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Poly[2-(dimethylamino)ethyl methacrylate-b-2-methacryloyloxyethyl phosphorylcholine] (DMA-MPC) is currently under investigation as a new vector candidate for gene therapy. The DMA block has been previously demonstrated to condense DNA effectively. The MPC block contains a phosphorylcholine (PC) headgroup, which can be found naturally in the outside of the cell membrane. This PC-based polymer is extremely hydrophilic and acts as a biocompatible steric stabilizer. In this study, we assess in detail the morphologies of DNA complexes obtained using the diblock copolymer series DMAxMPC30 (where the mean degree of polymerization of the MPC block was fixed at 30 and the DMA block length was systematically varied) using transmission electron microscopy (TEM) and liquid atomic force microscopy (AFM). Both techniques indicate more compact complex morphologies (more efficient condensation) as the length of the cationic DMA block increases. However, the detailed morphologies of the DMAxMPC30−DNA complexes observed by TEM in vacuo and by AFM in aqueous medium are different. This phenomena is believed to be related to the highly hydrophilic nature of the MPC block. TEM studies revealed that the morphology of the complexes changes from loosely condensed structures to highly condensed rods, toroids, and oval-shaped particles as the DMA moiety increases. In contrast, morphological changes from plectonemic loops to flowerlike and rectangular blocklike structures, with an increase in highly condensed central regions, are observed by in situ AFM studies. The relative population of each structure is clearly dependent on the polymer molecular composition. Enzymatic degradation assays revealed that only the DMA homopolymer provided effective DNA protection against DNase I degradation, while other highly condensed copolymer complexes, as judged from TEM and gel electrophoresis, only partially protected the DNA. However, AFM images indicated that the same highly condensed complexes have less condensed regions, which we believe to be the initiation sites for enzymatic attack. This indicates that the open structures observed by AFM of the DNA complexation by the DMAxMPC30 copolymer series are closer to in vivo morphology when compared to TEM.

Nonviral gene delivery systems based on DNA complexes with polycations have recently been extensively studied. An important consideration in the design of such therapeutic systems is the understanding of forces governing the DNA−polycation interaction and the complex stabilization. In this work, the interaction of a cationic polymer from the poly(amidoamine) family (poly(bis-acryloylpiperazine-2-methyl-piperazine), p(BAP-2MP)) with DNA at different salt concentrations and pHs and in different buffers was studied using isothermal titration microcalorimetry as a principal tool. The binding isotherms were analyzed using a proposed complexation−condensation model, to calculate the observed binding constant, Kobs, enthalpies of the complex formation and condensation process, %@mt;sys@%Δ%@ital@%H%@rsf@%%@/xs;55;%lnwidth@%°%@/xs;63;(%lnwidth-x55)@%%@mh;-x63@%%@sb@%com%@sbx@%%@mx@% and %@mt;sys@%Δ%@ital@%H%@rsf@%%@/xs;55;%lnwidth@%°%@/xs;63;(%lnwidth-x55)@%%@mh;-x63@%%@sb@%con%@sbx@%%@mx@% , and complexation site and condensation site exclusion sizes, ncom and ncon, respectively. Kobs, %@mt;sys@%Δ%@ital@%H%@rsf@%%@/xs;55;%lnwidth@%°%@/xs;63;(%lnwidth-x55)@%%@mh;-x63@%%@sb@%com%@sbx@%%@mx@% , and %@mt;sys@%Δ%@ital@%H%@rsf@%%@/xs;55;%lnwidth@%°%@/xs;63;(%lnwidth-x55)@%%@mh;-x63@%%@sb@%con%@sbx@%%@mx@% decreased with increasing salt concentration, indicating involvement of electrostatic interactions. However, ncom was rather independent of salt concentration and nearly equal to the average number of ionized charges at the polycation, indicating that the ratio of nucleotide to p(BAP-2MP) monomer units is close to 1. Dissection of the free energy of interaction showed that electrostatic contributions dominate the p(BAP-2MP)−DNA interaction. The use of buffers with different protonation enthalpies demonstrated that the p(BAP-2MP) interaction with DNA is coupled with a proton extraction from the buffer resulting in an enthalpy change and enabling the polymer ionization and interaction at a stoichiometric ratio. Obtained intrinsic binding parameters (in a buffer with ΔHion = 0) reveal that p(BAP-2MP) interaction with DNA is nonspecific with a moderate binding constant and that it contains the enthalpic contribution (probably due to the formation of hydrogen bonding). The values for the condensation process, ncon and %@mt;sys@%Δ%@ital@%H%@rsf@%%@/xs;55;%lnwidth@%°%@/xs;63;(%lnwidth-x55)@%%@mh;-x63@%%@sb@%con%@sbx@%%@mx@% , indicate that there is no further ionization of the p(BAP-2MP) polymer to interact with DNA and that the stoichiometric ratio is preserved.

