Polymeric Micelles Research Articles

As well-known nanocarriers for systemically injectable drug delivery systems, lipid-based polymeric micelles show potency for improving cancer treatment. Polyethylene glycol (PEG) is commonly used as a component of polymeric micelles owing to its biocompatibility but can cause immunogenic side reactions, which highlights the need for non-PEG-based systems for the delivery of therapeutic agents. To address this need, we herein synthesized a poly(N-{N'-[N″-(2-carboxyethyl)-2-aminoethyl]-2-aminoethyl}glutamide) [PGlu(DET-Car)]-lipid conjugate, prepared polymeric micelles with PGlu(DET-Car) surfaces, and investigated their physicochemical characteristics and in vivo performance. The micelles showed acidic pH-induced cellular uptake and endosomal escape behaviors superior to those of their PEG-based counterparts and elicited negligible immune responses, as revealed by antibody and cytokine production measurements. Thus, PGlu(DET-Car) presents itself as a viable alternative to PEG-based micelles a as smart drug carrier with specific sensitivity toward a narrow tumorous pH window and minimized immune reactions.

Stimulus-responsive nanocarriers are good candidates for targeted drug delivery. Herein, inspired by the existence of a clear threshold number of arginine residues in oligoarginines for cell-penetrating peptide (CPP) activity, we developed a strategy to control the CPP activity by changing the local arginine density for thermo-responsive targeting. We constructed polymeric micelles whose shell consists of a thermo-responsive polymer based on N-isopropylacrylamide, with a low density of arginine moieties (named Arg-TRM). At physiological temperature (37 °C), internalization of Arg-TRM into cells was small and comparable to that of micelle without arginine. In contrast, upon heating at 42 °C, the arginine density on the micellar surface was increased by thermo-responsive shrinkage of the shell, thereby switching on the CPP activity and enabling efficient cellular uptake. The response of Arg-TRM at 42 °C occurred within a few minutes and the intracellular uptake was rapidly enhanced from 5 min after the heating. This response was transient, thus enabling reversible control of the enhancement by heating. As proof-of-concept, we show that intravenously administered Arg-TRM was effectively accumulated in one ear of a normal mouse by local heating. These results indicate that Arg-TRM is a promising drug carrier for on-demand targeted drug delivery in response to mild external heating.

Polymeric micelles in advanced photodynamic therapy: Design, delivery and translational prospects

A solvent-free ropivacaine-loaded composite hydrogel assembled from pH-sensitive micelles and a thermosensitive injectable hydrogel for prolonged local anesthesia.

Fusobacterium nucleatum-targeted polymeric micelles disrupting biofilm-immune crosstalk for precision colorectal cancer immunotherapy

Baicalin-loaded micelles: Modulating M1 macrophages to overcome Lenvatinib resistance in anaplastic thyroid carcinoma.

Cannabidiol (CBD), a phytocannabinoid with therapeutic potential for neurological and other conditions, faces significant challenges in bioavailability due to its low water solubility, high lipophilicity, and extensive first-pass metabolism. Researchers have developed advanced nanodelivery systems addressing these limitations to enhance CBD’s absorption, stability, and efficacy. This review provides not only a comprehensive summary of current nanotechnological delivery strategies for CBD, including nanoemulsions, liposomes, polymeric micelles, nanosuspensions, and cyclodextrin inclusion complexes, but also introduces a distinct comparative and integrative perspective. Unlike previous reviews, our work synthesizes preclinical and clinical evidence while highlighting the novel integration of nanotechnology with bioenhancers and personalized medicine approaches. We further emphasize the emerging concepts of hybrid and smart nanocarriers, which have not yet been systematically discussed, positioning them as next-generation solutions to overcome CBD’s bioavailability challenges and paving the way for precision therapeutics.

This study examines how material selection governs the design, performance, and clinical translation of nanocarrier systems for anticancer drug delivery. By comparatively analyzing organic (e.g., liposomes, polymeric micelles, protein-based carriers) and inorganic platforms (e.g., gold nanoparticles, mesoporous silica, carbon-based materials), we delineate how biocompatibility, drugloading mechanisms, surface chemistry, and stimuli responsiveness shape pharmacokinetics, tumor accumulation, and release profiles. We highlight design rules that connect physicochemical parameterssize, charge, morphology, and ligand densityto biological outcomes such as enhanced permeability and retention, receptor-mediated uptake, and intracellular trafficking. Beyond single-material systems, we evaluate hybrid and coreshell architectures that integrate complementary strengths (biodegradability, structural robustness, imaging/theranostic capability) to enable controlled, site-specific delivery and real-time monitoring. Translational considerationsincluding scalable synthesis, Good Manufacturing Practice readiness, batch-to-batch quality attributes, and safety/clearance pathwaysare discussed as co-equal constraints with efficacy. This paper maps these considerations to clinical use-cases, noting where liposomes remain the regulatory benchmark, polymers offer programmable targeting and release, and inorganic or hybrid constructs unlock multifunctional therapies (photothermal, photoacoustic, or immuno-combination regimens). Finally, the author outlines a decision framework that aligns tumor biology (biomarkers, microenvironment, prior resistance) with nanocarrier typology to support personalized medicine. Collectively, the analysis provides practical guidance for matching material classes to therapeutic objectives, accelerating the trajectory from bench formulation to bedside impact in oncology.

