Estudo e desenvolvimento de lipossomas com potencial para aplicação em base cosmética

A acne vulgar é uma das doenças cutâneas mais comuns, apresentando como um de seus fatores fisiopatológicos primários a colonização pelo microrganismo Propionibacterium acnes. Atualmente, têm-se buscado terapias alternativas para o combate ao P. acnes, destacando-se alguns ácidos graxos, como o ácido laúrico (LA). O LA é uma molécula pouco solúvel em água, sendo possível sua incorporação em lipossomas. Os lipossomas apresentam capacidade de encapsulação/ liberação de ativos e impedem a desidratação da pele, tornando-se ingredientes inovadores na área de cosméticos. Foram preparados lipossomas de dipalmitoilfosfatidilcolina (DPPC) contendo diferentes concentrações de LA, que variaram de 0 a 50% da concentração total em mol, em quatro pHs: 9,0, 7,4, 5,0 e 3,0. Nestes pHs o estado de protonação do LA muda variando de 0 a -1. Os lipossomas foram extrusados por filtros com poros de 100 nm de diâmetro visando à obtenção de vesículas unilamelares grandes (LUV). As LUV foram caracterizadas quanto a sua estabilidade em condições de prateleira, temperatura de transição de fase da bicamada, encapsulamento no interior aquoso, liberação do LA, difusão das vesículas na pele e seus aspectos morfológicos foram caracterizados por espalhamento de raios-X a baixo ângulo (SAXS) e crio-microscopia eletrônica de transmissão. Estudos de estabilidade mostraram que independentemente da concentração de LA, as formulações são mais estáveis em pHs mais altos, quando LA está em sua maioria na forma de laurato. Os experimentos de DSC revelaram que em pHs 3,0 e 5,0 e concentrações maiores de LA, a interação deste ácido graxo com as bicamadas é favorecida, havendo um aumento da temperatura de transição de fase (Tm) e diminuição da cooperatividade. Análises de taxa de incorporação de sondas hidrofílicas confirmaram a presença de um compartimento aquoso interno para as vesículas de DPPC:LA. O LA conseguiu permear a pele no período avaliado e pouco LA foi liberado das vesículas em condições de temperatura ambiente. A morfologia das LUV se mostrou bem diferente da esperada e se observaram vesículas com mais de uma bicamada e outros formatos que não o esférico. Estes resultados podem auxiliar na otimização das condições para uma formulação que poderá ser usada no tratamento da acne, aumentando a eficácia do LA no sítio alvo.

Obtenção de gel mucoadesivo de nistatina para o tratamento da candidíase oral. Desenvolvimento e caracterização de dispersões sólidas de nistatina

