Efficient fabrication of tilt micro/nanopillars on polypropylene surface with robust superhydrophobicity for directional water droplet rebound.

The directional rebound and transport of water droplets plays an important role in microfluidic devices, anti-fogging, and water harvesting. Herein, an extrusion compression molding and directional stretch demolding method was used to prepare a polypropylene (PP) surface with tilt micro/nanopillars with a contact angle of 157 ± 3°. The rolling angle is the highest (9 ± 4°) when the direction of rotation is opposite the tilt direction of the micro/nanopillars, showing excellent water repellency and anisotropy of the surface. Compared with the position of the first collision of the water droplet, the position of the second collision shifted ∼1.5 mm along the tilt direction of the micro/nanopillars, driven by the surface tension component during the collision. The directional rebound behavior is controlled by the droplet energy and the tilt angle. The micro/nanopillars demonstrate excellent self-cleaning property and mechanical durability, which shows the possibility of their practical engineering applications.

pH-sensitive micelles self-assembled from multi-arm star triblock co-polymers poly(ε-caprolactone)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) for controlled anticancer drug delivery.

A series of amphiphilic 4- and 6-armed star triblock co-polymers poly(ε-caprolactone)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (4/6AS-PCL-b-PDEAEMA-b-PPEGMA) were developed by a combination of ring opening polymerization and continuous activators regenerated by electron transfer atom transfer radical polymerization. The critical micelle concentration values of the star co-polymers in aqueous solution were extremely low (2.2-4.0mgl(-1)), depending on the architecture of the co-polymers. The self-assembled blank and doxorubicin (DOX)-loaded three layer micelles were spherical in shape with an average size of 60-220nm determined by scanning electron microscopy and dynamic light scattering. The in vitro release behavior of DOX from the three layer micelles exhibited pH-dependent properties. The DOX release rate was significantly accelerated by decreasing the pH from 7.4 to 5.0, due to swelling of the micelles at lower pH values caused by the protonation of tertiary amine groups in DEAEMA in the middle layer of the micelles. The in vitro cytotoxicity of DOX-loaded micelles to HepG2 cells suggested that the 4/6AS-PCL-b-PDEAEMA-b-PPEGMA micelles could provide equivalent or even enhanced anticancer activity and bioavailability of DOX and thus a lower dosage is sufficient for the same therapeutic efficacy. The results demonstrate that the pH-sensitive multilayer micelles could have great potential application in delivering hydrophobic anticancer drugs for improved cancer therapy.

Self-assembled pH-responsive MPEG-b-(PLA-co-PAE) block copolymer micelles for anticancer drug delivery.

A series of amphiphilic pH-responsive poly (ethylene glycol) methyl ether-b-(poly lactic acid-co-poly (ß-amino esters)) (MPEG-b-(PLA-co-PAE)) block copolymers with different PLA/PAE ratios were designed and synthesized via a Michael-type step polymerization. The molecular structures of the copolymers were confirmed with (1)H NMR and gel permeation chromatography (GPC). These amphiphilic copolymers were shown to self-assemble into core/shell micelles in aqueous solution at low concentrations, and their critical micelle concentrations (CMC) in water were 1.2-9.5 mg/L. The pH-responsive PAE segment was insoluble at pH 7.4, but it became positively charged and soluble via protonation of amino groups at pH lower than 6.5. The average particle size and zeta potential of micelles increased from 180 nm and 15 mV to 220 nm and 40 mV, respectively, when the pH decreased from 7.4 to 5.0. Doxorubicin (DOX) was loaded into the core of these micelles with a high drug loading of 18%. The in vitro DOX release from the micelles was significantly accelerated when solution pH decreased from 7.4 to 5.0. DOX release in the first 10 h appeared to follow Fickian diffusion mechanism. Toxicity test showed that the copolymers had low toxicity whereas the DOX-loaded micelles remained high cytotoxicity for HepG2 cells. The results indicate the pH-sensitive MPEG-b-(PLA-co-PAE) micelle may be a potential hydrophobic drug delivery carrier for cancer targeting therapy with sustained release.

Synthesis and physicochemical characterization of amphiphilic triblock copolymer brush containing pH-sensitive linkage for oral drug delivery.

