Dynamic and static light scattering studies on self-aggregation behavior of biodegradable amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) triblock copolymers in aqueous solution

The self-aggregation behavior of two amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) (PEO-PHB-PEO) triblock copolymer samples with nearly identical PHB block lengths but different PEO block lengths, PEO-PHB-PEO(2000-810-2000) and PEO-PHB-PEO(5000-780-5000), was studied with dynamic and static light scattering (DLS and SLS), in combination with fluorescence spectroscopy and transmission electron microscopy (TEM). The formation of polymeric micelles by the two PEO-PHB-PEO triblock copolymers was confirmed with fluorescence technique and TEM. DLS analysis showed that the hydrodynamic radius (R(h)) of the monodistributed polymeric micelles increased with an increase in PEO block length. The relative thermostability of the triblock copolymer micelles was studied by SLS and DLS at different temperatures. The aggregation number and the ratio of the radius of gyration over hydrodynamic radius were found to be independent of temperature, probably due to the strong hydrophobicity of the PHB block. The combination of DLS and SLS studies indicated that the polymeric micelles were composed of a densely packed core of hydrophobic PHB blocks and a corona shell formed by hydrophilic PEO blocks. The aggregation numbers were found to be approximately 53 for PEO-PHB-PEO(2000-810-2000) micelles and approximately 37 for PEO-PHB-PEO(5000-780-5000) micelles. The morphology of PEO-PHB-PEO spherical micelles determined by DLS and SLS measurements was further confirmed by TEM.     

Specific interactions improve the loading capacity of block copolymer micelles in aqueous media

Block copolymer micelles find application in many fields as nanocarriers, especially in drug delivery. We report herein that specific interactions between hydrophobic guest molecules and core-forming segments can significantly improve the loading capacity of polymeric micelles. High loading capacities (>100% weight/weight of polymer (w/wp)) were systematically observed for the encapsulation of probes containing weak carboxylic acid groups by micellar nanoparticles having poly[2-(dialkylamino)ethyl methacrylate] cores (i.e., particles whose cargo space exhibits antagonist weak base functions), as demonstrated by the incorporation of indomethacin (IND), ibuprofen (IBPF), and trans-3,5-bis(trifluoromethyl)cinnamic acid (F-CIN) into either poly(ethylene oxide)-b-poly[2-(diisopropylamino)ethyl methacrylate] (PEO-b-PDPA) or poly(glycerol monomethacrylate)-b-PDPA (PG2MA-b-PDPA) micelles. The esterification of IND yielding to a nonionizable IND ethyl ester derivative (IND-Et) caused an abrupt decrease in the micellar loading capacity down to 10-15% w/wp. Similar results were also obtained when IND was combined with nonionizable block copolymers such as PEO-b-polycaprolactone (PEO-b-PCL) and PEO-b-poly(glycidyl methacrylate) (PEO-b-PGMA). The existence of acid-base interactions between the solubilizate and the weak polybase block forming the micelle core was confirmed by 1H NMR measurements. However, the incorporation of high numbers of hydrophobic guest molecules inside polymeric micelles can provoke not only an increase in the hydrodynamic size (2RH) of the objects but also a substantial change in the morphology (transition from spheres to cylinders). The application of the Higuchi model showed that the probe release followed a diffusion-controlled mechanism, and diffusion coefficients (D) on the order of 10-18-10-17 cm2/s were determined for IND release from 1.0 mg/mL PEO113-b-PDPA50 + 100% w/wp IND. Probe release from micelles with weak polybase-based cores can also be triggered by changes in the solution pH.     

Star-block copolymers as templates for the preparation of stable gold nanoparticles

Gold nanoparticles of improved stability against aggregation were prepared using poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) star-block copolymers. A five-arm star-shaped macroinitiator (PEO) was utilized for the automated parallel controlled ring-opening polymerization of epsilon-caprolactone to prepare a series of PEO-b-PCL star-block copolymers with a constant PEO core linked to PCL blocks of variable length. The PEO core was swelled with KAuCl4 in N,N-dimethylformamide (DMF), and gold nanoparticles were subsequently obtained by reduction with NaBH4. Since the process was always templated by the same PEO core for all investigated polymers, the average dimension of the formed gold nanoparticles was in the same range for all star-block copolymers. In sharp contrast, the size distribution and long-term stability against aggregation of the gold nanoparticles dispersed in DMF were strongly dependent on the PCL block length, confirming the role of PCL blocks as stabilizing blocks for these nanoparticles.     