A nistatina (NYS) é o fármaco de primeira escolha no tratamento da candidíase oral, que frequentemente acomete mais os indivíduos imunocomprometidos e pacientes com outras desordens (diabetes não tratada, neoplasias, imunodeficiências). No mercado brasileiro, a NYS é encontrada na forma de suspensão oral aquosa, onde o procedimento para sua administração consiste em bochechar o medicamento. Apesar de haver a indicação de que se mantenha o contato direto entre fármaco e a mucosa oral, na qual se encontra a Candida spp., o que aumentaria expressivamente o sucesso terapêutico, a suspensão não apresenta tal propriedade. Assim, a NYS que é fármaco com ação efetiva contra a candidíase oral, é considerada pertencente à Classe IV do Sistema de Classificação Biofarmacêutica, ou seja, apresenta baixa solubilidade e baixa permeabilidade. A baixa solubilidade pode comprometer sua disponibilidade na cavidade oral, e consequentemente, sua ação farmacológica. Diante desse quadro, o objetivo do presente trabalho foi o desenvolvimento de dispersões sólidas de NYS para o tratamento da candidíase oral, e sua posterior incorporação em gel mucoadesivo oral, favorecendo a formulação no local de ação. As dispersões sólidas são sistemas farmacêuticos, onde um fármaco pouco solúvel em água encontra-se dispersado em um carreador, no estado sólido. Os carreadores normalmente são hidrofílicos, o que permite que esses sistemas sejam empregados para aumentar a solubilidade aquosa do fármaco. Assim, foram desenvolvidas as dispersões sólidas de NYS, pelo método de eliminação do solvente, empregando como carreadores, lactose, HPMC, poloxamer 407 e poloxamer 188. Essas foram submetidas à caracterização por análise térmica, usando os ensaios de calorimetria exploratória diferencial (DSC) e termogravimetria/termogravimetria derivada (TG/DTG). Dentre essas dispersões sólidas, aquelas que se mostraram com comportamento térmico sugerindo a formação de um novo \"sistema\", foram analisadas por meio de ensaio de solubilidade. Dessa forma, a formulação NYS DS G2 (49) se destacou, pois apresentou maior solubilidade em água (4,484 mg/mL); em pH 5,5 (4,249 mg/mL) e em pH 7,0 (4,293 mg/mL), ou seja, houve um aumento de 1,426 vezes em água; 4,227 vezes em pH 5,5; e 2,743 vezes em pH 7,0. Essa formulação foi, por fim avaliada por difração de raio-X e espectroscopia de infravermelho com transformada de Fourier, técnicas que corroboraram com a análise térmica quanto à indicação de formação da dispersão sólida. Por sua vez, essa dispersão sólida foi incorporada em 4 bases de géis mucoadesivos de carbopol ® 934 PNF, alterando apenas a concentração do polímero (0,5; 1,0; 1,5; 2,0 %p/p). Foi observado que a liberação de NYS DS G2 (49) foi superior, quando comparada à liberação de NYS MP a partir do gel, e através do ensaio de mucoadesão, percebeu-se que os géis desenvolvidos apresentaram propriedades mucoadesivas compatíveis com relatos na literatura, independentemente da quantidade de carbopol ® empregada. As características reológicas foram distintas, e foi observado que as formulações Gel A e Gel B, que possuem menor quantidade de polímero, tiverem um indicativo de comportamento de fluido newtoniano, diferente dos demais, o que pode não ser desejado para esse tipo de forma farmacêutica tópica e semi-sólida. Ao final desse trabalho, pode-se concluir que foi possível desenvolver um sistema farmacêutico na forma de dispersão sólida com maior solubilidade que a NYS pura, e sua incorporação em uma forma farmacêutica mucoadesiva, e que a liberação da NYS na forma DS foi muito superior que o fármaco na forma \"convencional\", o que permite que a NYS esteja mais disponível na cavidade oral, e também junto à mucosa bucal, o que levaria a efeito farmacológico mais efetivo do antifúngico.

Bioactive compounds and physical and chemical characteristics of mini tomatoes: influence of postharvest treatments

Tomatoes are among the most cultivated and used vegetables in the world. They are very succeptible to post harvest losses due to high perishability, therefore the use of postharvest treatments may contribute to conservation of this fruit, however the treatments might affect significantly physico-chemical, sensory and nutritional characteristics of tomatoes. Given the perishability of tomato and the economic importance of small tomato fruits, the purpose of the present study was to determine the effect of gamma radiation, carnauba coating and 1-MCP treatments on tomato fruit quality during storage. The study may be divided into two parts. In the first, mini tomatoes cv. Sweet Grape were harvested at breaker stage, divided into 4 grous and treated with gamma radiation (0.6 kGy), carnauba coating (1 L 1000 kg-1) and 1-MCP (500 nL L-1) and then stored at 25±2°C for 30 days with a control group of tomatoes. In the seconnd part, tomatoes harvested at light-red stage were submitted to the same treatments and storage period. Every 6 days tomatoes were evaluated for color modifications, fruit firmness, souble and total pectin (only for light-red tomatoes), mass loss, titratable acidity (TA), soluble solids (SS), SS/TA ratio, carotenoids profile, formation of lycopene isomers, total phenolic compounds, ascorbic acid and antioxidant capacity. For tomatoes harvested at breaker stage and submitted to the treatments the results showed mass loss was delaying mainly by carnauba wax, and to a lesser extend by 1-MCP. Fruit firmness were better retained for 1-MCP treated fruits and carnauba treatment showed a transient effect in preserving fruit firmness. SS/TA of tomatoes treated with gamma radiation and carnauba presented no differences from control values, and were lower with the application of 1-MCP. Color was negatively affected by 1-MCP and earlier changed (6th day) when gamma radiation was applied. In relation to bioactive compounds of tomatoes harvest at breaker stage, results indicated gamma radiation and 1-MCP decreased the final content of lycopene and produced more (Z)-isomers of lycopene. Gamma radiation also induced a decreased in ?-carotene and an increased in phenolic compounds by the end of storage period. 1-MCP treatment promoted a slow down increase in ascorbic acid content during storage. Antioxidant capacity of the hydrophilic fraction was not dramatically affected by treatments and the lipophilic fraction was lower, especially for 1-MCP fruits. In addition, contents of ?-carotene, lycopene, (Z)-isomers of lycopene, ascorbic acid and antioxidant capacity increased during the period of storage while contents of lutein and phenolic compounds tended to decrease. Regarding tomatoes harvest at light-red stage, the most effective treatments for delaying fruit firmness and mass loss was carnauba and 1-MCP, while gamma radiation was the treatment with higher mass loss and the less fruit firmness, which could be associated with the higher solubilization of pectins promoted by radiation treatment. Color (L* and Hue) was mainly affected by 1-MCP treatment which delayed color development, however, by the end of storage, the values were not different from the other treatments. SS/TA ratio was lower for fruits treated with 1-MCP and TA was not so dramatically affected by treatments. Furthermore, mini tomatoes harvested at light-red stage, demonstrated irradiation induced changes in the final content of lycopene, increasing it, and formed less (13Z)-lycopene, while 1-MCP and carnauba coating slow down the increase in lycopene and slown down the decrease of ascorbic acid and phenolic compounds. Antioxidant capacity of lipophilic fraction was not affected by treatments and the hydrophilic fraction was lower for irradiated fruits only on day 0 as well as phenolic compounds. In the other days, no differences among treatments were observed for hydrophilic antioxidant capacity. Considering the results, the best combination of SS and TA and fruit preservation for mini tomatoes harvest at breaker stage was promoted by carnauba coating, which seems to be the treatment that causes fewer changes in bioactive compounds of breaker tomatoes. However, when mini tomatoes were harvested at light-red stage, SS/TA ratio and color were better and, to preserve the quality of these fruits, besides carnauba coating, 1-MCP also could be indicated