Nonviral gene delivery systems based on DNA complexes with polycations have recently been extensively studied. An important consideration in the design of such therapeutic systems is the understanding of forces governing the DNA−polycation interaction and the complex stabilization. In this work, the interaction of a cationic polymer from the poly(amidoamine) family (poly(bis-acryloylpiperazine-2-methyl-piperazine), p(BAP-2MP)) with DNA at different salt concentrations and pHs and in different buffers was studied using isothermal titration microcalorimetry as a principal tool. The binding isotherms were analyzed using a proposed complexation−condensation model, to calculate the observed binding constant, Kobs, enthalpies of the complex formation and condensation process, %@mt;sys@%Δ%@ital@%H%@rsf@%%@/xs;55;%lnwidth@%°%@/xs;63;(%lnwidth-x55)@%%@mh;-x63@%%@sb@%com%@sbx@%%@mx@% and %@mt;sys@%Δ%@ital@%H%@rsf@%%@/xs;55;%lnwidth@%°%@/xs;63;(%lnwidth-x55)@%%@mh;-x63@%%@sb@%con%@sbx@%%@mx@% , and complexation site and condensation site exclusion sizes, ncom and ncon, respectively. Kobs, %@mt;sys@%Δ%@ital@%H%@rsf@%%@/xs;55;%lnwidth@%°%@/xs;63;(%lnwidth-x55)@%%@mh;-x63@%%@sb@%com%@sbx@%%@mx@% , and %@mt;sys@%Δ%@ital@%H%@rsf@%%@/xs;55;%lnwidth@%°%@/xs;63;(%lnwidth-x55)@%%@mh;-x63@%%@sb@%con%@sbx@%%@mx@% decreased with increasing salt concentration, indicating involvement of electrostatic interactions. However, ncom was rather independent of salt concentration and nearly equal to the average number of ionized charges at the polycation, indicating that the ratio of nucleotide to p(BAP-2MP) monomer units is close to 1. Dissection of the free energy of interaction showed that electrostatic contributions dominate the p(BAP-2MP)−DNA interaction. The use of buffers with different protonation enthalpies demonstrated that the p(BAP-2MP) interaction with DNA is coupled with a proton extraction from the buffer resulting in an enthalpy change and enabling the polymer ionization and interaction at a stoichiometric ratio. Obtained intrinsic binding parameters (in a buffer with ΔHion = 0) reveal that p(BAP-2MP) interaction with DNA is nonspecific with a moderate binding constant and that it contains the enthalpic contribution (probably due to the formation of hydrogen bonding). The values for the condensation process, ncon and %@mt;sys@%Δ%@ital@%H%@rsf@%%@/xs;55;%lnwidth@%°%@/xs;63;(%lnwidth-x55)@%%@mh;-x63@%%@sb@%con%@sbx@%%@mx@% , indicate that there is no further ionization of the p(BAP-2MP) polymer to interact with DNA and that the stoichiometric ratio is preserved.

