Search Results (12)

Poly(ε-caprolactone)-b-polysarcosine (PCL-b-PSar) block copolymers (BCPs) emerge as a promising alternative to conventional poly(ε-caprolactone)-b-poly(ethylene oxide) BCPs for biomedical applications, leveraging superior biocompatibility and biodegradability. In this study, we synthesized two series of PCL-b-PSar BCPs with controlled polymerization degrees (DP of PCL: 45/67; DP of PSar: 28–99) and low polydispersity indexes (Đ ≤ 1.1) and systematically investigated their crystallization-driven self-assembly (CDSA) in alcohol solvents (ethanol, n-butanol, and n-hexanol). It was found that the limited solubility of PSar in alcohols resulted in competition between micellization and crystallization during self-assembly of PCL-b-PSar, and thus coexistence of lamellae and spherical micelles. To overcome this morphological heterogeneity, we developed a modified self-seeding method by employing a two-step crystallization strategy (i.e., T_c1 = 33 °C and T_c2 = 8 °C), achieving conversion of micelles into crystals and yielding uniform self-assembled structures. PCL-b-PSar BCPs with short PSar blocks tended to form well-defined two-dimensional lamellar crystals, while those with long PSar blocks induced formation of hierarchical structures in the PCL₄₅ series and polymer aggregation on crystal surfaces in the PCL₆₇ series. Solvent quality notably influenced the self-assembly pathways of PCL₄₅-b-PSar₂₈. Lamellar crystals were formed in ethanol and n-butanol, but micrometer-scale dendritic aggregates were generated in n-hexanol, primarily due to a significant Hansen solubility parameter mismatch. This study elucidated the CDSA mechanism of PCL-b-PSar in alcohols, enabling precise structural control for biomedical applications. Full article

In recent years, ionic liquids (ILs) have served as potential solvents to dissolve organic, inorganic, and polymer materials. A copolymer (for example, Pluronic) can undergo self-organization by forming a micelle-like structure in pure IL medium, and its assembly depends upon the composition of IL. To evaluate the role of ILs, accurate coarse-grained (CG) modeling of IL is needed. Here, we modeled 1-ethyl-3-methylimidazolium dicyanamide ([EMIM][DCA]) ionic liquid (IL) using a CG framework. We optimized CG parameters for the [DCA]⁻ anion by tuning the non-bonded parameters and selecting different kinds of beads. The molecular density (ρ) and radial distribution function (RDF) of our CG model reveal a good agreement with the all-atom (AA) simulation data. We further validated our model by choosing another imidazolium-based cation. Our modified CG model for the anion shows compatibility with the cation and the obtained density matches well with the experimental data. The strategies for developing the CG model will provide a guideline for accurate modeling of new types of ILs. Our CG model will be useful in studying the micellization of non-ionic Pluronic in the [EMIM][DCA] IL medium. Full article

Bioactive linear choline-based copolymers were developed as micellar carriers for drug delivery systems (DDSs). The polymethacrylates containing trimethylammonium groups with p-aminosalicylate anions (PAS-based copolymers: series 1) or chloride anions (Cl-based copolymers: series 2) differing in ionic content and chain length were selected for drug loading. The diverse structures of amphiphilic copolymers made it possible to adjust the encapsulation efficiency of a well-known antibiotic, i.e., p-aminosalicylate in the form of sodium salt (PASNa) or acid (PASA), providing single drug systems. Goniometry was applied to verify the self-assembly capacity of the copolymers using the critical micelle concentration (CMC = 0.03–0.18 mg/mL) and the hydrophilicity level quantifying the surface wettability of polymer film using the water contact angle (WCA = 30–53°). Both parameters were regulated by the copolymer composition, indicating that the increase in ionic content caused higher CMC and lower WCA, but the latter was also modified to a less hydrophilic surface by drug encapsulation. The drug content (DC) in the PAS-based polymers was increased twice by encapsulation of PASNa and PASA (47–96% and 86–104%), whereas in the chloride-based polymer systems, the drug was loaded in 43–96% and 73–100%, respectively. Efficient drug release was detected for PASNa (80–100% series 1; 50–100% series 2) and PASA as complete in both series. The strategy of loading extra drug by encapsulation, which enhances the drug content in the copolymers containing anions of the same pharmaceutics, provided promising characteristics, which highlight the potential of PAS-loaded micellar copolymers for drug delivery. Full article

