5% HA formulation (NG2) was selected as optimal, exhibiting pseudoplastic flow with a viscosity of 1671 cp, a spreadability of 4.21 cm, a pH of 5.72, and a drug content of 99.42%. In vitro testing showed that NG2 achieved 98% drug release within 6 hours, significantly higher than that of the AZ-loaded plain gel (63%). In vivo studies revealed no skin irritation. Furthermore, AZ-NG demonstrated superior antifungal activity with a zone of inhibition of 51 mm against P. acnes, compared to 38 mm for TTO and 32 mm for AZ-plain gel. Conclusion The developed AZ-TTO nanoemulgel proved effective for acne management, offering a synergistic antibacterial effect, enhanced dissolution, and safe topical application.
The use of chitosan in the green synthesis of metal nanoparticles influences biological recognition processes, which depend on the synthesis conditions, including pH value, temperature, and reaction time. This enables these nanostructures to be taken up at the subcellular level, causing changes in cellular biochemistry and homeostasis. The present research aimed to evaluate the cytotoxic and genotoxic effects generated in the in vitro model of human fetal ventricular cardiomyocytes (RL-14) in interaction with gold nanoparticles synthesized from high-molecular-weight chitosan (AuNPs-CsHMW). The nanoparticles were characterized by UV-Vis spectrophotometry, field-emission scanning electron microscopy, and Fourier-transform infrared spectroscopy. Additionally, the interaction between AuNPs-CsHMW and RL-14 cardiomyocytes was evaluated using trypan blue, comet assays, and mitochondrial membrane potential tests. The results showed that gold nanoparticles with colloidal stability, with apparent particle diameters between 12 nm and 30 nm, were obtained due to a pH value below the dissociation constant of chitosan. Cardiomyocytes' responses to nanoparticles were observed, with cellular viability ranging from 83% to 92%, DNA content in the head ranging from 84% to 92%, and variations in mitochondrial membrane potential. Modifying the biocompatibility response in relation to nanoparticle concentration and interaction time with the cell syncytium.
Stimuli-responsive nanoparticles (NPs) are a major improvement to standard drug delivery methods because these allow the release of therapeutic agents in response to a particular biological response. Individual-stimuli-responsive systems, designed to react to a single stimulus (pH, temperature, redox gradient, etc.), have been shown to make more therapeutic impact and less systemic toxicity than non-responsive preparations. Nevertheless, the heterogeneity and complexity of most disease microenvironments, like the concomitant gradients of pH, expression of enzymes, and hypoxia in solid tumors, frequently surpass the discriminative ability of a solitary stimulus. This may result in inappropriate targeting or the early release of drugs in non-diseased tissues that may also have the triggering condition. The use of multi-stimuli-responsive block copolymers in the nanomaterial system addresses the drawbacks of the single-stimuli-responsive system. This system surpasses the risk of off-target pharmaceutical release. These discharge encapsulated substance upon the presence of several cues, including low pH, high ROS, temperature, light, and the presence of intracellular enzymes, in a variety of biomedical conditions, including cancers, diabetes and metabolic disorders, autoimmune inflammatory diseases, neurological disorders and bacterial infections. The multi-stimulus-responsive NPs have increased activation potential due to their ability to be responsive to a variety of pathological cues related to the disease status, thus ensuring better therapeutic outcomes. Regardless of this heterogeneous promise, their clinical application poses significant challenges of dysregulated immune activation, biocompatibility, batch-to-batch variation, and the absence of standardized regulatory pathways.The objective of the present review includes examining and considering the various forms of internal and external stimuli and their incorporation into one nanoplatform to treat a wide range of biomedical conditions. This review prominently emphasizes the design of various stimuli-responsive NPs along with their preparation techniques and regulatory hurdles for their clinical utilization.
Docetaxel (DTX) has limited therapeutic efficacy due to its poor water solubility and intestinal permeability. To improve DTX therapeutic effect, we aimed to design supramolecular nanoparticles (SNPs) of DTX and sulfobutylether-β-cyclodextrin (SBE7-β-CD). SNPs were finally synthesized by incorporation of DTX-SBE7-β-CD inclusion complexes in nanoparticulate structure of chitosan ionically crosslinked with sodium tri polyphosphate (STPP). Supramolecular nanoparticles (SNPs) showed particle size (372 ± 126.9 nm) with low polydispersity index and narrow size distribution possessing positive zeta potential (19.9 ± 6.66 mV). H1 NMR revealed DTX is complexed with SBE7-β-CD with non-covalent bonding. DTX-SBE7-β-CD loaded nanoparticles gave maximum increase in drug loading and encapsulation efficiency (500 ± 0.01 µg/mg, 82.95 ± 0.15 %), respectively. Drug release followed fickian diffusion mechanism with negligible release at acidic pH and higher release at basic pH. Further, significant increase in AUC, Cmax, and Tmax was observed with SNPs than oral administered DTX. SNPs administered to healthy rabbits for toxicity evaluation in major organs showed reversible changes in kidney tissues along absence of severe toxicity in heart and liver tissues. SNPs significantly increased cytotoxic activity in MDA-MD-231 cancer cell lines. Hence, our work demonstrated SNPs are suitable for oral delivery of DTX with maximum therapeutic outcomes.