Micelle or polymersome formation by PCL-PEG-PCL copolymers as drug delivery systems

Polymeric micelles and polymersomes may have great potential as the drug delivery vehicles for solubilization of hydrophobic drugs.     

Synthesis and pH-dependent micellization of diblock copolymer mixtures

This work focused on the preparation and the aqueous solution properties of hybrid polymeric micelles consisting of a hydrophobic poly(epsilon-caprolactone) (PCL) core and a mixed shell of hydrophilic poly(ethylene oxide) (PEO) and pH-sensitive poly(2-vinylpyridine) (P2VP). The hybrid micelles were successfully prepared by the rapid addition of acidic water to a binary solution of PCL(34)-b-PEO(114) and PCL(32)-b-P2VP(52) diblock copolymers in N,N-dimethylformamide. These micelles were pH-responsive as result of the pH-dependent ionization of the P2VP block. The impact of pH on the self-assembly of the binary mixture of diblocks-thus on the composition, shape, size and surface properties of the micelles-was studied by a variety of experimental techniques, i.e., dynamic and static light scattering, transmission electron microscopy, Zeta potential, fluorescence spectroscopy and complement hemolytic 50 test.     

Diblock copolymer micelles deliver hydrophobic protoporphyrin IX for photodynamic therapy

Polymeric micelles are emerging as an effective drug delivery system for hydrophobic photosensitizers in photodynamic therapy (PDT). The objective of this study was to investigate the formulation of hydrophobic protoporphyrin IX (PpIX) with MePEG(5000)-b-PCL(4100) [methoxy poly (ethylene glycol)-b-poly (caprolactone)] diblock copolymers and to compare their PDT response to that of free PpIX. The photophysical and photochemical properties of the polymeric PpIX micelles were studied by measuring absorbance and fluorescence spectra, PpIX-loading efficiency and stability, the micelle particle size and morphology, as well as singlet oxygen luminescence and lifetime. The spherical micelles have a high PpIX-loading efficiency of 82.4% and a narrow size distribution with a mean diameter of 52.2 +/- 6.4 nm. The cellular uptake of PpIX in RIF-1 cells using PpIX micelles was approximately two-fold higher than that for free PpIX. Free PpIX and PpIX formulated in micelles exhibited similar subcellular localization in or around the cellular plasma membrane, as demonstrated using fluorescence microscopy. In vitro PDT results showed that the PpIX micelles have markedly increased photocytotoxicity over that with free PpIX, by nearly an order of magnitude at the highest light dose used. The micelles alone had no evident phototoxicity or dark toxicity. These findings suggest that MePEG(5000)-b-PCL(4100) diblock copolymer micelles have great potential as a drug delivery system for hydrophobic photodynamic sensitizers.     

Adsorption of poly(ethylene oxide)-b-poly(epsilon-caprolactone) copolymers at the silica-water interface

The adsorption of amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) and poly(ethylene oxide)-b-poly(gamma-methyl-epsilon-caprolactone) copolymers in aqueous solution on silica and glass surfaces has been investigated by flow microcalorimetry, small-angle neutron scattering (SANS), surface forces, and complementary techniques. The studied copolymers consist of a poly(ethylene oxide) (PEO) block of M(n) = 5000 and a hydrophobic polyester block of poly(epsilon-caprolactone) (PCL) or poly(gamma-methyl-epsilon-caprolactone) (PMCL) of M(n) in the 950-2200 range. Compared to homoPEO, the adsorption of the copolymers is significantly increased by the connection of PEO to an aliphatic polyester block. According to calorimetric experiments, the copolymers interact with the surface mainly through the hydrophilic block. At low surface coverage, the PEO block interacts with the surface such that both PEO and PCL chains are exposed to the aqueous solution. At high surface coverage, a dense copolymer layer is observed with the PEO blocks oriented toward the solution. The structure of the copolymer layer has been analyzed by neutron scattering using the contrast matching technique and by tapping mode atomic force microscopy. The experimental observations agree with the coadsorption of micelles and free copolymer chains at the interface.     