The short-term immediate release of supersaturated drug-delivery systems (SDDSs) presents an interesting process that can be tailored to multi-stage release events including initial release after dosing and dissolution, evolved release over longer dissolution periods for biological absorption, and terminal release following the end of immediate release. However, although comprehensive analysis of these critical release behaviors is often ignored yet essential for understanding the supersaturable immediate-release events for supersaturable solid formations when employing new techniques or polymers matched to a particular API. Hot-melt extrusion (HME) has become a popular continuous thermodynamic disordering technique for amorphization. The self-micellizing polymer Soluplus^® is reported to be a potential amorphous and amphiphilic graft copolymer frequently used in many nano/micro supersaturable formulations. Our current work aims to develop hypotensive supersaturating solid dispersion systems (faSDDS_HME) containing the BCS II drug, felodipine, when coordinately employing the HME technique and self-micellizing Soluplus^®, and to characterize their amorphization as well as immediate release. Other discontinuous techniques were used to prepare control groups (faSDDS_SE and faSDDS_QC). Tailored initial/evolved/terminal three-stage supersaturable immediate-release behaviors were identified and possible mechanisms controlling the release were explored. HME produced the highest initial release in related faSDDS_HME. During the evolved-release period, highly extended “spring-parachute” process was found in HME-induced amorphization owing to its superior supersaturation duration. Due to the enhanced crystallization inhibition effect, faSDDS_HME displayed the strongest terminal release as measured by solubility. For release mechanisms associated with HME, molecular interaction is not the likely dominant mechanism responsible for the improved properties induced by faSDDS_HME. For release mechanisms involved with the polymer Soluplus^® itself, they were found to inhibit drug recrystallization, spontaneously solubilize the drug and lead to improved molecular interactions in all SDDS systems, which were the factors responsible for the improved release. These mechanisms play an important role for the generation of an extended multi-stage immediate release produced via HME or self-micellizing polymer. This study provides a deeper understanding on amorphization and superior multi-stage supersaturable immediate-release behaviors for a particular hypotensive supersaturated delivery system combined with an HME-based continuous manufacturing technique and self-micellizing polymer strategy. Full article

A novel lysosome-targeting PEGylated polyester-based fluorescent pH nanosensor is fabricated by the combination of ring-opening copolymerization (ROCOP), side-group modification and subsequent self-assembly. First, a key target amphiphilic copolymer carrier for rhodamine (Rh) pH indicator is synthesized in a facile manner by the ROCOP of phthalic anhydride with allyl glycidyl ether using mPEG-OH and t-BuP₁/Et₃B as the macroinitiator and binary catalyst, respectively. Subsequently, Rh moieties are covalently attached on the polymer chain with controllable grafting degree via an efficient thiol-ene click reaction. Concurrently, the effect of catalyst systems and reaction conditions on the catalytic copolymerization performance is presented, and the quantitative introduction of Rh is described in detail. Owing to its amphiphilic characteristics, the rhodamine-functionalized polyester-based block copolymer can self-assemble into micelles. With the covalent incorporation of Rh moieties, the as-formed micelles exhibit excellent absorption and fluorescence-responsive sensitivity and selectivity towards H⁺ in the presence of various metal cations. Moreover, the as-prepared micelles with favorable water dispersibility, good pH sensitivity and excellent biocompatibility also display appreciable cell-membrane permeability, staining ability and pH detection capability for lysosomes in living cells. This work provides a new strategy for the facile synthesis of novel biocompatible polymeric fluorescent pH nanosensors for the fluorescence imaging of lysosomal pH changes. Full article