El Clot de Galvany-Balsares: clasificación y caracterización de zonas húmedas del litoral alicantino (SE España) mediante las metodologías RAC/SPA y MEDWET

Este trabajo es el segundo de una serie de estudios que se realizó para caracterizar las comunidades vegetales presentes en ambientes litorales en el SE de la provincia de Alicante, mediante el cartografiado de zonas homogéneas y el empleo de los catálogos propuestos por el RAC-SPA y Medwet. Se han determinado 11 unidades ambientales en el sector analizado que se corresponde al Clot de Galvany y Balsares, las cuales se han descrito y se han representado en 2 mapas que permite comparar las diferencias entre ambos catálogos. De este modo, se seleccionaron 10 parcelas al azar y su vegetación fue muestreada según la metodología, basada en transectos, denominada «quadrat technique» y se identificaron las diferentes especies vegetales en el campo. Por otro lado, la medida de la cobertura vegetal total también fue tomada según la metodología de «Braun Blanquet». Se han empleado los programas informáticos CartaLinx® y ArcView® para el cartografiado de las unidades vegetales. Así, la finalidad de este trabajo es proporcionar una serie de herramientas técnicas para poder garantizar la gestión sostenible de la compleja situación de la zona de estudio, así como de sus recursos naturales.

Conformational changes of dissolved humic and fulvic superstructures with progressive iron complexation

Conformational changes of a humic acid (HA) and a fulvic acid (FA) induced by iron complexation were followed by high-performance size exclusion chromatography (HPSEC) with both UV–vis and refractive index (RI) detectors. Molecular size distribution was reduced for HA and increased for FA with progressive iron complexation. Since interactions of Fe with humic components are electrostatic, it is likely that the triple-charged Fe ions formed stronger complexes with the more acidic hydrophilic and hydrated FA than with the less acidic and more hydrophobic HA. The large content of ionized carboxyl groups in FA, thus favored the formation of intra- or intermolecular bridges between the negatively charged fulvic acid molecules, and led to more compact and larger size network than for HA. Conversely, iron complexation with HA disrupted the humic conformational arrangements stabilized by only weak hydrophobic bonds into smaller-size aggregates of greater conformational stability due to formation of strong metal complexes. These results confirmed that humic molecules in solution were organized in supramolecular associations of relatively small molecules loosely bound together by dispersive interactions and hydrogen bonds, and they specifically responded to chemical changes brought about by metal additions. The present study revealed the molecular changes occurring in superstructures of natural organic matter when in metal complexes and contributed to understand and predict the environmental behavior in waters and soil of metal complexes with natural organic matter.

