Pluronic Micelles Research Articles

Pluronic based injectable smart gels with coumarin functional amphiphilic copolymers

Temperature responsive Pluronic F127 micelles were combined with light-responsive coumarin bearing amphiphilic copolymers to obtain both mechanically strong and injectable gels. For this purpose two monomers, 7-(2-methacryloyloxyethoxy)-4-methylcoumarin (CEMA) and 7-methacryloyloxy-4-methylcoumarin (CMA), were synthesized and further polymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Well-defined amphiphilic diblock terpolymers were obtained by using preliminarily synthesized polyethylene glycol (PEG) based macroRAFT agent. The structures of copolymers were confirmed with proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier-transform infrared(FT-IR) spectroscopy and gel permeation chromatography (GPC) analyses. Amphiphilic diblock terpolymers self-assembled into micelles in aqueous solution spontaneously and crosslinking of the micelle cores through the photodimerization of coumarin groups under UV irradiation at 350 nm was examined by UV spectroscopy. Hydrogels were prepared using two different methods, PF127-Mx gels formed using polymer micelle solutions with PF127 solid and PF127-Px gels formed by mixing solid polymers with 20 % F127 solution. Upon characterization of hydrogels via dynamic light scattering (DLS) and transition electron microscope (TEM), rheological properties of the gels were evaluated as a function of temperature, composition, UV exposure time, strain and frequency. Injectability tests of hydrogel systems were performed on a texture analyzer and all the formulations were found in the injectable range. The study reveals that hydrogels based on combination of PF127 and coumarin functional terpolymer amphiphiles hold great potential as injectable biomaterials.

Nanocomposite conductive tough hydrogel based on metal coordination reinforced covalent Pluronic F-127 micelle network for human motion sensing

The design of conductive hydrogels integrating anti-fatigue, high sensitivity, strong mechanical property and good sterilization performance remains a challenge. We innovatively introduced metal coordination in covalently crosslinked Pluronic F-127 micelle network and synthesized nanocomposite conductive tough hydrogel through the combination of covalent crosslinking, metal coordination and silver nanowire reinforcement. Compared with pure diacylated PF127 hydrogel (PF127), the tensile strength of PF-AA-AM-Al3+/Ag0.25 hydrogel reaching 1.4 MPa was about 10 times than that of PF127. The toughness of PF-AA-AM-Al3+/Ag0.25 reaches 1.88 MJ/m3. Compared with PF-AA-AM-Al3+, the introduction of silver nanowires increased the fatigue life of PF-AA-AM-Al3+/Ag0.25 by 200% (31837 cycles), 170% (12804 cycles) and 1022% (511 cycles) under 100%, 120% and 150% ultimate tensile strains, respectively. Besides, the PF-AA-AM-Al3+/Ag0.25 showed strain sensitivity to small deformation (Gauge factor = 2.42) in wearable tests on hands and knees. In addition, the PF-AA-AM-Al3+/Ag0.25 had good cytocompatibility and antibacterial performance that bacteria killing ratio of 98% to S. aureus and 99% to E. coli. Finally, a viscoelastic numerical constitutive model was established based on finite element method to study the damage failure history of the material. Comparative analysis showed that local stress concentration was the main factor leading to the failure of hydrogel.

Labrasol mediated enhanced solubilization of natural hydrophobic drugs in Pluronic micelles: Physicochemical and in vitro release studies

In present work, the solubilization of two natural hydrophobic drugs Quercetin (QCT) and Curcumin (CUR) has been systematically investigated in Pluronics (P84, F127, F68) and Pluronics-Labrasol mixed micelles. UV–Visible studies confirmed that the solubility, drug loading efficiency, partition coefficient (P), standard free energy of solubilization (ΔG°) of QCT and CUR were significantly higher in Pluronic P84 and P84-Labrasol mixed micelles than other investigated systems. Solubilization locus of both drugs in pluronic and Pluronic-Labrasol mixed micelles was scrutinized by employing DPV measurments. Enhanced solubilization of both drugs in Pluronic P84 and P84-Labrasol mixed micellar solution is also well supported by increased fluorescence intensity in respective fluorescence titrations. Inferences from Dynamic light scattering (DLS) studies revealed that the hydrodynamic diameter (Dh) of Pluronic-Labrasol mixed micelles is smaller than pure Pluronic micelles. Upon the inclusion of QCT and CUR, Dh of both Pluronic and Pluronic-Labrasol mixed micelles was found to be increased. Pluronic and Pluronic-Labrasol mixed micellar formulations exhibited the sustained release behaviour for both QCT and CUR. The improved solubilization of QCT and CUR may serve as an efficient system for sustained drug delivery enabling enhanced oral absorption and bioavailability.