Small-angle neutron scattering (SANS) has been used to study the internal structure of poly(lactic acid)−poly(ethylene glycol) (PLA(d)−PEG) block copolymer assemblies, which are being investigated as particulate drug carriers. Three PLA(d)−PEG copolymers with a fixed PEG of 5 kDa and a fully deuterated PLA(d) block of either 3, 15, or 45 kDa were synthesized by the ring opening polymerization of d8-d,l-lactide, using stannous octoate as a catalyst. These copolymers assembled to form nanoparticles in aqueous media, following precipitation from a water miscible organic solvent. The hydrodynamic radius of the PLA(d)−PEG nanoparticles increased with the molecular weight of the PLA(d) block. SANS data obtained at three different solvent contrasts were analyzed simultaneously using core−shell models, which assumed a homogeneous core of uniform scattering length density and a simple functional form for the scattering length density profile of the shell. The thickness and structure of the stabilizing PEG layer were found to depend on the molecular weight of the PLA(d) block. The splayed PEG chains of the PLA(d)−PEG 3:5 assemblies were characteristic of those found in polymeric micelles. However, as the molecular weight of the PLA(d) block was increased, the PEG brush became more radially homogeneous, in accord with recent Scheutjens−Fleer mean-field theory predictions.

The optimization of DNA−cationic polymer complexation is crucial for nonviral gene delivery. Although physicochemical characterization of the interaction between DNA and cationic polymers has recently attracted more attention in the nonviral DNA delivery field, the literature on the effect of varying polycation charge density on DNA−cationic polymer complexation is still scarce. Thus, the aim of this study was to systematically assess the influence of the degree of ionization of a weak cationic polyelectrolyte (poly[2-(dimethylamino)ethyl methacrylate] or DMAEMA homopolymer) on its ability to form complexes with DNA. This was achieved by varying the solution pH from 4.0 to 8.0 and analyzing the resulting effects on the binding affinity, thermodynamic properties, complex size, and morphology. Lowering the solution pH led to higher degrees of ionization for the cationic polymer and hence greater binding affinities with DNA, as judged by the increased propensity of the former to displace ethidium bromide from DNA and also by relatively low monomer:nucleotide molar ratio (0.8:1) required to retard the migration of free DNA. Isothermal titration microcalorimetry studies further confirmed that a stronger interaction occurred at low pH than at high pH. By decreasing the pH from 8.0 to 6.6, Kobs increased from 7.8 × 10⁵ to 20.4 × 10⁵ M^-1. More efficient condensation at low pH was demonstrated by the reduction of ethidium bromide fluorescence in the loading wells from gel electrophoresis, decreased complex sizes without agglomeration occurring at high polymer/DNA ratios, together with discrete and dense spherical complexes observed in TEM studies. This may be attributed to the presence of electrostatic stabilization from excess cationic polymer chains, which provide a repulsive shell around the polymer/DNA complex. The physicochemical data indicate that the increased degree of ionization for the DMAEMA homopolymer at lower pH results in higher binding affinity, smaller and more compact complexes, and more efficient condensation. These findings therefore highlight the importance of the degree of ionization on DNA complex formation for weak cationic polyelectrolytes.