Fate and Transport of Naproxen in a Sandy Aquifer Material: Saturated Column Studies and Model Evaluation

Naproxen-C14H14O3 is a nonsteroidal anti-inflammatory drug which has been found at detectable concentrations in wastewater, surface water, and groundwater. Naproxen is relatively hydrophilic and is in anionic form at pH between 6 and 8. In this study, column experiments were performed using an unconsolidated aquifer material from an area near Barcelona (Spain) to assess transport and reaction mechanisms of Naproxen in the aquifer matrix under different pore water fluxes. Results were evaluated using HYDRUS-1D, which was used to estimate transport parameters. Batch sorption isotherms for Naproxen conformed with the linear model with a sorption coefficient of 0.42 (cm3 g−1), suggesting a low sorption affinity. Naproxen breakthrough curves (BTCs) measured in soil columns under steady-state, saturated water flow conditions displayed similar behavior, with no apparent hysteresis in sorption or dependence of retardation (R, 3.85-4.24) on pore water velocities. Soil sorption did not show any significant decrease for increasing flow rates, as observed from Naproxen recovery in the effluent. Sorption parameters estimated by the model suggest that Naproxen has a low sorption affinity to aquifer matrix. Most sorption of Naproxen occurred on the instantaneous sorption sites, with the kinetic sorption sites representing only about 10 to 40% of total sorption.

Paving the way for methane hydrate formation on metal–organic frameworks (MOFs)

The presence of a highly tunable porous structure and surface chemistry makes metal–organic framework (MOF) materials excellent candidates for artificial methane hydrate formation under mild temperature and pressure conditions (2 °C and 3–5 MPa). Experimental results using MOFs with a different pore structure and chemical nature (MIL-100 (Fe) and ZIF-8) clearly show that the water–framework interactions play a crucial role in defining the extent and nature of the gas hydrates formed. Whereas the hydrophobic MOF promotes methane hydrate formation with a high yield, the hydrophilic one does not. The formation of these methane hydrates on MOFs has been identified for the first time using inelastic neutron scattering (INS) and synchrotron X-ray powder diffraction (SXRPD). The results described in this work pave the way towards the design of new MOF structures able to promote artificial methane hydrate formation upon request (confined or non-confined) and under milder conditions than in nature.

Desiccant capability of organic xerogels: Surface chemistry vs porous texture

Resorcinol-Formaldehyde xerogels are organic polymers that can be easily tailored to have specific properties. These materials are composed of carbon, hydrogen and oxygen, and have a surface that is very rich in oxygen functionalities, and is therefore very hydrophilic. Their most interesting feature is that they may have the same chemical composition but a different porous texture. Consequently, the influence of porous characteristics, such as pore volume, surface area or pore size can be easily assessed. In this work, a commonly used desiccant, silica gel, is compared with organic xerogels to determine their rate and capacity of water adsorption, and to evaluate the role of surface chemistry versus porous texture. It was found that organic xerogels showed a higher rate of moisture adsorption than silica gel. Pore structure also seems to play an important role in water adsorption capacity. The OX-10 sample, whose porosity was mainly composed of micro-mesoporosity displayed a water adsorption capacity two times greater than that of the silica gel, and three times higher than that of the totally macroporous xerogel OX-2100. The presence of feeder pores (mesopores) that facilitate the access to the hydrophilic surface was observed to be the key factor for a good desiccant behaviour. Neither the total pore volume nor the high surface area (i.e. high microporosity) of the desiccant sample, is as important as the mesopore structure.

Polymerizable Peptide Monomers for the Targeted and Intracellular Delivery of Cancer Therapeutics