Π-Π stacking stabilized polymeric micelles for hydrophobic drug delivery in the treatment of leishmaniasis.

Cancer treatment has changed significantly with the advent of EGFR-targeted TK inhibitors (TKIs), especially for non-small cell lung cancer (NSCLC). Despite their effectiveness, problems including acquired resistance, particularly the T790M mutation, and non-specific toxicity still exist. Recent developments in drug delivery, combination therapy, and knowledge of resistance mechanisms are addressing these issues. The efficacy of EGFR-targeted therapy has been demonstrated in a wide range of cancers, including head and neck and colorectal cancers. Genomic profiling informs precision medicine, which improves treatment approaches. Targeted cancer therapies, including kinase inhibitors and monoclonal antibodies, block specific signaling pathways essential for tumor growth, offering a more precise alternative to traditional chemotherapy. Moreover, nanotechnology enhances drug delivery, reduces toxicity, and overcomes resistance through advanced nanoparticles like polymeric micelles, PLGA, and chitosan, improving solubility, bioavailability, and sustained EGFR TKI release. This review discusses EGFR's significance in cancer therapy, the evolution of EGFR-targeted TKIs, resistance challenges, and advancements in nanotechnology-based drug delivery. We explore how polymeric and inorganic nanoparticles improve pharmacokinetics and targeted delivery, offering promising solutions to overcome resistance and enhance the therapeutic potential of EGFR-targeted therapies in personalized oncology.

BackgroundA rapid, simple, accurate, and robust reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed to quantify curcumin and dexamethasone in polymeric micelle nanoparticle formulations simultaneously.MethodsThe optimized chromatographic conditions involved a Universal HS C18 column, isocratic elution with a methanol: acidic water (pH 3.5, 80:20, v/v) mobile phase, and detection wavelengths of 425 nm for curcumin and 254 nm for dexamethasone. The developed method was subsequently validated according to ICH guidelines, and demonstrated excellent linearity (R2 > 0.999), precision (RSD% < 2%), and accuracy (mean recovery was 98.7% for curcumin and 101.7% for dexamethasone).ResultsThe limits of detection (LOD) were 0.0035 mg/mL for curcumin and 0.0029 mg/mL for dexamethasone, while limits of quantification (LOQ) were 0.0106 mg/mL for curcumin and 0.0088 mg/mL for dexamethasone, respectively. The method was applied to evaluate the encapsulation efficiency (EE%) of curcumin and dexamethasone into polymeric micelle nanoparticles formulated using Soluplus® and DOPE in a 1:10 molar ratio. EE% values were 78.84 ± 0.05% for curcumin and 54.33 ± 0.05% for dexamethasone.Conclusionsthe current developed method indicates suitability for the simultaneous determination of curcumin and dexamethasone, thereby facilitating the quality control and optimization of such advanced drug delivery systems.

ABSTRACT Macromolecules have emerged as transformative agents in drug delivery, significantly enhancing therapeutic efficacy, stability, and precision. These high molecular weight biomolecules, including nucleic acids, proteins, polysaccharides, and synthetic polymers, play a vital role in improving drug solubility, ensuring controlled release, and enabling targeted delivery while minimizing adverse effects. Recent advancements in material science and nanotechnology have led to the development of innovative drug delivery platforms such as hydrogels, dendrimers, liposomes, polymeric micelles, and nanoparticles. These sophisticated systems allow for precise drug administration, reducing toxicity and optimizing therapeutic outcomes. By leveraging macromolecular properties, researchers have enhanced drug bioavailability, improved targeting specificity, and enabled sustained and controlled drug release. The integration of macromolecules with nanotechnology is driving the next generation of drug delivery systems, offering groundbreaking solutions in nanomedicine.