The Effect of the Hydrophilic/Hydrophobic Ratio of Polymeric Micelles on their Endocytosis Pathways into Cells

Fluorescein isothiocyanate (FITC), a fluorescent probe, is coupled to amphiphilic monomethoxy poly(ethylene glycol)‐block‐poly(ε‐caprolactone) (mPEG‐PCL) copolymers. FITC‐labeled mPEG‐PCL copolymers self‐assemble into micelles through the solvent evaporation method. The cellular internalization is examined using fluorescence microscopy on incubation of NIH‐3T3 fibroblasts with micelles or free FITC solution. The effect of the hydrophilic/hydrophobic ratio on the endocytosis mechanisms is evaluated by fluorescence microscopy on culturing of human hepatoblastoma cells and human umbilical vein endothelial cells, individually, mixed with the micelles holding the same parameters including micelle size, shape, and surface charges.

     

Langmuir and Langmuir-Blodgett films of poly(ethylene oxide)-b-poly(epsilon-caprolactone) star-shaped block copolymers

Self-assembly of poly(ethylene oxide)-block-poly(epsilon-caprolactone) five-arm stars (PEO-b-PCL) was studied at the air/water (A/W) interface. The block copolymers consist of a hydrophilic PEO core with hydrophobic PCL chains at the star periphery. All the polymers have the same number of ethylene oxide repeat units (9 per arm), and the number of epsilon-caprolactone repeat units ranges from 0 to 18 per arm. The Langmuir monolayers were analyzed by surface pressure/mean molecular area isotherms, compression-expansion hysteresis experiments, and isobaric relaxation measurements, and the Langmuir-Blodgett (LB) films' morphologies were investigated by atomic force microscopy (AFM). PCL homopolymers crystallize directly at the A/W interface in a narrow surface pressure range (11-15 mN/m). In the same pressure region, the star-shaped block copolymers undergo a phase transition corresponding to the collapse and the crystallization of the PCL chains as shown by the presence of a pseudoplateau in the isotherms. The LB films were prepared by transferring the Langmuir monolayers onto mica substrates at various surface pressures. AFM imaging confirmed the formation of PCL crystals in the LB monolayers of the PCL homopolymers and of the copolymers, but also showed that the PCL segments can undergo additional crystallization after monolayer transfer during water evaporation. The PCL crystal morphologies were also strongly influenced by the surface pressure and by the PEO segments.     

Asymmetrical flow field-flow fractionation with multi-angle light scattering and quasi elastic light scattering for characterization of poly(ethyleneglycol-b-ɛ-caprolactone) block copolymer self-assemblies used as drug carriers for photodynamic therapy

Poly(ethyleneoxide-b-?-caprolactone) (PEO-b-PCL) self-assemblies in water were characterized by asymmetrical flow field-flow fractionation (AsFlFFF), with on-line coupling with quasi-elastic light scattering (QELS), multi-angle light scattering (MALS), refractive index and UV/Vis detection. We report here the AsFlFFF analysis of three different nanoparticular self-assembled systems of PEO-PCL polymers in aqueous media, each polymer differing by the mass of the PEO and PCL fragments. Thus, self-assembled water samples of {PEO(2000)-b-PCL(2600)}, {PEO(5000)-b-PCL(1400)} and {PEO(5000)-b-PCL(4000)} were analyzed by AsFlFFF. In most cases, the size obtained by AsFlFFF was similar to the one characterized by DLS. However, in some instances, only AsFlFFF revealed the presence of several self-assemblies with very different sizes. These nanoparticles being used for the targeted delivery of photosensitizers in photodynamic therapy, it was important to fully characterize the samples in terms of size and size distribution, molecular weight, Ip, aggregation number and also to assess whether the photosensitizer was inside the nanoparticles. AsFlFFF proved to be a very efficient technique which enabled this study without any destruction of the nanoparticles.     

Synthesis,characterization, and properties of amphiphilic chitosan copolymers with mixed side chains by click chemistry

Novel amphiphilic chitosan copolymers with mixed side chains of poly(ε‐caprolactone) and poly(ethylene oxide) (CS‐g‐PCL/PEO) were successfully synthesized by “graft to” approach via click chemistry. The melting and crystallization behaviors and crystalline morphology of CS‐g‐PCL/PEO copolymers can be adjusted by the alteration of the feed ratio of PCL and PEO segments. CS‐g‐PCL/PEO copolymers revealed crystalline morphology different from that of linear alkynyl PCL and alkynyl PEO due to the influence of brush structure of copolymers and the mutual influence of PCL and PEO segments. The hydrophilicity of the CS copolymers can be improved and adjusted by the alteration of the composition of PCL and PEO segments. Moreover, the CS copolymers can self‐assemble into spherical micelles in aqueous solution. Investigation shows that the size of the CS copolymer micelles increased with the increase of the content of hydrophobic PCL segments in copolymers, which indicated that the micellar behavior of the copolymers can be controlled by the adjustment of the ratio of PCL and PEO segments in copolymer. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3476–3486, 2010     