Physicochemical Characterization of Berberine-loaded Pluronic F127 Polymeric Micelles and In Vivo Evaluation of Hypoglycemic Effect

Physicochemical Characterization of Berberine-loaded Pluronic F127 Polymeric Micelles and In Vivo Evaluation of Hypoglycemic Effect

New trans-[Ru(NO)(NO2)(dppb)(o-bdqi)]+ complex as NO donor encapsulated Pluronic F-127 micelles

Ruthenium complexes that act as nitric oxide (NO) donors show potential cytotoxicity in tumor models. In this work, we proposed the synthesis of the new nitrosyl ruthenium complex trans-[Ru(NO2)(NO)(dppb)(o-bdqi)]Cl2, containing a non-innocent ligand of the o-phenylenediamine type (o-bdqi). The 31P{1H} NMR spectra confirmed that the trans-[Ru(NO2)(NO)(dppb)(o-bqdi)] is the isomer formed. The complex was characterized by elemental analysis, mass spectrometry, UV–vis and infrared spectroscopy and cyclic voltammetry. Natural transition orbitals (NTOs) for trans-[RuCl2(dppb)(o-bdqi)] and trans-[Ru(NO2)(NO)(dppb)(o-bdqi)]Cl2 complex were obtained with TD-DFT/B3LYP methodology to contribute to the assignment of electronic transition. A micellar system (F-127/Ru) produced with Pluronic F-127 copolymer was used as a drug delivery system, due to the hydrophobicity of the complex. The F-127/Ru system showed NO release in aqueous media. The free complex showed higher cytotoxicity than the F-127/Ru system in the studied tumor cells. However, the F-127/Ru system showed a higher selectivity index for lung cells. This shows that the Pluronic F-127 carrier can be a good alternative in the use of hydrophobic nitrosyl ruthenium compounds in the treatment of some types of cancer.

Development of Bromfenac Sodium Loaded Pluronic Nanomicelles: Characterization and Corneal Permeation Study.

The Cataract is the leading cause of visual impairment and preventable blindness worldwide. Cataract removal surgery involves various post-operative complications like pain and inflammation. The objective of this study is to screen the polymer concentration as well as optimize the formulation components to develop the pluronic micelles with nanosized characterization and for enhanced corneal permeation study. For optimization, Central Composite design was employed to study the effect of independent variables, concentration of Pluronic F 127 (X1) and the concentration of Hyaluronic acid (X2) on chosen responses (Y 1 ) Micelle size, (Y 2 ) Entrapment Efficiency, (Y 3 ) Viscosity. The lyophilised powder was used for physical characterisation. The formulation containing 5%w/v Pluronic F127 and 0.2%w/v Hyaluronic acid was the optimised composition with micelle size and zeta potential 38.74±4.12nm and -17.6±0.1 mV respectively. In-vitro drug release was found to be 91.72±1.2 percentage in 8 hours. Surface morphology revealed micelles were spherical in shape. Ocular irritancy study showed that formulation was safe and non-irritant. In vitro corneal permeation studies through excised rabbit cornea indicated 1.5 fold increase in ocular availability without corneal damage compared to an aqueous suspension containing the same amount of drug in nanomicelles. In a nutshell, Pluronic Nanomicelles would be a platform for the delivery of Bromfenac Sodium.

Sustained Activity of Stimuli-Responsive Curcumin and Acemannan Based Hydrogel Patches in Wound Healing.