A novel and well-defined pH-sensitive amphiphilic triblock copolymer brush poly(lactide)-b-poly(methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether monomethacrylate) (PLA-b-PMAA-b-PPEGMA) and its self-assembled micelles were developed for oral administration of hydrophobic drugs. The copolymer and its precursors were synthesized by the combination of activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and ring-opening polymerization (ROP) techniques. The molecular structures and characteristics were confirmed by GPC, (1)H NMR, and FT-IR. The critical micelle concentration (CMC) values of PLA-b-PMAA-b-PPEGMA in aqueous medium varied from 1.4 to 2.6 mg/L, and the partition equilibrium constant (K(v)) of pyrene in micellar solutions ranged from 2.873 × 10(5) to 3.312 × 10(5). The average sizes of the self-assembled blank and drug-loaded micelles were 140-250 nm determined by DLS in aqueous solution. The morphology of the micelles was found to be spherical by SEM. Nifedipine (NFD), a poorly water-soluble drug, was selected as the model drug and wrapped into the core of micelles via dialysis method. The in vitro release behavior of NFD from the micelles was pH-dependent. In simulated gastric fluid (SGF, pH 1.2), the cumulative release percent of NFD was relative low, while in simulated intestinal fluid (SIF, pH 7.4), more than 96% was released within 24 h. All the results showed that the pH-sensitive PLA-b-PMAA-b-PPEGMA micelle may be a prospective candidate as oral drug delivery carrier for hydrophobic drugs with controlled release behavior.

Mesoscopic simulations on the aggregation behavior of pH-responsive polymeric micelles for drug delivery.

Computer simulations, dissipative particle dynamics (DPD) and mesoscopic dynamics (MesoDyn), are performed to study the aggregation behavior of pH-sensitive micelles self-assembled from amphiphilic polymer poly(methyl methacrylate-co-methacrylic acid)-b-poly(poly-(ethylene glycol) methyl ether monomethacrylate), P(MMA-co-MAA)-b-PPEGMA. Ibuprofen (IBU) is selected as the model drug. It can be seen from DPD simulations that P(MMA-co-MAA)-b-PPEGMA and IBU form spherical core-shell micelles at certain compositions, and IBU molecules distribute inside the core formed by hydrophobic MMA. The polymer molecules aggregate first, and then IBU diffuses into the aggregate, forming drug-loaded nanoparticles. With different compositions of polymer and IBU, aggregate morphologies in water are observed as sphere, column and lamella. From MesoDyn results, with less hydrophobic MMA beads, the polymer chains are more difficult to form ordered aggregates, and the order parameters get equilibrated in a longer time. The pH value also affects the aggregate process. At pH<5, the polymer could form traditional core-shell micelles. But at pH>5, the morphology of micelles is found to be anomalous and loose for releasing drug. MAA aggregates on the surface, instead of the inside. The simulation results are qualitatively consistent with the experimental results.

pH-Sensitive micelles self-assembled from amphiphilic copolymer brush for delivery of poorly water-soluble drugs.

A novel pH-sensitive amphiphilic copolymer brush poly(methyl methacrylate-co-methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether monomethacrylate) [P(MMA-co-MAA)-b-PPEGMA] was defined and synthesized by atom transfer radical polymerization (ATRP) technique. The molecular structures and characteristics of this copolymer and its precursors were confirmed by (1)H NMR, FT-IR, and GPC. The CMC of P(MMA-co-MAA)-b-PPEGMA in aqueous medium was determined to be 1-4 mg/L. This copolymer could self-assemble into micelles in aqueous solution with an average size of 120-250 nm determined by DLS. The morphologies of the micelles were found to be spherical by SEM and TEM. Ibuprofen (IBU), a poorly water-soluble drug, was selected as the model drug and wrapped into the core of micelles via dialysis method. Drug entrapment efficiency reached to 90%. The in vitro release behavior of IBU from these micelles was pH-dependent. The cumulative release percent of IBU was less than 20% of the initial drug content in simulated gastric fluid (SGF, pH 1.2) over 12 h, but 90% was released in simulated intestinal fluid (SIF, pH 7.4) within 6 h. The release profiles showed that the P(MMA-co-MAA)-b-PPEGMA micelles could inhibit the premature burst drug release under the intestinal conditions. All the results indicate that the P(MMA-co-MAA)-b-PPEGMA micelle may be a potential oral drug delivery carrier for poorly water-soluble drugs.