Achieving homogenous dispersion of nanoparticles inside a polymeric matrix is a great challenge for numerous applications. In the present study, we aim at understanding the role of different factors on the dispersion properties of TiO₂ in pluronic F-127 mixtures. The mixtures were prepared with different pH and guest/host ratios and investigated by UV-Vis spectroscopy, dynamic light scattering, infrared spectroscopy and electrical conductivity. Depending on the preparation conditions, different amounts of TiO₂ were loaded within the copolymer as quantitatively determined by UV-Vis spectroscopy. The different content of nanoparticles has direct implications on the gelation and micellization of pluronic analyzed by dynamic light scattering. The information derived on the self-assembly behavior was interpreted in relation to the infrared and conductivity measurements results. Together, these results shed light on the most favorable conditions for improving the nanoparticle dispersion inside the copolymer matrix and suggest a possible strategy to design functional nanoparticle-polymer systems. Full article

Targeted therapy by using nanomedicines based on the enhanced permeability and retention (EPR) effect is becoming a promising anticancer strategy. Many nano-designed photosensitizers (PSs) for photodynamic therapy (PDT) have been developed which show superior therapeutic potentials than free PS. To further understand the advantages of nano-designed PS, in this study, we used styrene-co-maleyl telomer (SMA) as a polymer platform to prepare a micellar type of PS with two well-characterized PSs—rose bengal (RB) and methylene blue (MB)—and evaluated the outmatching benefits of SMA-PS micelles, especially focusing on the singlet oxygen (¹O₂) generation capacity and intracellular uptake profiles. In aqueous solutions, SMA-PS self-assembles to form micelles by non-covalent interactions between PS and SMA. SMA-PS micelles showed discrete distributions by dynamic light scattering having a mean particle size of 18–30 nm depending on the types of SMA and different PSs. The hydrodynamic size of SMA-PS was evaluated by Sephadex chromatography and it found to be 30–50 kDa. In the presence of human serum albumin, the sizes of SMA-PS remarkably increased, suggesting the albumin-binding property. ¹O₂ generation from the SMA-PS micelle was determined by electron spin resonance, in which the SMA-PS micelle showed comparatively more photo-stable, and consequently a more durable and constant, ¹O₂ generation capability than free PS. Moreover, intracellular uptake of SMA-PS micelles was extensively faster and higher than free PS, especially in tumor cells. Taken together, SMA-PS micelles appear highly advantageous for photodynamic therapy in addition to its capacity in utilizing the EPR effect for tumor targeted delivery. Full article

Ophthalmic drug delivery is still a challenge due to the protective barriers of the eye. A common strategy to promote drug absorption is the use of ocular permeation enhancers, while an innovative approach is the use of polymeric micelles. In the present work, the two mentioned approaches were coupled by conjugating ocular permeation enhancers (PEG₂₀₀₀, carnitine, creatine, taurine) to an inulin-based co-polymer (INU-EDA-RA) in order to obtain self-assembling biopolymers with permeation enhancer properties for the hydrophobic drug dexamethasone (DEX). Inulin derivatives were properly synthetized, were found to expose about 2% mol/mol of enhancer molecules in the side chain, and resulted able to self-assemble at various concentrations by varying the pH and the ionic strength of the medium. Moreover, the ability of polymeric micelles to load dexamethasone was demonstrated, and size, mucoadhesiveness, and cytocompatibility against HCE cells were evaluated. Furthermore, the efficacy of the permeation enhancer was evaluated by ex vivo permeation studies to determine the performance of the used enhancers, which resulted in PEG₂₀₀₀ > CAR > TAU > CRE, while entrapment ability studies resulted in CAR > TAU > PEG₂₀₀₀ > CRE, both for fluorescent-labelled and DEX-loaded micelles. Finally, an increase in terms of calculated Kp and Ac parameters was demonstrated, compared with the values calculated for DEX suspension. Full article

Polylactide (PLA) is among the most common biodegradable polymers, with applications in various fields, such as renewable and biomedical industries. PLA features poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA) enantiomers, which form stereocomplex crystals through racemic blending. PLA emerged as a promising material owing to its sustainable, eco-friendly, and fully biodegradable properties. Nevertheless, PLA still has a low applicability for drug delivery as a carrier and scaffold. Stereocomplex PLA (sc-PLA) exhibits substantially improved mechanical and physical strength compared to the homopolymer, overcoming these limitations. Recently, numerous studies have reported the use of sc-PLA as a drug carrier through encapsulation of various drugs, proteins, and secondary molecules by various processes including micelle formation, self-assembly, emulsion, and inkjet printing. However, concerns such as low loading capacity, weak stability of hydrophilic contents, and non-sustainable release behavior remain. This review focuses on various strategies to overcome the current challenges of sc-PLA in drug delivery systems and biomedical applications in three critical fields, namely anti-cancer therapy, tissue engineering, and anti-microbial activity. Furthermore, the excellent potential of sc-PLA as a next-generation polymeric material is discussed. Full article