A series of poly(lactic acid)−poly(ethylene oxide) (PLA−PEG) AB block copolymers have been synthesized and used to produce aqueous dispersions of micellar-like nanoparticles. The hydrodynamic radius of the PLA core plus the stabilizing 5 kDa PEG layer, as determined by photon correlation spectroscopy, increased with the molecular weight of the PLA block. PLA−PEG particles have possible application as drug carriers for targeted drug delivery. In addition to particle size, the layer thickness and mobility of the hydrated PEG chains will be important in determining the particle's ability to avoid uptake by the defense system of the body, the phagocytic cells of the reticuloendothelial system. Viscoelastic measurements were used to investigate interparticle interactions in concentrated dispersions of the PLA−PEG nanoparticles. This approach has not previously been used to study how the interactions in dispersions of micellar-like assemblies depend on the copolymer geometry. When the volume fraction of the dispersions, φcore, was increased, the storage modulus, G‘, became greater than the loss modulus, G‘ ‘, indicating steric interaction between the PEG chains. At higher φcore values, compression of the grafted polymer chains was observed. The critical volume fraction at which overlap of the PEG chains commences, φcore^crit (i.e., G‘ = G‘ ‘), was used in conjunction with the overall hydrodynamic radius to determine the grafted PEG chain layer thickness. Micellar-like nanoparticles assembled from a PLA−PEG copolymer with a 5 kDa PEG block and a relatively low molecular weight 3 kDa PLA chain had an appreciable steric layer thickness of 6.3 nm. Hence, interparticle interactions in the concentrated dispersion were “soft” in nature as a result of the long-range interactions, as shown by the weak scaling dependence of the storage modulus on the volume fraction. The layer became more extended as the molecular weight of the PLA block was increased from 3 to 6 kDa, and as a consequence the PEG chains became less compressible. By using this method to characterize the PEG layer, it should be possible to rationalize the in vivo performance of the PLA−PEG nanoparticles and therefore aid the design of particulate drug carriers.

Star-shaped poly(ethylene glycol)-block-polyethylenimine [star-(PEG-b-PEI)] significantly enhance plasmid DNA condensation of low molecular weight (MW) PEIs. The star-block copolymers were prepared via a facile synthesis route using hexamethylene diisocyanate as linker between PEG and PEI blocks. NMR and FT-IR spectroscopy confirmed the structures of intermediately activated PEG and final products. Furthermore, the copolymers were characterized by size exclusion chromatography, static light scattering, and viscosimetry. Their molecular weights (Mw 19−26 kDa) were similar to high MW PEI (25 kDa). Thermoanalytical investigations (thermogravimetric analysis, differential scanning calorimetry) were also performed and verified successful copolymer synthesis. DNA condensation with the low MW PEIs (800 and 2000 Da) and their 4- and 8-star-block copolymers was studied using atomic force microscopy, dynamic light scattering, zeta-potential measurements, and ethidium bromide (EtBr) exclusion assay. It was found that low MW PEIs formed huge aggregates (500 nm to 2 μm) in which DNA is only loosely condensed. By contrast, the star-block copolymers yielded small (80−110 nm), spherical and compact complexes that were stable against aggregation even at high ionic strength and charge neutrality. Furthermore, as revealed in the EtBr exclusion assay these star-block copolymers exhibited a DNA condensation potential as high as high MW PEI. Since these star-(PEG-block-PEI) copolymers are composed of relatively nontoxic low MW PEI and biocompatible PEG, their potential as gene delivery agents merits further investigations.

For two series of polyethylenimine-graft-poly(ethylene glycol) (PEI-g-PEG) block copolymers, the influence of copolymer structure on DNA complexation was investigated and physicochemical properties of these complexes were compared with the results of blood compatibility, cytotoxicity, and transfection activity assays. In the first series, PEI (25 kDa) was grafted to different degrees of substitution with PEG (5 kDa) and in the second series the molecular weight (MW) of PEG was varied (550 Da to 20 kDa). Using atomic force microscopy, we found that the copolymer block structure strongly influenced the DNA complex size and morphology:  PEG 5 kDa significantly reduced the diameter of the spherical complexes from 142 ± 59 to 61 ± 28 nm. With increasing degree of PEG grafting, complexation of DNA was impeded and complexes lost their spherical shape. Copolymers with PEG 20 kDa yielded small, compact complexes with DNA (51 ± 23 nm) whereas copolymers with PEG 550 Da resulted in large and diffuse structures (130 ± 60 nm). The ζ-potential of complexes was reduced with increasing degree of PEG grafting if MW ≥ 5 kDa. PEG 550 Da did not shield positive charges of PEI sufficiently leading to hemolysis and erythrocyte aggregation. Cytotoxicity (lactate dehydrogenase assay) was independent of MW of PEG but affected by the degree of PEG substitution:  all copolymers with more than six PEG blocks formed DNA complexes of low toxicity. Finally, transfection efficiency of the complexes was studied. The combination of large particles, low toxicity, and high positive surface charge as in the case of copolymers with many PEG 550 Da blocks proved to be most efficient for in vitro gene transfer. To conclude, the degree of PEGylation and the MW of PEG were found to strongly influence DNA condensation of PEI and therefore also affect the biological activity of the PEI-g-PEG/DNA complexes. These results provide a basis for the rational design of block copolymer gene delivery systems.