Natural plant extract, namely acemannan (Ac) and curcumin (Cur), coencapsulated pluronic micelles, showing thermoresponsive properties, were designed for efficient and safe in vivo wound healing applications. Ac and Cur, widely used antimicrobials, find limited applications because of their low stability, short biological half-life, poor solubility, and low bioavailability. Herein, we report the extraction of Ac from aloe vera and coencapsulation of it with Cur in pluronic micelles to take advantage of the combined effects of both components. Both Ac and Cur preserved their bioactive functionality upon encapsulation. Single photon emission computed tomography imaging confirmed that NPAcC2 hydrogel masked the whole wound by forming a layer. Cur and Ac synergistically resulted in rapid wound closure on the seventh day, and full-grown hair was observed on the 10th day. Individually they both take more than 20 days for wound closure. The increase in the concentration of curcumin increases the healing properties of the material. For days 1, 6, and 10 of the wound dressing experiment, the percentages of wound closure of the mice were the highest for NPAcC2 (i.e., 100%) compared to the untreated control (25%) while maintaining the integrity of the skin. These natural product-based hydrogels have limited side effects vs those caused by commercial drugs in wound healing.

Sodium dodecyl sulfate modulates the structure and rheological properties of Pluronic F108-poly(acrylic acid) coacervates).

Micelles formed within coacervate phases can impart functional properties, but it is unclear if this micellization provides mechanical reinforcement of the coacervate whereby the micelles act as high functionality crosslinkers. Here, we examine how sodium dodecyl sulfate (SDS) influences the structure and properties of Pluronic F108-polyacrylic acid (PAA) coacervates as SDS is known to decrease the aggregation number of Pluronic micelles. Increasing the SDS concentration leads to larger water content in the coacervate and an increase in the relative concentration of PAA to the other solids. Rheological characterization with small angle oscillatory shear (SAOS) demonstrates that these coacervates are viscoelastic liquids with the moduli decreasing with the addition of the SDS. The loss factor (tan δ) initially increases linearly with the addition of SDS, but a step function increase in the loss factor occurs near the reported CMC of SDS. However, this change in rheological properties does not appear to be correlated with any large scale structural differences in the coacervate as determined by small angle X-ray scattering (SAXS) with no signature of Pluronic micelles in the coacervate when SDS concentration is >4 mM during formation of the coacervate, which is less than that observed (6 mM SDS) in initial Pluronic F108 solution despite the higher polymer concentration in the coacervate. These results suggest that the mechanical properties of polyelectrolyte-non-ionic surfactant coacervates are driven by the efficicacy of binding between the complexing species driving the coacervate, which can be disrupted by competitive binding of the SDS to the Pluronic.

Superstable and Large-Scalable Organosilica-Micellar Hybrid Nanosystem via a Confined Gelation Strategy for Ultrahigh-Dosage Chemotherapy

Although various drug nanocarriers have been developed for treating solid tumors, their clinical transformation is greatly limited by the difficulties in quantity production and unpredictable in vivo toxic effects. Herein, a facile "confined-gelation" strategy is developed to quantity-produce intelligent pluronic organosilica micelles (designated as IPOMs) with an undetectable critical micelle concentration (CMC), which features the self-assembly induced core confinement by block copolymers, the inner hydrolysis-condensation of silane to the oligomer skeleton, and oxidative cross-linking of disulfide skeleton to core gelation. The docetaxel-loaded IPOMs (DTX@IPOMs) with precise glutathione (GSH) responsiveness not only display an ultrahigh tolerated dose (360 mg/kg) in healthy Kunming mice model but also exhibit a remarkable tumor inhibition efficacy in both subcutaneous and orthotopic mice tumor models upon an extraordinarily large dosage (50 mg/kg). The present confined-gelation strategy provides a novel pathway to design and quantity-produce low-toxic and high-efficacy organic-inorganic hybrid nanodrugs in future clinical transformations.

