Suprarrenalectomía larascópica single port / Single port laparoscopic adrenalectomy

Introducción: La Suprarrenalectomía quirúrgica es el tratamiento de elección en lesiones tumorales de la glándula suprarrenal mayores de 4 cm o aquellos que resulten funcionales. La técnica laparoscópica esta asociada a menor sangrado, morbilidad perioperatoria y estadía hospitalaria. El apoyo del abordaje single-port (LESS) se asocia además a menor dolor y mejores resultados estéticos, pero conlleva a una mayor complejidad técnica, sin embargo esta dificultad puede ser eliminada con el apoyo robótico, conservando los beneficios de la técnica single port.(AU)

Introduction: Surgical adrenalectomy is the treatment of choice in tumors of the adrenal gland larger than 4 cm or those that are functional. The laparoscopic technique is associated with less bleeding, perioperative morbidity and hospital stay. The support of the single-port approach (LESS) is also associated with less pain and better aesthetic results, but it leads to greater technical complexity, however this difficulty can be eliminated with robotic support, while retaining the benefits of the single port technique.

Synthetic peptides for the immunodiagnosis of hepatitis A virus infection.

VP1, VP2 and VP3 molecules of hepatitis A virus are exposed capsid proteins that have shown to be antigenic and are used for diagnosis in recombinant-antigen commercial kits. In this study, we developed a sequence analysis in order to predict diagnostic peptide epitopes, followed by their spot synthesis on functionalized cellulose paper (Pepscan). This paper with synthetic peptides was tested against a sera pool of hepatitis A patients. Two peptide sequences, that have shown an antigenic recognition, were selected for greater scale synthesis on resin. A dimeric form of one of these peptides (IMT-1996), located in the C-Terminus region of protein VP1, was antigenic with a recognition frequency of 87-100% of anti-IgG antibodies and 100% of anti-IgM antibodies employing the immunological assays MABA and ELISA. We propose peptide IMT-1996, with less than twenty residues, as a cheaper alternative for prevalence studies and diagnosis of hepatitis A infection.

Design and application of multifunctional DNA nanocarriers for therapeutic delivery.

The unique programmability of nucleic acids offers versatility and flexibility in the creation of self-assembled DNA nanostructures. To date, many three-dimensional DNA architectures of varying sizes and shapes have been precisely formed. Their biocompatibility, biodegradability and high intrinsic stability in physiological environments emphasize their emerging use as carriers for drug and gene delivery. Furthermore, DNA nanocarriers have been shown to enter cells efficiently and without the aid of transfection reagents. A key strength of DNA nanocarriers over other delivery systems is their modularity and their ability to control the spatial distribution of cargoes and ligands. Optimizing DNA nanocarrier properties to dictate their localization, uptake and intracellular trafficking is also possible. This review presents design considerations for DNA nanocarriers and examples of their use in the context of therapeutic delivery applications. The assembly of DNA nanocarriers and approaches for loading and releasing cargo are described. The stability and safety of DNA nanocarriers are also discussed, with particular attention to the in vivo physiological environment. Mechanisms of cellular uptake and intracellular trafficking are examined, and the paper concludes with strategies to enhance the delivery efficiency of DNA nanocarriers.

Evaluation of a lateral flow assay for the diagnosis of Mycobacterium bovis infection in dairy cattle.

A commercially available multi-antigen lateral flow assay (LFA) for detection of antibodies to Mycobacterium bovis was evaluated by testing dairy cattle in Baja California, México. Sera and tissue samples were obtained from 268 dairy cattle at a slaughterhouse and were tested by LFA, bacteriological culture, and polymerase chain reaction (PCR). Of 107 culture positive samples, 70 (65.4%) were positive by PCR and 49 (45.8%) were positive by LFA. The PCR and LFA gave positive results with an additional 59 (36.6%) and 77 (47.8%) of the 161 culture negative samples, respectively. The false negative rate for the PCR was 34.6% and 54.2% for the LFA. Due to the high false positive rate for both PCR and LFA observed in this study, the LFA cannot be a useful test, even in combination with PCR.

Detection of the Sm31 antigen in sera of Schistosoma mansoni- infected patients from a low endemic area.