Two-dimensional self-assembly of linear poly(ethylene oxide)-b-poly(epsilon-caprolactone) copolymers at the air-water interface

The interfacial properties of amphiphilic linear diblock copolymers based on poly(ethylene oxide) and poly(epsilon-caprolactone) (PEO-b-PCL) were studied at the air-water (A/W) interface by surface pressure measurements (isotherms and hysteresis experiments). The resulting Langmuir monolayers were transferred onto mica substrates and the Langmuir-Blodgett (LB) film morphologies were investigated by atomic force microscopy (AFM). All block copolymers had the same PEO segment (Mn = 2670 g/mol) and different PCL chain lengths (Mn = 1270; 2110; 3110 and 4010 g/mol). Isothermal characterization of the block copolymer samples indicated the presence of three distinct phase transitions around 6.5, 10.5, and 13.5 mN/m. The phase transitions at 6.5 and 13.5 mN/m correspond to the dissolution of the PEO segments in the water subphase and crystallization of the PCL blocks above the interface similarly as for the corresponding homopolymers, respectively. The phase transition at 10.5 mN/m was not observed for the homopolymers alone or for their blends and arises from a brush formation of the PEO segments anchored underneath the adsorbed hydrophobic PCL segments. AFM analysis confirmed the presence of PCL crystals in the LB films with unusual hairlike/needlelike architectures significantly different from those obtained for PCL homopolymers.     

聚肽接枝共聚物的自组装行为研究

Polymeric micelles of poly(γ-benzyl L-glutamate)(PBLG)-poly(ethylene oxide)(PEO) graft copolymer were prepared by the dialysis method in deionized water. Fluorescence spectroscopy, nuclear magnetic resonance(NMR) and transmission electron microscope(TEM) were used for the investigation of the self-assembly of PBLG-PEO graft copolymer. Fluorescence spectrosco0y measurements suggest that PBLG-PEO graft copolymer associates to form polymeric micelles in water. ^1H NMR measurements further prove that in aqueous medium PBLG-PEO graft copolymer could assemble into polymeric micelles with PBLG segments as the hydrophobic inner core and PEO segments as the hydrophilic shell. The results of the TEM observations show that the polymeric micelles of PBLG-PEO graft copolymer are almost spindly shaped, which are different from the morphology of the spherical micelles formed by PBLG-PEO block copolymer. Polymeric micelles formed by polypeptide copolymer have potential application as drug carrier in controlled-release delivery system.     

Highly stable core-surface-crosslinked nanoparticles as cisplatin carriers for cancer chemotherapy

Cisplatin is a potent anticancer drug with low solubility in water. A new type of highly stable polymer micelles, namely core-surface-crosslinked nanoparticles (SCNPs) made from amphiphilic brush copolymers, were evaluated as the carrier of cisplatin. Cisplatin could be loaded in the SCNPs with poly(varepsilon-caprolactone) (PCL) cores and hydrophilic poly(ethylene glycol) (PEG) or poly[2-(N,N-dimethylamino)ethyl methacrylate] (PDMA) shells with high loading efficiency (approximately 90%). In vitro cellular uptake experiments indicated that both SCNPs could be easily taken up by SKOV-3 ovarian cancer cells. Both cell proliferation assay and IC50 measurements indicated that cisplatin encapsulated in the SCNPs had much enhanced cytotoxicity to the cancer cells compared to free cisplatin. The positive charges on the PCL/PDMA SCNPs promoted the cellular internalization of the nanoparticles, resulting in higher cytotoxicity of cisplatin in these SCNPs. The IC50 of the cisplatin encapsulated in PCL/PDMA SCNPs was as low as 0.01 microg/mL, lower than that of cisplatin in PCL/PEG SCNPs and free cisplatin.     