Structure and composition of mixed micelles formed by nonionic block copolymers and ionic surfactants in water determined by small-angle neutron scattering with contrast variation

HypothesisComplex fluids comprising polymers and surfactants exhibit interesting properties which depend on the overall composition and solvent quality. The ultimate determinants of the macroscopic properties are the nano-scale association domains. Hence it is important to ascertain the structure and composition of the domains, and how they respond to the overall composition. ExperimentsThe structure and composition of mixed micelles formed in aqueous solution between poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers (Pluronics or Poloxamers) and the ionic surfactant sodium dodecylsulfate (SDS) are determined from an analysis of small-angle neutron scattering (SANS) intensity data obtained at different contrasts. Different polymers and concentrations have been probed. FindingsThe SDS + Pluronic mixed micelles include polymer and some water in the micelle core that is formed primarily by alkyl chains. This is different than what was previously reported, but is consistent with a variety of experimental observations. This is the first report on the structure of SDS + Pluronic P123 (EO19PO69EO19) assemblies. The effects on the mixed micelle structure and composition of the surfactant concentration and the polymer hydrophobicity are discussed here in the context of interactions between the different components.

Hyaluronic acid coated Pluronic F127/Pluronic P123 mixed micelle for targeted delivery of Paclitaxel and Curcumin

The hydrophobicity of most of the anticancer drugs offers a great challenge in selecting a system for their effective transport. Here comes the importance of micelles that offers a hydrophobic core for incorporating these drugs. In this study, Hyaluronic Acid coated Pluronic mixed micelle loaded with Paclitaxel and Curcumin was designed and evaluated its anticancer activity in MCF-7 cells. Pluronic F127 (PF127) and Pluronic P123 (PP123) were taken for preparing the mixed micelles. The targeting ligand folic acid (FA) was conjugated to one end of PP123 forming FA-PP. The end hydroxyl groups of PF127 were oxidized to aldehyde groups resulted in PF-CHO. Mixed micelles were prepared from PF-CHO and FA-PP and the end aldehyde groups were used for coating the micelles with hyaluronic acid. The material was characterized using FTIR, H1NMR, DLS, FE-SEM and TEM. The coated micelles showed spherical shape with drug loading efficiency of 50.15 and 65.05% for Paclitaxel and Curcumin, respectively. In vitro drug release was studied at pH 5.5 and 7.4. Dual drug-loaded material showed higher in-vitro anticancer activity than free Paclitaxel and Curcumin. The results suggested that synthesized mixed micelle with dual drugs showed great potential for targeted delivery to MCF-7 cells.

Enhanced Solubility and Oral Bioavailability of Hydrophobic Drugs Using Pluronic Nanomicelles: An In‐Vitro Evaluation

AbstractPoor drug solubility and oral bioavailability is a significant challenge with many effective drug candidates. Pluronic micelles are effective solutions for improved solubility, stability, and delivery of the hydrophobic drug to the right area, at the right time, and in the right amount. Solubilization of three drugs, namely curcumin (CUR), quercetin (QCN), and lamotrigine (LTG), were explored using Pluronics with varying molecular characteristics. All the drugs showed better solubility in Pluronic solutions. The tendency of augmentation in solubility was QCN>CUR>LTG. Results showed better solubilization of drugs in Pluronics which form micelles and have low CMTs. With an objective to enhance the oral bioavailability of drugs, the drug‐loaded Pluronic P123 nanomicelles (PLC for CUR, PLQ for QCN, and PLL for LTG) have been prepared and characterized using UV‐VIS, DLS, SANS, CPT, and TEM measurements. The drug‐loaded P123 nanomicelles having particle sizes range from 18 to 22.5 nm and spherical in shapes. In the in‐vitro release study, CUR and QCN showed slow release,while LTG exhibited a faster release profile. The PLC and PLQ assessed their anti‐oxidant potential had confirmed the oxidation resistance more significantly than the free drug. Considering the pharma uses of CUR, QCN, and LTG drugs and observing the application of Pluronics in drug delivery systems, the present work facilitates insight into the possible formulations of these drugs.

Pluronic F127 micelles improve the stability and enhance the anticancer stem cell efficacy of citral in breast cancer.