Abstract Tandem reactions have received considerable attention in the past as an economic and ecological advantageous approach to carry out multi‐step reactions. The use of non‐compatible catalysts and which methods can be used to spatially separate them remains a major challenge. Here, we present a simplified approach to facilitate tandem reactions based on diblock copolymer micelles where the hydrophilic shell is functionalized with sulfonic acid groups and the micellar core contains l ‐proline as a second organo catalyst. Self‐assembly in water leads to block copolymer micelles that support a tandem reaction of a sulfonic acid catalyzed acetal cleavage in the micellar shell followed by a l ‐proline catalyzed aldol reaction in the micellar core. Three block copolymers were prepared with different ratios of SO 3 H and l ‐Proline groups within one block copolymer. Conversion of more than 95% for each reaction step and a syn / anti ratio of &gt;3/97 with high enantiomeric excess (&gt;95% ee) for the aldol product were achieved for the best block copolymer micelle. Moreover, the polymer micelles could be recycled in four consecutive runs and gave conversions of up to 98% for the acetal cleavage and 57% for the aldol reaction and proceeded with good enantio‐ (79% ee) and diastereoselectivity ( syn/anti = 4:96) in the 4 th run.

Obesity has become a major global health concern, contributing significantly to metabolic disorders, cardiovascular diseases, and diminished quality of life. Conventional therapeutic strategies, including lifestyle modification and pharmacotherapy, often demonstrate limited efficacy and are associated with systemic side effects. Recent advancements in pharmaceutical technology have enabled the development of innovative drug formulations and targeted delivery systems designed to enhance therapeutic efficacy while minimizing adverse effects. These emerging approaches include nanoparticle-based carriers, liposomes, polymeric micelles, and controlled-release formulations that improve bioavailability, enable site-specific targeting, and provide sustained drug release. Furthermore, combination therapies integrating anti-obesity agents with natural bioactive compounds are being explored for their synergistic potential. This review highlights recent trends in advanced drug formulation and delivery systems for obesity management, discussing their mechanisms, advantages, and clinical applications. Collectively, these novel strategies hold great promise for achieving safer, more effective, and personalized treatment outcomes in obesity management.

This review offers an in-depth exploration of the bioactivities, extraction techniques, formulation approaches and practical uses of naturally derived antioxidants in anti-ageing skincare. A critical analysis of the literature was performed. Extracts from leaves, aerial parts, seeds, peels, fruits and barks exhibit potent antioxidant, anti-inflammatory, photoprotective and anti-tyrosinase activities. Natural-based antioxidants exhibit a wide range of bioactivities as neutralizing free radicals through mechanisms such as metal chelation and activation of cellular antioxidant pathways (e.g. Nrf2/ARE) and anti-inflammatory effects by modulating cytokines like TNF-α and IL-6 and promoting wound healing by stimulating collagen synthesis and bioactive compound production. Extracts from Mucuna species, Magnolia officinalis and Arbutus unedo, for instance, demonstrate anti-ageing efficacy by inhibiting enzymes such as collagenase, elastase and MMPs. Certain fruit and seed extracts provide photoprotection with high SPF values, while others-such as mushroom extracts and essential oils-display potent antimicrobial activity. Their bioactivity is often enhanced through fermentation processes, innovative delivery systems like liposomes, niosomes and polymeric micelles, which improve stability, bioavailability and topical effectiveness. Extraction methods for natural antioxidants-including aqueous, hydroalcoholic, ultrasound-assisted (UAE), fermentation-assisted and alternative solvent (NaDES) techniques-are crucial for recovering and stabilizing bioactive compounds. Emerging green technologies such as supercritical CO2 extraction (SC-CO2), subcritical water extraction (SWE), supramolecular solvents (SUPRAS) and cloud point extraction (CPE) offer sustainable and selective recovery of bioactives with reduced environmental impact. These bioactives address oxidative stress, UV damage and dermal ageing, offering multifunctional applications in cosmeceuticals, pharmaceuticals and nutraceuticals. However, challenges such as photostability, inconsistent bioavailability and regulatory hurdles persist. Future research focusing on synergistic formulations, clinical validation and microbiome-friendly antioxidants will drive their advancement in next-generation sustainable skincare.

Polymeric micelles are promising nanocarriers for hydrophobic drug delivery, offering enhanced solubility, circulation time, and targeted release. This review presents a comprehensive evaluation of micelle preparation strategies, spanning conventional methods such as direct dissolution, dialysis, and thin-film hydration to emerging techniques including microfluidics, supercritical fluids, stimuli-responsive systems, and PEG-assisted assembly. Each method is compared in terms of scalability, reproducibility, solvent use, and regulatory compatibility. Among them, PEG-assisted methods show particular promise due to their simplicity and industrial readiness. We also explore the impact of fabrication strategy on drug loading, stability, and therapeutic efficacy across applications in cancer, infection, and inflammation. Finally, the review discusses key challenges in storage, manufacturing, and regulation, and highlights potential solutions through Quality-by-Design and scalable process integration. These insights provide guidance for the rational development of clinically translatable micelle-based drug delivery systems.