NMR studies on a series of poly(lactic acid)−poly(ethylene oxide) (PLA−PEG) diblock copolymers have been carried out in d6-acetone and in D2O. Nanoparticles of the PLA−PEG copolymers were obtained using a modified interfacial polymer deposition−solvent evaporation technique (Fessi, H.; Devissaguet, J. P.; Puisieux, F.; Thies, C. French Patent 2 608 988, 1986). In D2O, the PLA block forms a central hydrophobic core, while the PEG block forms an hydrophilic corona layer. In D2O, the hydrophobic core of the nanoparticle is generally not seen, while the PEG corona is observed. Only the PLA methyl protons at the interface between the two regions are observed, and these are seen as a double doublet structure. For nanoparticles with a low molecular weight PLA block length, an additional methyl multiplet signal is seen suggesting that PLA methyl groups are in more than one chemical environment. This is not seen for nanoparticles with a high molecular weight PLA block length indicating more uniform structure in the core interfacial region. As temperature is increased, the core of the latter becomes more liquidlike. Quantitative calibration studies of the PEG corona layer show that most of the PEG layer is seen indicating that it is in the liquid phase and on the surface of the nanoparticle. ¹³C solid-state NMR spectroscopy studies indicate the presence of a central solidlike core and a more mobile interfacial region at the PLA−PEG interface, while the relaxation rate of the nanoparticle obtained from T1 studies indicates that the PEG corona is a much more mobile environment than the interfacial methyl protons.

The micellar-like particle systems produced from poly-D,L-lactide-poly(ethylene glycol) (PLA-PEG) copolymers have been assessed using a range of physicochemical characterisation methods, followed by in vivostudies of their biodistribution after intravenous administration to the rat. The size of the PEG chain was kept constant at 5 or 2 kDa, while the PLA size increased within a series from 2 to 25 kDa. The results obtained reveal, that in an aqueous medium the copolymers assembled into micellar-like structures, with the PLA segments forming the core and the PEG segments the surrounding corona. The size of the PLA segments dominated the process of assembly of the molecules and the characteristics of the resultant micellar-like particles. The PLA-PEG micellar particles were found to be less dynamic than those obtained from conventional surfactants. Particles formed from the lower molecular weight PLA polymers allowed a level of chain mobility while the cores of the micellar particles formed from higher molecular weight PLA appeared to be solid-like in nature. The size of the micellar particles was dependent on the copolymer molecular weight and the z-average diameter increased from 25 to 76 nm as the molecular weight of the PLA moiety increased. This provides an ability to control the particle size by adjusting the molecular weight of the PLA moiety. Following intravenous administration to the rat model, micellar-like particles smaller than approximately 70 nm accumulated in the liver, despite the fact that the PEG corona provided an effective steric stabilization effect. Micellar-like particles with a diameter of more than approximately 70 nm exhibited prolonged systemic circulation and reduced liver uptake, although the steric stabilisation of these particles was shown to be less effective. These findings agree with recent observations from other research groups; that indicate a possibility that very small particulates can pass through the sinusoidal fenestrations in the liver and gain access to the parenchymal cells of the liver.