Aim: Improving the stability and anti-cancer stem cell (CSC) activity of citral, a natural ALDH1A inhibitor. Materials & methods: Citral-loaded micelles (CLM) were obtained using Pluronic® F127 and its efficacy tested on the growth of four breast cancer cell lines. The impact of the CLM on the growth and functional hallmarks of breast CSCs were also evaluated using mammosphere and CSC reporter cell lines. Results: CLM improved the stability and growth inhibitory effects of citral. Importantly, CLM fully blocking the stemness features of CSCs (self-renewal, differentiation and migration) and in combination with paclitaxel CLM sensitized breast cancer cells to the chemotherapy. Conclusion: Targeting CSCs with CLM could improve the treatment of advanced breast cancer in combination with the standard chemotherapy.

Delivery of Cinnamic Aldehyde Antioxidant Response Activating nanoParticles (ARAPas) for Vascular Applications.

Selective delivery of nuclear factor erythroid 2-related factor 2 (Nrf2) activators to the injured vasculature at the time of vascular surgical intervention has the potential to attenuate oxidative stress and decrease vascular smooth muscle cell (VSMC) hyperproliferation and migration towards the inner vessel wall. To this end, we developed a nanoformulation of cinnamic aldehyde (CA), termed Antioxidant Response Activating nanoParticles (ARAPas), that can be readily loaded into macrophages ex vivo. The CA-ARAPas-macrophage system was used to study the effects of CA on VSMC in culture. CA was encapsulated into a pluronic micelle that was readily loaded into both murine and human macrophages. CA-ARAPas inhibits VSMC proliferation and migration, and activates Nrf2. Macrophage-mediated transfer of CA-ARAPas to VSMC is evident after 12 h, and Nrf2 activation is apparent after 24 h. This is the first report, to the best of our knowledge, of CA encapsulation in pluronic micelles for macrophage-mediated delivery studies. The results of this study highlight the feasibility of CA encapsulation and subsequent macrophage uptake for delivery of cargo into other pertinent cells, such as VSMC.

Dissolution behavior of Olmesartan Medoxomil drug in Polymeric Micelles of Soluplus and Pluronic F127

The aim of the present work was to study the dissolution behaviour of a poorly water-soluble Olmesartan Medoxomil (class II drug), by forming polymeric micelles (PMs) of SoluPlus and Pluronic F127. Polymeric Micelles of SoluPlus and Pluronic F127 were prepared by the co-solvent evaporation method. Drug and excipient compatibility study were carried out by Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry. The formulations were evaluated for particle size, Zeta Potential, Solubility studies, drug loading and encapsulation efficiency. Scanning Electron Microscopy (SEM) analysis was performed to study the surface morphology of the PMs. The SEM images showed spherical surface of the micelles. The drug loading efficiency was more for SoluPlus micelles compared to Pluronic F127 micelles. The Polymeric micelles showed negative zeta potential value indicating that they are stable and resist aggregation. The particle size was around 100nm and polydispersity index was less than 1 indicating uniform size distribution. The drug release from the SoluPlus micelles was higher than the Pluronic micelles. These results suggest that the polymeric micelles can be used to increase the solubility of poorly water-soluble drugs.

General Synthesis of Ultrafine Monodispersed Hybrid Nanoparticles from Highly Stable Monomicelles.