Over the last fifteen years, dendrimers as drug delivery systems have evolved from simple carrier systems to advanced, stimuli-responsive systems capable of modulating drug release in response to internal (e.g., pH, enzymes) and external (e.g., temperature, magnetic field) stimuli. Such advancements have made them highly promising for spatiotemporal control, enhanced therapeutic efficacy, and personalized medicine. Dual - and multi-stimuli responsive dendrimers have attracted interest because they readily incorporate various natural or artificial triggers, enabling accurate and safe drug release in complex biological environments. These formulations have also contributed to modulating drug release after administration through various routes, including oral, transdermal, and relatively less explored routes such as buccal. Commonly used components in dendrimer-based formulations include drugs, dendrimers, solvents, ligands, nanoparticles as cores, and solubilizing agents. The aim of this review is therefore to critically analyse literature from the last 15 years that discusses various stimuli-responsive dendrimeric formulations studied across different routes of administration in drug delivery. It highlights various linker chemistries and surface engineering strategies used to control drug release in response to a stimulus. The review also examines how various routes of administration affect the release patterns and therapeutic performance of the formulation, thereby serving as a practical roadmap for researchers developing precision nanomedicines. Finally, the current drawbacks/limitations of stimuli-responsive dendrimers, including in vivo specificity, biocompatibility, scalability, reproducibility, and obstacles to clinical translation, are critically reviewed.
Nanoformulation platforms have transformed drug delivery; however, reliable scale-up from laboratory to manufacturing remains the principal barrier to clinical translation. This review integrates target product profile (TPP)–driven requirements with critical quality attributes (CQAs), platform-specific unit operations, and Quality by Design (QbD) principles to analyze scalable manufacturing of five major nanoformulation classes—lipid/liposome, polymeric/micellar, nanoemulsion, nanocrystal, and albumin/biopolymer systems—which collectively represent over 80 % of clinically approved nanomedicines. Quantitative analysis across these platforms demonstrates that controlled micromixing and solvent displacement routinely yield lipid and polymeric nanoparticles in the 50–200 nm range, while energy density–constrained high-pressure homogenization governs droplet size distributions in nanoemulsions, and stress intensity and stabilizer adsorption dictate nanocrystal quality. Protein-based carriers are shown to be particularly sensitive to raw-material variability and crosslinking kinetics. Five industrial case studies (Doxil®/CAELYX®, Onpattro®, Comirnaty®, Abraxane®, and AmBisome®) illustrate how orthogonal analytics (e.g., DLS and AF4–MALS), closed single-use architectures, and digitally enabled QbD–PAT frameworks link critical process parameters (CPPs) to robust control strategies across development and commercial manufacture. Overall, the review highlights standardization, quantitative comparability, and data-driven control as central enablers of scalable and regulatory-ready nanomedicine manufacturing.
Nanoparticle-based drug delivery systems have the potential to provide a promising platform for overcoming the limitations of therapeutics in cancer treatment, thanks to advantages such as controlled release, tumor targeting, and reduced systemic toxicity. In parallel, microalgal biomolecules possess strong antioxidant and antiproliferative properties. However, these biomolecules are therapeutically limited due to their low stability and restricted bioavailability. The approach of using microalgal compounds in combination with nanoparticles both improves their pharmacokinetic properties and enhances multiple anticancer mechanisms (ROS modulation, caspase activation, etc.). This review focuses on the anticancer potential of microalgal biomolecules and nanoparticulate systems, the intracellular mechanisms of action of the conjugated platforms they form, and their biocompatibility advantages. It also describes the potential of conjugated platforms for future clinical applications, highlighting their importance as biologically synergistic and targeted next-generation therapeutic platforms in cancer treatment.
Effective cancer immunotherapy requires cytosolic delivery of antigens into dendritic cells together with their maturation to elicit robust cellular immunity. Conventional vaccine carriers often combine multiple components to achieve both adjuvant activity and antigen delivery, which increases formulation complexity and raises safety concerns. Here, we present a strategy to integrate these functions into a single material by synthesizing carboxylated curdlan derivatives with tailored spacer structures. Introducing carboxy groups into curdlan, a representative polysaccharide adjuvant, conferred pH-sensitivity and improved water solubility, while spacer hydrophobicity modulated protonation behavior and interactions with lipid membranes. Among the derivatives, Chex-Curd, bearing a cyclohexyl spacer within carboxylated units, exhibited strong adjuvant activity and enhanced antigen presentation via the MHC class I pathway, which might result from cytosolic delivery of antigen. Chex-Curd also induced high levels of TNF-α and IL-12 secretion and upregulated dendritic cell maturation markers. Conjugates of Chex-Curd with a model antigenic protein elicited strong CD8⁺ T-cell responses and achieved significant tumor growth suppression in a mouse tumor model. These findings demonstrate that spacer engineering of polysaccharide-based adjuvants enables simultaneous dendritic cell activation and cytosolic antigen delivery, providing a promising platform for next-generation cancer vaccines.