Nanoparticles assembled from poly(d,l-lactic acid)−poly(ethylene glycol) (PLA−PEG) block copolymers may have a therapeutic application in site-specific drug delivery. A series of AB block copolymers based on a fixed PEG block (5 kDa) and a varying PLA segment (2−110 kDa) have been synthesized by the ring-opening polymerization of d,l-lactide using stannous octoate as a catalyst. These copolymers assembled to form spherical nanoparticles in aqueous media following precipitation from a water-miscible organic solvent. ¹H NMR studies of the PLA−PEG nanoparticles in D2O confirmed their core−shell structure, with negligible penetration of the hydrated PEG chains into the PLA core. The influence of the PLA block molecular weight on the hydrodynamic size and micellar aggregation number of the assemblies was determined by dynamic and static light scattering techniques. The hydrodynamic radius of the PLA−PEG 2:5−30:5 nanoparticles was solely dependent on the copolymer architecture and scaled linearly as NPLA^1/3, where NPLA is the number of monomeric units in the PLA block. The PEG chains of the small PLA−PEG 2:5 and 3:5 assemblies appeared to be fairly splayed as a consequence of their relatively low aggregation number and high surface coverage. However, as NPLA was increased to 6 kDa the area available per PEG chain at the periphery of the shell decreased significantly and then remained fairly constant with further increases in the molecular weight of the PLA block. The aggregation number and hence particle size of nanoparticles produced from copolymers with a PLA block of 45 kDa or more was found to also depend on the concentration of copolymer dissolved in the organic phase during preparation. This suggested that that the PEG chains had little influence on the assembly of the higher molecular weight copolymers.

The morphology of condensates formed between plasmid DNA and a PEG−poly(amidoamine) triblock copolymer were investigated using TEM and AFM in aqueous conditions. Both techniques revealed the presence of ring and extended linear structures; however, a greater proportion of linear structures was obtained with the PEG copolymer than was seen with the poly(amidoamine) homopolymer, indicating that the PEG was interfering with condensation. Differences in the ring diameters between the PEG copolymer and the homopolymer were more marked with TEM than AFM, suggesting that compact toroidal structures are largely due to constriction on dehydration and that this is prevented from occurring in the presence of PEG. AFM revealed an increase in condensate size with increasing polymer/DNA ratio, which can be attributed to the association of more polymer with the complex. With TEM, the proportion of linear structures increased with increasing polymer/DNA ratio, whereas it remained relatively constant for AFM across all ratios. It is suggested that an increased amount of PEG associated with the complexes promotes disruption of the ring structure upon dehydration. This supports the hypothesis that rings are formed via the bending of linear structures, with an equilibrium existing between the two, that is altered in favor of the linear structure by PEG.

Dynamic real time assembly of toroidal and rod‐like DNA condensates has been visualised using atomic force microscopy. Imaging has been conducted in an aqueous environment allowing the visualisation of hydrated, pegylated‐polymer DNA condensates undergoing dynamic structural movement and conformational change. A major hurdle in the field of gene delivery is cellular transfection and the subsequent transfer of condensed genetic material to the cell nucleus. An increased understanding of the process of DNA condensation will aid the development and optimisation of gene delivery vectors.

The development of biomaterials to treat, repair, or reconstruct the human body is an increasingly important component of materials research. Collaboration between materials researchers and their industrial and clinical partners is essential for the development of this complex field. To demonstrate the importance of these interactions, two articles in this issue focus on advances in biomaterials relating to the use of colloidal systems for transport, drug delivery, and other medical applications. These articles were coordinated by Dominique Muster (Université Louis Pasteur, Strasbourg) and Franz Burny (Hôpital Erasme, Brussels). The following is the second of these two articles.