Ultrafine nanoparticles with organic-inorganic hybridization have essential roles in myriad applications. Over the past three decades, although various efforts on the formation of organic or inorganic ultrasmall nanoparticles have been made, ultrafine organic-inorganic hybrid nanoparticles have scarcely been achieved. Herein, a family of ultrasmall hybrid nanoparticles with a monodisperse, uniform size is synthesized by a facile thermo-kinetics-mediated copolymer monomicelle approach. These thermo-kinetics-mediated monomicelles with amphiphilic ABC triblock copolymers are structurally robust due to their solidified polystyrene core, endowing them with ultrahigh thermodynamic stability, which is difficult to achieve using Pluronic surfactant-based micelles (e.g., F127). This great stability combined with a core-shell-corona structure makes the monodispersed monomicelles a robust template for the precise synthesis of ultrasmall hybrid nanoparticles with a highly uniform size. As a demonstration, the obtained micelles/SiO2 hybrid nanoparticles display ultrafine sizes, excellent uniformity, monodispersity, and tunable structural parameters (diameters: 24-47 nm and thin shell thickness: 2.0-4.0 nm). Notably, this approach is universal for creating a variety of multifunctional ultrasmall hybrid nanostructures, involving organic/organic micelle/polymers (polydopamine) nanoparticles, organic/inorganic micelle/metal oxides (ZnO, TiO2 , Fe2 O3 ), micelle/hydroxides (Co(OH)2 ), micelle/noble metals (Ag), and micelle/TiO2 /SiO2 hybrid composites. As a proof of concept, the ultrasmall micelle/SiO2 hybrid nanoparticles demonstrate superior toughness as biomimetic materials.

Enhanced Skin Permeation of Punicalagin after Topical Application of Pluronic Micelles or Vesicles Loaded with Lafoensia pacari Extract.

Punicalagin, the principal ellagitannin of Lafoensia pacari leaves, has proven antioxidant activity, and standardized extracts of L.pacari can be topically used for skin aging management. We hypothesized that Pluronic nanomicelles or vesicles could solubilize sufficiently large amounts of the standardized extracts of L.pacari and provide chemical stability to punicalagin. The standardized extracts of L.pacari were obtained with an optimized extraction procedure, and the antioxidant activity was characterized. Formulations containing Pluronic at 25% and 35% were obtained with or without Span 80. They were characterized by average diameter, polydispersity index, punicalagin content, physicochemical stability, and rheology. A release and skin permeation study was carried out in vertical diffusion cells. The extraction procedure allowed quantifying high punicalagin content (i.e., 141.61 ± 3.87 mg/g). The standardized extracts of L.pacari showed antioxidant activity for all evaluated methods. Pluronic at 25 and Pluronic at 35 with standardized extracts of L.pacari showed an average diameter of about 25 nm. The addition of Span 80 significantly increased the mean diameter by 15-fold (p < 0.05), indicating the spontaneous formation of vesicles. Pluronic formulations significantly protected punicalagin from chemical degradation (p < 0.05). Pluronic at 25 formulations presented as free-flowing liquid-like systems, while Pluronic at 35 resulted in an increase of about 44-fold in |ƞ*|. The addition of Span 80 significantly reduced the Pluronic sol-gel transition temperature (p < 0.05), indicating the formation of vesicles. Formulations with Span 80 significantly enhanced punicalagin skin permeation compared to formulations without Span 80 (p < 0.05). Formulations with Span 80 were demonstrated to be the most promising formulations, as they allowed significant permeation of punicalagin (about 80 to 315 µg/cm2), which has been shown to have antioxidant activity.

Drug reformulation for a neglected disease. The NANOHAT project to develop a safer more effective sleeping sickness drug.

Human African trypanosomiasis (HAT or sleeping sickness) is caused by the parasite Trypanosoma brucei sspp. The disease has two stages, a haemolymphatic stage after the bite of an infected tsetse fly, followed by a central nervous system stage where the parasite penetrates the brain, causing death if untreated. Treatment is stage-specific, due to the blood-brain barrier, with less toxic drugs such as pentamidine used to treat stage 1. The objective of our research programme was to develop an intravenous formulation of pentamidine which increases CNS exposure by some 10-100 fold, leading to efficacy against a model of stage 2 HAT. This target candidate profile is in line with drugs for neglected diseases inititative recommendations. To do this, we evaluated the physicochemical and structural characteristics of formulations of pentamidine with Pluronic micelles (triblock-copolymers of polyethylene-oxide and polypropylene oxide), selected candidates for efficacy and toxicity evaluation in vitro, quantified pentamidine CNS delivery of a sub-set of formulations in vitro and in vivo, and progressed one pentamidine-Pluronic formulation for further evaluation using an in vivo single dose brain penetration study. Screening pentamidine against 40 CNS targets did not reveal any major neurotoxicity concerns, however, pentamidine had a high affinity for the imidazoline2 receptor. The reduction in insulin secretion in MIN6 β-cells by pentamidine may be secondary to pentamidine-mediated activation of β-cell imidazoline receptors and impairment of cell viability. Pluronic F68 (0.01%w/v)-pentamidine formulation had a similar inhibitory effect on insulin secretion as pentamidine alone and an additive trypanocidal effect in vitro. However, all Pluronics tested (P85, P105 and F68) did not significantly enhance brain exposure of pentamidine. These results are relevant to further developing block-copolymers as nanocarriers, improving BBB drug penetration and understanding the side effects of pentamidine.