Cell–Membrane Penetration of Tat‐Conjugated Polymeric Micelles: Effect of Tat Coating Density

Considerable efforts have been devoted to enhancing the cell penetration of nanoparticles by coating cell‐penetrating peptides (CPPs) on the surface. However, the internalization mechanism for a CPP at different concentrations varies a lot. It is acknowledged that the mechanism is restricted to endocytic pathway at relatively low concentrations; however, direct translocation becomes dominant at high concentrations. This raises an interesting question on how the surface Tat coating density of the nanoparticles would influence their cell–membrane interaction and the consequent internalization behavior. This study systematically investigates the effect of Tat peptides on the internalization behavior of polymeric micelles by tuning surface Tat coating density, incubation concentrations, incubation time, and other factors using poly(ethylene glycol)–poly(ε‐caprolactone) copolymer (PEG‐PCL) micelles. It is found that both energy‐dependent and energy‐independent pathways are involved in the cellular uptake process, and the Tat‐conjugated polymeric micelles strongly accumulated on the cell surface at initial stage. The membrane‐anchoring and internalization rate increase with the increasing Tat coating density. Furthermore, the increasing of Tat coating density accelerates the energy‐independent pathway. It is envisioned that this finding will further shed light on the surface modification of nanoparticles for enhanced cell penetration and direct translocation into cell cytoplasm.     

Fluorescent micelles based on star amphiphilic copolymer with a porphyrin core for bioimaging and drug delivery

Star-shaped poly(ε-caprolactone)-b-poly(ethylene oxide) amphiphilic copolymer with a tetrakis-(4-aminophenyl)-terminated porphyrin core was synthesized. Paclitaxel (PTX)-loaded polymeric micelles were prepared by the self-assembly of the star copolymer and in situ encapsulation of PTX. The fluorescent characteristic of the porphyrin moiety allowed the cellular uptake and biodistribution of the PTX-loaded micelles to be monitored by fluorescent imaging. The PTX-loaded micelles can be readily internalized by cancer cells and have a slightly higher cytotoxicity than clinic PTX injection Taxol. In vivo real-time fluorescent imaging revealed that the micelles could accumulate at tumor site via the blood circulation in tumor-bearing mice. In vivo antitumor efficacy examinations indicated that the PTX-loaded micelles had significantly superior efficacy in impeding tumor growth than Taxol and low toxicity to the living mice.     

两亲性壳聚糖衍生物的制备及其包覆量子点

以天然壳聚糖为功能性高分子的骨架,通过西弗碱还原法,以正辛醛和端醛基聚乙二醇单甲基醚(mPEG aldehyde,mPEG-ald)修饰壳聚糖,制备了具有亲疏水性质的N-辛基化-N-mPEG化壳聚糖衍生物(N-octyl-N-mPEG-chitosan,OPEGC),并且以此两亲性壳聚糖衍生物包覆量子点制备了水溶性聚合物量子点纳米粒子.用FTIR、1H-NMR对壳聚糖衍生物进行了结构表征.制备的水溶性胶束,用动态光散射(DLS)测试其流体力学直径与分布,研究了烷基链接枝比率对粒径大小的影响,研究结果表明:烷基链接枝率越高,聚合物胶束粒径越小.以芘为分子探针,通过荧光光谱法测定了壳聚糖衍生物的临界胶束浓度(CMC)为2.032×10-2mg/mL,并对水溶性聚合物量子点纳米粒子进行了紫外、荧光及形貌表征,结果表明得到了荧光发射产率高的聚合物量子点纳米粒子,且尺寸均一、水溶性好.     

Monolayer-protected gold nanoparticles by the self-assembly of micellar poly(ethylene oxide)-b-poly(epsilon-caprolactone) block copolymer