There is an urgent need for new strategies that allow the simultaneous detection and control of drug delivery. By making use of supramolecular host-guest interactions, a kind of pseudopolyrotaxanes, as a visualizable nanoscale drug carrier has been constructed by self-assembly of cucurbit[7]uril (CB[7]) with methoxy poly(ethylene glycol)-block-quaternized poly(4-vinyl pyridine) (mPEG-b-QP4VP) using 4-(chloromethyl)benzonitrile. Simple addition of CB[7] into an aqueous solution of mPEG-b-QP4VP resulted in noncovalent attachment of CB[7] to 4-cyanobenzyl-containing polymers, transforming the nonemissive mPEG-b-QP4VP micelles into highly fluorescent micelles. These pseudopolyrotaxanes micelles exhibited remarkable supramolecular assembly-induced emission enhancement and excellent biocompatibility, showing great potential for bioimaging applications. In addition, the efficient cellular uptake of the developed pseudopolyrotaxanes micelles loaded with the anticancer drug doxorubicin was a promising platform for simultaneous cell imaging and drug delivery, thereby widening their application in cancer theranostics. Full article

The differences in micro-environment between cancer cells and the normal ones offer the possibility to develop stimuli-responsive drug-delivery systems for overcoming the drawbacks in the clinical use of anticancer drugs, such as paclitaxel, doxorubicin, and etc. Hence, we developed a novel endosomal pH-sensitive paclitaxel (PTX) prodrug micelles based on functionalized poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) diblock polymer with an acid-cleavable acetal (Ace) linkage (mPEG-PCL-Ace-PTX). The mPEG-PCL-Ace-PTX₅ with a high drug content of 23.5 wt % was self-assembled in phosphate buffer (pH 7.4, 10 mM) into nanosized micelles with an average diameter of 68.5 nm. The in vitro release studies demonstrated that mPEG-PCL-Ace-PTX₅ micelles was highly pH-sensitive, in which 16.8%, 32.8%, and 48.2% of parent free PTX was released from mPEG-PCL-Ace-PTX₅ micelles in 48 h at pH 7.4, 6.0, and 5.0, respectively. Thiazolyl Blue Tetrazolium Bromide (MTT) assays suggested that the pH-sensitive PTX prodrug micelles displayed higher therapeutic efficacy against MCF-7 cells compared with free PTX. Therefore, the PTX prodrug micelles with acetal bond may offer a promising strategy for cancer therapy. Full article

The design and synthesis of enhanced membrane-intercalating biomaterials for drug delivery or vascular membrane targeting is currently challenged by the lack of screening and prediction tools. The present work demonstrates the generation of a Quantitative Structural Activity Relationship model (QSAR) to make a priori predictions. Amphiphilic macromolecules (AMs) “stealth lipids” built on aldaric and uronic acids frameworks attached to poly(ethylene glycol) (PEG) polymer tails were developed to form self-assembling micelles. In the present study, a defined set of novel AM structures were investigated in terms of their binding to lipid membrane bilayers using Quartz Crystal Microbalance with Dissipation (QCM-D) experiments coupled with computational coarse-grained molecular dynamics (CG MD) and all-atom MD (AA MD) simulations. The CG MD simulations capture the insertion dynamics of the AM lipophilic backbones into the lipid bilayer with the PEGylated tail directed into bulk water. QCM-D measurements with Voigt viscoelastic model analysis enabled the quantitation of the mass gain and rate of interaction between the AM and the lipid bilayer surface. Thus, this study yielded insights about variations in the functional activity of AM materials with minute compositional or stereochemical differences based on membrane binding, which has translational potential for transplanting these materials in vivo. More broadly, it demonstrates an integrated computational-experimental approach, which can offer a promising strategy for the in silico design and screening of therapeutic candidate materials. Full article