Thesis (Ph.D.)--University of Washington, 2016-06

The role of morphine-6-glucuronide (M6G) in pain control

Morphine-6beta-D-glucuronide (M6G) is an analgesically active metabolite of morphine, accounting for approximate to10% of the morphine dose when administered by systemic routes to humans. Although M6G is more hydrophilic than morphine, it crosses the blood-brain barrier, albeit relatively slowly. For this reason, it is generally thought that, after chronic dosing, M6G contributes significantly to the analgesic effects of systemically administered morphine. Owing to its polar nature, M6G is cleared from the systemic circulation primarily via renal elimination. As M6G accumulates in patients with renal impairment, there is an increased risk of M6G-induced respiratory depression in renal failure patients who are being dosed chronically with systemic morphine. Consistent with its analgesic and respiratory depressant properties, M6G binds to the p-opioid receptor in a naloxone-reversible manner. Although the affinity of M6G for the mu-opioid receptor is similar to or slightly less than that of morphine, preclinical studies in rodents show that M6G is one to two orders of magnitude more potent than morphine when administered by central routes. This major discrepancy between the markedly higher intrinsic antinociceptive potency of M6G relative to morphine, despite their similar p-opioid receptor binding affinities, is difficult to reconcile. It has been proposed that M6G mediates its pain-relieving effects through a novel 'M6G opioid receptor', while others have argued that M6G may have higher efficacy than morphine for transduction of intracellular events. When administered by parenteral routes to rodents, M6G's antinociceptive potency is no more than twofold higher than morphine. In humans, the analgesic efficacy and respiratory depressant potency of M6G relative to morphine have been assessed in a number of short-term studies involving the intrathecal or intravenous routes of administration. For example, in hip replacement patients, intrathecal M6G provided excellent postoperative analgesia but the occurrence of late respiratory depression in 10% of these patients raised serious concern about safety. In postoperative patients, intravenous M6G administered by means of patient-controlled analgesia (PCA), or bolus plus PCA, produced no analgesia in one study and limited analgesia in another. Similarly, there was a lack of significant analgesia in healthy volunteers who received intravenous M6G for the alleviation of experimental pain (carbon dioxide applied to the nasal mucosa). In contrast, satisfactory analgesia was produced by bolus doses of intravenous M6G administered to patients with cancer pain, and to healthy volunteers with experimentally-induced ischaemic, electrical or thermal (ice water) pain. Studies to date in healthy volunteers suggest that intravenous M6G may be a less potent respiratory depressant and have a lower propensity for producing nausea and vomiting than morphine. However, it is unclear whether equi-analgesic doses of M6G and morphine were compared. Clearly, more extensive short-term trials, together with studies involving chronic M6G administration, are necessary before the potential clinical utility of M6G as an analgesic drug in its own right can be determined.

Fatty acids as haptens: exploring the limits of antigenicity

Fatty acids (FAs) are relatively small, hydrophobic and highly mobile molecular structures with vital biological functions and a ubiquitous distribution. Surprisingly, however, they can be rendered immunogenic. We have synthesised a novel immunogen in which dicarboxylic linoleic acid was conjugated to a carrier protein. Dicarboxylic fatty acids (DCA) differ from their normal counterparts only by their possession of a carboxyl group at each end of the molecule. When conjugated to proteins as haptens, they are, therefore, presented to the immune system with a free carboxyl group at the distal end, instead of a methyl group. Polyclonal IgG antibodies raised in response to this unique immunogen could bind not only conjugated hapten with high affinity, but also the equivalent free FA in mono and dicarboxylic form. Similar conjugates constructed from normal FAs produced much weaker antibody responses and could scarcely be considered antigenic at all. The cross-reactivities of the anti-DCA antibodies with FA variants differing in the number, position and configuration of their double bonds showed that the antibody paratope (binding site) was structured to accommodate the hapten in a way that depended on the precise shape of the acyl chain. We suggest that FAs become much more effective as B-cell epitopes when presented with their hydrophilic carboxyl group exposed on the surface of immunogenic conjugates. This type of epitope is determined by the particular double bond pattern of the unsaturated acyl chain, as well as the polar head group. (C) 2003 Elsevier Ltd. All rights reserved.

In vitro bioactivity of MOEP grafted ePTFE membranes for craniofacial applications

The bioactivity of three methacryloyloxyethyl phosphate (MOEP) grafted expanded polytetrafluoroethylene (ePTFE) membranes with varying surface coverage as well as unmodified ePTFE was investigated through a series of in vitro tests: calcium phosphate (CaP) growth in simulated body fluid (SBF), serum protein adsorption, and a morphology and attachment study of human osteoblast-like SaOS-2 cells. The graft copolymers were prepared by means of gamma irradiation induced grafting and displayed various surface morphologies and wettabilities depending on the grafting conditions used. Unmodified ePTFE did not induce nucleation of Cal? minerals, whereas all the grafted membranes revealed the growth of Cal? minerals after 7 days immersion in SBF. The sample with lowest surface grafting yield (24% coverage), a smooth graft morphology and relatively high hydrophobicity (theta(adv) = 120 degrees, theta(rec) = 80 degrees) showed carbonated hydroxyapatite growth covering the surface. On the other hand, the samples with high surface grafting yield (76% and 100%), a globular graft morphology and hydrophilic surfaces (theta(adv) = 60 degrees and 80 degrees, theta(rec) = 25 degrees and 15 degrees, respectively) exhibited irregular growth of non-apatitic Cap minerals. Irreversibly adsorbed protein measured after a 1 h immersion in serum solution was quantified by the amount of nitrogen on the surface using XPS, as well as by weight increase. All grafted membranes adsorbed 3-6 times more protein than the unmodified membrane. The sample with the highest surface coverage adsorbed the most protein. Osteoblast-like SaOS-2 cells cultured for 3 h revealed significantly higher levels of cell attachment on all grafted membranes compared to unmodified ePTFE. Although the morphology of the cells was heterogeneous, in general, the higher grafted surfaces showed a much better cell morphology than both the low surface-grafted and the control unmodified sample. The suite of in vitro tests confirms that a judicious choice of grafted monomer such as the phosphate-containing methacrylate monomer (MOEP) significantly improves the bioactivity of ePTFE in vitro. (c) 2005 Elsevier Ltd. All rights reserved.