A study is presented of the preparation of gold nanoparticles incorporated into biodegradable micelles. Poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) copolymer was synthesized by ring-opening polymerization, and the hydroxyl end group of the PCL block was modified with thioctic acid using dicyclohexyl carbodiimide as the coupling reagent. The PEO-b-PCL-thioctate ester (TE) thus obtained was used in a later step to form monolayer protected gold nanoparticles via the thioctate spacer. Gold nanoparticles stabilized with the PEO-b-PCL block (named Au/Block (x/y), where x/y is the mole feed ratio between HAuCl4 and PEO-b-PCL-TE) were prepared and analyzed. Au/Block (1/1), Au/Block (2/1), and Au/Block (3/1) nanoparticles were found to form stable dispersions in the organic solvents commonly used to dissolve the unlabeled block copolymer. The average diameter of the nanoparticles was determined by transmission electron microscopy (TEM) and found to be 6+/-2 nm. Au/Block (4/1) nanoparticle dispersions in organic solvents, on the other hand, were not stable and produced large gold clusters (50-100 nm). Cluster formation was attributed to the low grafting density of the block copolymer, which facilitates agglomeration. For Au/Block (12/1), along the same trend, only an insoluble product was isolated. Micelles in water were prepared by the slow addition of the dilute Au/Block solution in dimethylformamide into a large excess of water with vigorous stirring. Au/Block (1/1) and Au/Block (2/1) formed nanosized structures of 5-7 nm. TEM images of stained Au/Block (1/1) micelles, made in water, clearly showed the formation of core-shell structures. Au/Block (3/1) micelles, on the other hand, were not stable and large agglomerates a few microns in size were observed. The study focuses on the synthesis, characterization, and aggregation behavior of gold-loaded PEO-b-PCL block copolymer micelles, a potential system for drug delivery in conjunction with tissue and subcellular localization studies.     

Drug and plasmid DNA co-delivery nanocarriers based on abctype polypeptide hybrid miktoarm star copolymers

We report on the fabrication of self-assembled micelles from ABC-type miktoarm star polypeptide hybrid copolymers consisting of poly(ethylene oxide), poly(L-lysine), and poly(ε-caprolactone) arms, PEO(-b-PLL)-b-PCL, and their functional applications as co-delivery nanocarriers of chemotherapeutic drugs and plasmid DNA. Miktoarm star copolymer precursors, PEO(-b-PZLL)-b-PCL, were synthesized at first via the combination of consecutive "click" reactions and ring-opening polymerizations (ROP), where PZLL is poly(ε-benzyloxycarbonyl-L-lysine). Subsequently, the deprotection of PZLL arm afforded amphiphilic miktoarm star copolymers, PEO(-b-PLL)-b-PCL. In aqueous media at pH 7.4, PEO(-b-PLL)-b-PCL self-assembles into micelles consisting of PCL cores and hydrophilic PEO/PLL hybrid coronas. The hydrophobic micellar cores can effectively encapsulate model hydrophobic anticancer drug, paclitaxel; whereas positively charged PLL arms within mixed micellar corona are capable of forming electrostatic polyplexes with negatively charged plasmid DNA (pDNA) at N/P ratios higher than ca. 2. Thus, PEO(-b-PLL)-b-PCL micelles can act as co-delivery nanovehicles for both chemotherapeutic drugs and genes. Furthermore, polyplexes of pDNA with paclitaxel-loaded PEO(-b-PLL)-b-PCL micelles exhibited improved transfection efficiency compared to that of pDNA/blank micelles. We expect that the reported strategy of varying chain topologies for the fabrication of co-delivery polymeric nanocarriers can be further applied to integrate with other advantageous functions such as targeting, imaging, and diagnostics.     

Poly(ethylene glycol)-b-poly(epsilon-caprolactone) and PEG-phospholipid form stable mixed micelles in aqueous media

Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG(5000)-b-PCL(x)) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy poly(ethylene glycol) (PEG-DSPE), possess small size and high thermodynamic stability, raising their potential as long circulating carriers in the context of delivery of antineoplastic and antibiotic drugs. Formation of mixed polymeric micelles was confirmed using size exclusion chromatography and 1H NMR NOESY. Steady-state fluorescence measurements revealed depressed critical micellar concentrations indicative of a cooperative interaction between component hydrophobic blocks, which was quantified using the pseudophase model for micellization. Steady-state fluorescence measurements indicated that the mixed polymeric micelle cores possess intermediate micropolarity and high microviscosity. Pulsed field gradient spin-echo measurements were used to characterize micellar diffusion coefficients, which agree well with those obtained using dynamic light scattering. NOE spectra suggested that the hydrophobic polymer segments from individual components are in close proximity, giving evidence for the formation of a relatively homogeneous core. Contrary to one-component PEG(5000)-b-PCL(x) micelles, the mixed polymeric micelles could incorporate clinically relevant levels of the poorly water soluble antibiotic, amphotericin B (AmB). AmB encapsulation and release studies revealed an interesting composition-dependent interaction of the drug with the mixed polymeric micelle core.