ZnO-Embedded Polymer Micelles as a Responsive Drug Delivery Carrier for Breast Cancer Therapy

The development of efficient and environmentally friendly herbicide-delivery systems is crucial in modern agriculture. Such systems can achieve precise targeting and controlled release of active ingredients through formulation technologies like slow-release carriers and targeted microcapsules. This study aims to synthesize a novel bio-based polymer through polycondensation of the natural product honokiol with triethylene glycol divinyl ether, and to evaluate its potential as a herbicide carrier. This study successfully synthesized an amphiphilic honokiol-based polymer. The resulting polymer micelle suspension, formed via self-assembly, exhibited a particle size of 130.5 nm, a critical micelle concentration of 3.8 × 10-3 mg/mL, a drug loading capacity of 13.79%, and an encapsulation efficiency of 82.75%. In vitro release studies demonstrated pH-dependent kinetics, with 80.1% cumulative release of diuron at pH 5.0 over 60 h, compared with only 16.35% at pH 7.0. Herbicidal activity tests against Echinochloa crus-galli demonstrated that the polymer micelle suspension achieved higher mortality rates and fresh weight reduction than diuron dispersion systems, attributable to their rhizosphere-triggered release properties, while significantly enhancing crop seedling safety. This study represents the first successful application of honokiol-based polymers in the field of herbicide delivery. The carrier system exhibits excellent controlled-release properties and synergistic effects, significantly enhancing herbicide utilization efficiency while reducing potential environmental risks. These findings provide a promising strategy and material foundation for developing a new generation of green pesticide formulations. © 2025 Society of Chemical Industry.

A phototriggered and pH-responsive cancer drug delivery system based on polymeric micelles was formulated, utilizing easily available and cost-effective materials such as an amphiphilic diblock copolymer (mPEG-PLA) and a Spiropyran derivative. It addressed the major challenges in drug delivery systems, i.e., monitoring real-time drug release, targeted, and on-demand drug delivery. To monitor real-time drug release, the fluorescence quenching of the cancer drug, doxorubicin (DOX), by in situ synthesized gold nanoparticles (AuNPs) through the Nanomaterial Surface Energy Transfer (NSET) mechanism was explored. Photoisomerization and size switching were characterized using UV-vis spectroscopy and dynamic light scattering (DLS) techniques. The NSET process during in situ synthesis of AuNPs and drug release from nanocarrier after 365 nm UV light exposure was demonstrated by steady-state and time-resolved fluorescence of DOX. The mPEG-PLA-Spiropyran-DOX (3:1:1) formulation exhibited ∼ 73.16% encapsulation efficiency and ∼ 6.45% DOX-loading with proven kinetic stability. Sustained DOX release over 50 h was validated through in vitro studies at pH 5.5, 6.5, and 7.4, showing enhanced DOX release at acidic pH 5.5, representative of cancer cell organelles with prolonged UV exposure. Cell internalization, intracellular phototriggered drug release, and fluorescence cell imaging in mouse breast adenocarcinoma cells (4T1) were investigated. The results demonstrated that the micellar nanocarrier, after 365 nm UV light exposure, was highly efficient in inducing apoptosis, significant cytotoxicity, and mitochondrial membrane depolarization. Furthermore, in vivo studies were conducted in both oral and breast cancer-bearing mice to assess tumor growth inhibition, changes in body weight, tumor weight, and immunohistochemical analysis. Notably, the therapeutic response was more pronounced in oral cancer, allowing for enhanced UV penetration and efficient activation of the micellar system. Overall, this study highlighted the potential of the dual-responsive micellar drug delivery system for targeted, on-demand cancer therapy with real-time monitoring. The enhanced efficacy in treating superficial malignancies underscores its promise for future clinical applications.

Herein, we report self-sorting systems of photoresponsive polymer micelles obtained from amphiphilic statistical copolymers bearing hydrophilic poly(ethylene glycol) (PEG) chains and hydrophobic/photoresponsive azobenzene (Azo) groups. The PEG/Azo copolymers self-folded or intermolecularly self-assembled via the association of the azobenzene pendants to form photoresponsive unimer or multichain micelles in water, where the core-forming Azo groups show cis/trans isomerization in response to UV/vis irradiation. The PEG/Azo copolymer micelles not only induced self-sorting in the presence of other PEG copolymer micelles with different compositions and/or pendants but also exhibited photoresponsive and reversible self-sorting/co-self-assembly with an anionic copolymer micelle via the cis/trans isomerization of the Azo units. We successfully developed self-sorting and co-self-assembly systems of binary polymer mixtures that can be dually controlled by molecular design and UV/vis light without using externally added reagents.