Mechanistic insight into morphological transition of Pluronic aggregates in aqueous solution via tuning hydrogen bonding strength

Hydrogen bonding interaction has been increasingly recognized as a viable tool for manipulating the morphology of amphiphilic block copolymers aggregates in selective media. In this regard, mechanistic understanding on the impact of the strength of such an interaction on the morphological transition of the aggregates is of crucial importance for rational design targeting functional assemblies, yet still remains poorly understood. By performing multiple experimental techniques and molecular dynamics simulations (MDS), we here demonstrate how the morphology of Pluronic P123 micelles evolves by introduction of three octane derivatives (i.e., n-octanol, n-octylamine and n-octanoic acid) capable of forming distinct hydrogen bonding strength with P123 in aqueous solution. It is found that the P123-n-octanol mixture exhibits spherical aggregates as P123 alone. However, upon adding n-octylamine, the P123 micelles undergo sphere-short rod-long worm transition in both concentration and temperature-dependent manners. Interestingly, n-octanoic acid brings about a series of morphological transition from sphere, long worm to unilamellar vesicles as the concentration increases and the formed vesicles are fairly stable in the tested temperature range (20–60 °C). The nature of the additives acting on the copolymer aggregates was probed by 2D-NMR and MDS. Although both of the hydrophobic and hydrogen bonding interactions between the additives and block copolymers affect the architecture of the copolymer aggregates, the diverse strength of the latter generating from the functional groups (viz. –OH, –NH2 and –COOH) of the additives with the ether oxygen atoms on P123 backbone results in distinct location of the three additives in the micelles, consequently leading to varying micellar morphologies. This work enriches our knowledge of hydrogen bonding driven morphological transition of amphiphilic block copolymers aggregates, and as a result the fabrication of a desired nano-material through fine-tuning the hydrogen bonding strength can be straightforwardly envisaged.

Novel Cationic Meso-Arylporphyrins and Their Antiviral Activity against HSV-1.

This work is devoted to the search for new antiherpes simplex virus type 1 (HSV-1) drugs among synthetic tetrapyrroles and to an investigation of their antiviral properties under nonphotodynamic conditions. In this study, novel amphiphilic 5,10,15,20-tetrakis(4-(3-pyridyl-n-propanoyl)oxyphenyl)porphyrin tetrabromide (3a), 5,10,15,20-tetrakis(4-(6-pyridyl-n-hexanoyl)oxyphenyl)porphyrin tetrabromide (3b) and known 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetraiodide (TMePyP) were synthesized, and their dark antiviral activity in vitro against HSV-1 was studied. The influence of porphyrin’s nanosized delivery vehicles based on Pluronic F127 on anti-HSV-1 activity was estimated. All the received compounds 3a, 3b and TMePyP showed virucidal efficiency and had an effect on viral replication stages. The new compound 3b showed the highest antiviral activity, close to 100%, with the lowest concentration, while the maximum TMePyP activity was observed with a high concentration; porphyrin 3a was the least active. The inclusion of the synthesized compounds in Pluronic F-127 polymeric micelles had a noticeable effect on antiviral activity only at higher porphyrin concentrations. Action of the received compounds differs by influence on the early or later reproduction stages. While 3a and TMePyP acted on all stages of the viral replication cycle, porphyrin 3b inhibited viral replication during the early stages of infection. The resulting compounds are promising for the development of utilitarian antiviral agents and, possibly, medical antiviral drugs.