Gastrointestinal absorption of Heparin by lipidization or coadministration with penetration enhancers

A review with 93 references. Heparins are high molecular weight, hydrophilic polyanions, which are unstable under acidic conditions; and therefore they exhibit poor oral bioavailability. Consequently they must be administered via the parenteral route which is expensive, inconvenient, and limits use by outpatients. The development of an oral form of heparin is warranted. This review examined the literature, mostly published between January 2000 and January 2005, pertaining to the gastrointestinal absorption of heparin by lipidization or coadministration with penetration enhancers. A lipidization strategy that was examined involved conjugation of low molecular weight heparin with deoxycholic acid. The majority of studies examined the ability of different formulations, typically utilizing penetration enhancers, to improve heparin bioavailability. The penetration enhancers used included fatty acids, Labrasol™, Gelucire 44/14™, polycationic lipophilic-core dendrons, saponins, mono-N-carboxymethyl chitosan, Carbopol® 934P, a combination of thiolated polycarbophil and glutathione, polymeric nanoparticles, polymeric microparticles, sodium N-[8-(2-hydroxybenzoyl) amino]caprylate (SNAC), and sodium N-[10-(2-hydroxybenzoyl)amino]decanoate (SNAD). The variety of models used and doses of heparin/penetration enhancers applied, however, made it difficult to compare the results between studies. Nevertheless, all of the reviewed drug delivery systems showed therapeutic value and confirmation of the promising results obtained from animal studies, by progression to clinical trials, is necessary. Overall, progress has been made in the quest for an oral heparin formulation.

The structure of ultrathin Langmuir-Blodgett films of cadmium behenate

Grazing incidence x-ray-diffraction investigations of the structures of Langmuir-Blodgett films of cadmium behenate with 1, 2, 3, 5, and 21 monolayers are reported. The single monolayer film, deposited on a hydrophilic substrate, showed a hexagonal structure, whereas the bilayer film, deposited on a hydrophobic substrate, had a rectangular structure with herringbone orientation of the acyl chains. With multilayer films formed on a hydrophilic substrate, it was possible to detect that the hexagonal structure of the first layer was retained when additional layers were deposited and that the additional layers had the same rectangular structure as the bilayer. (c) 2005 American Institute of Physics.

Synthesis of gadolinium-labeled shell-crosslinked nanoparticles for magnetic resonance imaging applications

Shell-crosslinked knedel-like nanoparticles (SCKs; knedel is a Polish term for dumplings) were derivatized with gadolinium Shell chelates and studied as robust magnetic-resonance-imaging-active structures with hydrodynamic diameters of 40 +/- 3 nm. SCKs possessing an amphiphilic core-shell morphology were produced from the aqueous assembly of diblock copolymers of poly(acrylic acid) (PAA) and poly(methyl acrylate) (PMA), PAA(52)-b-PMA(128), and subsequent covalent crosslinking by amidation upon reaction with 2,2'-(ethylenedioxy)bis(ethylamine) throughout the shell layer. The properties of these materials, including non-toxicity towards mammalian cells, non-immunogenicity within mice, and capability for polyvalent targeting, make them ideal candidates for utilization within biological systems. The synthesis of SCKs derivatized with Gd-III and designed for potential use as a unique nanometer-scale contrast agent for MRI applications is described herein. Utilization of an amino-functionalized diethylenetriaminepentaacetic acid-Gd analogue allowed for direct covalent conjugation throughout the hydrophilic shell layer of the SCKs and served to increase the rotational correlation lifetime of the Gd. In addition, the highly hydrated nature of the shell layer in which the Gd was located allowed for rapid water exchange; thus, the resulting material demonstrated large ionic relaxivities (39 s(-1) mM(-1)) in an applied magnetic field of 0.47 T at 40 degrees C and, as a result of the large loading capacity of the material, also demonstrated high molecular relaxivities (20 000 s(-1) mM(-1)).