The in vitro degradation of nanospheres perpared from three benzyl ester derivatives of poly (ß-malic acid) containing 80, 90 and 100% of benzylated malic acid units was studied. The progressive decrease in the molecular weight of the copolymers was observed as the nanospheres degraded, demonstrating that the degradation under the experimental conditions occurred by a simple hydrolytic cleavage of the ester bond between the monomeric units. The degradation was slow, with the weight average molecular weight decreasing to about 70% of the initial value in 5 months for all the nanosphere systems. A comparison of degradation rates for benzyl ester copolymers with the degradation rate of poly (ß-malic acid) homopolymer demonstrated a decreased degradation rate of benzylated copolymers which suggests that the introduction of a pendent benzyl ester function in proximity to the ester bond in the main chain, reduces the rate of the bond cleavage. No significant difference in the degradation behaviour of highly benzylated copolymers, containing 90 and 80% of benzylated malic acid units, and fully benzylated polymer could be detected to prove an autocatalytic role on degradation of the free pendent carboxyl group in the former two copolymers.

Purpose. To investigate the effects of the modification of the copolymers poloxamer 407 and poloxamine 908 on the physical and biological properties surface modified polystyrene nanospheres. Methods. A method to modify poloxamer 407 and poloxamine 908, introducing a terminal amine group to each PEO chain has been developed. The aminated copolymers can be subsequently radiolabelled with lodinated (I125) Bolton-Hunter reagent. The aminated copolymers were used to surface modify polystyrene nanospheres. The physical and biological properties of the coated nanospheres were studied using particle size, zeta potential, in vitronon-parenchymal cell uptake and in vivobiodistribution experiments. Results. The presence of protonated amine groups in the modified copolymers significantly affected the physical and biological properties of the resulting nanospheres, although the effects were copolymer specific. The protonated surface amine groups in both copolymers reduced the negative zeta potential of the nanospheres. Acetylation of the copolymer's free amine groups resulted in the production of nanospheres with comparable physical properties to control unmodified copolymer coated nanospheres. In vivo, the protonated amine groups in the copolymers increased the removal of the nanospheres by the liver and spleen, although these effects were more pronounced with the modified poloxamer 407 coated nanospheres. Acetylation of the amine groups improved the blood circulation time of the nanospheres providing modified poloxamine 908 coated nanospheres with comparable biological properties to control poloxamine 908 coated nanospheres. Similarly, modified poloxamer 407 coated nanospheres had only slightly reduced circulation times in comparison to control nanospheres. Conclusions. The experiments have demonstrated the importance of copolymer structure on the biological properties of surface modified nanospheres. Modified copolymers, which possess comparable properties to their unmodified forms, could be used in nanosphere systems where antibody fragments can be attached to the copolymers, thereby producing nanospheres which target to specific body sites.

The adsorption of some selected poly(ethylene oxide) containing copolymers onto a model colloidal drug carrier (polystyrene latex) was studied in terms of the adsorption isotherm and hydrodynamic thickness of the coating layer. The copolymers were selected on the basis of the biological effects that they produce when adsorbed onto polystyrene latex. Investigated were two tetrafunctional block copolymers of poly(ethylene oxide)-poly(propylene oxide) ethylene diamine (Poloxamine 908 and Poloxamine 904), and ABA triblock copolymer of poly(ethylene oxide)-poly(propylene oxide) (Poloxamer 407) and two AB polylactide-poly(ethylene glycol) copolymers (PLA:PEG) with ratios of 1.5:2 and 2:5 of polylactide to the poly(ethylene glycol) moiety. The dimensions of the poly(ethylene oxide) (PEO) chains on the surface (the PEO layer thickness and the surface area per one PEO chain) are found to be similar for the copolymers with relatively high ratio of PEO to hydrophobic moiety and with similar PEO size (Poloxamine 908, Poloxamer 407 and PLA:PEG 2:5), irrespective of the differences in the copolymer molecular composition and structure. A comparison between the dimensions of PEO free in a solution and in the adsorbed layer (the PEO layer thickness) of these polymers reveals that the most probable conformation of the higher molecular weight PEO chains at the surface is an elongated coil. A comparison of the biological performances of these systems shows a dramatically different in-vivo behaviour of the systems with significantly different dimensions of the adsorbed PEO (Poloxamine 908 and 904), while those with the similar PEO dimensions may exhibit comparable biological properties (Poloxamer 407 and Poloxamine 908) despite difference in the polymer molecular structure.