Schistosoma mansoni cathepsin B (Sm31) is a major antigen from adult worms that circulates in the blood of infected patients (Li et al., Parasitol Res 1996; 82: 14-18). An analysis of the Sm31 sequence (Klinkert et al., Mol Biochem Parasitol 1989; 33: 113-122) allowed the prediction of seven hydrophilic regions that were confirmed to be exposed on the surface of a 3D model of Sm31; the species specificity of these regions was checked using BLAST analysis. The corresponding peptides were chemically synthesized in polymerazible forms using the t-Boc technique. Rabbits developed a high humoral response against these peptides as tested by a multiple antigen blot assay; it recognized native Sm31 in crude S. mansoni extracts and as circulating antigen in sera of S. mansoni-infected patients by western blot. Relevant antigenic determinants were located at the N- and C-terminus sequences. Antibodies against these regions recognized the native enzyme in an ELISA-like assay called cysteine protease immuno assay in which the immunocaptured enzyme was revealed by the intrinsic cathepsin B hydrolytic activity of Sm31. The method successfully and specifically detected Sm31 in sera of infected individuals, most of them (83.3%) with light infections, offering a rationale for the development of parasite enzyme capture assays using anti-synthetic peptide antibodies for possible use in the diagnosis of schistoso,iasis.

Roqueros y roqueras, pavitos y pavitas, skaters, lesbianas y gays: el papel del consumo cultural en la construcción de representaciones de identidades juveniles: el caso de algunos grupos de jóvenes que van a los malls en Maracaibo, Venezuela / Rockeros e rockeras, perus e peruas, skaters, lesbianas e gays: o papel do consumerismo cultural na construção social das representações das identidades dos jovens: o caso de grupos de jovens que freqüentam os malls da cidade de Maracaibo, Venezuela / Male and female rockers, Male and female turkeys, skaters, lesbians and gays: the role of cultural consumerism in the social construction of the representations of youth identities: the case of youth groups frequenting the local malls in Maracaibo, Venezuela

Este trabajo tiene como objetivo analizar cómo el consumo cultural se convierte en un elemento fundamental en el proceso de construcción de identidades y diferencias de algunos grupos de jóvenes en un contexto urbano y en espacios de intercambio de bienes materiales y simbólicos globalizados, como es el caso de los malls en Maracaibo. En función de este objetivo se tomaron, como categorías centrales de análisis, los conceptos de consumo cultural y representaciones de identidades. La metodología utilizada es de tipo cualitativo, privilegiando para la producción de la información el uso de técnicas etnográficas tales como la observación y las entrevistas en profundidad. Se concluye que en los procesos de construcción de representaciones de identidades de los jóvenes y las jóvenes en estudio, los objetos se tornan valiosos y adquieren centralidad en sus adscripciones identitarias, en la medida en que se convierten en el medio más importante para construir la imagen que desean comunicar para identificarse y diferenciarse de los otros jóvenes y de las otras jóvenes. Asimismo, que existen diferentes maneras de ser joven y que estas identidades se construyen en el entrecruzamiento de espacios y símbolos globales y locales.

Este trabalho tem como objetivo analisar como o consumo cultural se torna num elemento fundamental no processo de construção de identidades e diferenças de alguns grupos de jovens num contexto urbano e em espaços de troca de bens materiais e simbólicos globalizados, como é o caso dos malls da cidade de Maracaibo, Venezuela. Baseado neste objetivo, se tomaram como categorias centrais da análise, os conceitos de consumo cultural e representações de identidades. A metodologia utilizada é do tipo qualitativo, privilegiando o uso de técnicas etnográficas, tais como a observação e as entrevistas de profundidade, para a produção de informação. Se conclui que nos processos de construção de representações de identidades dos jovens e das jovens neste estudo, os objetos se tornam valiosos e adquirem centralidade nas suas adscrições identitárias, na medida em que se tornam no meio mais importante para construir a imagem que desejam comunicar para se identificar e para se diferenciar dos outros jovens e das outras jovens. Igualmente se conclui que há maneiras diferentes de ser jovem e que estas identidades se construem no cruzamento de espaços e símbolos globais e locais.

This paper has as its goal to analyze how cultural consumerism turns out to be a fundamental element in the process of construction of identites and differences in some youth groups in an urban context and in those spaces where globalized material and symbolic goods are interchanged, as it is the case of the malls of Maracaibo. To reach this goal, the concepts of cultural consumerism and identities representations were taken as central analytic categories. The methodology used in this study was qualitative, foregrounding ethnographic techiques for the collection of information, like observation and in-depth interviews. The conclusion is that in the proceses of identities representation construction in those youths under scrutiny, objects become valuable and acquire centrality in their identitary adscriptions in as much as they become the most important means to construct that image they wish to communicate in order to identfiy with, and differentiate themselves from other youths. It is also concluded that there are different ways of being young, and that those identites are constructed in the crossing of spaces and symbols that are both local and global.

Generic sodium stibogluconate is as safe and effective as branded meglumine antimoniate, for the treatment of tegumentary leishmaniasis in Isiboro Secure Park, Bolivia.

Human cutaneous leishmaniasis (CL) and mucous leishmaniasis (ML) are highly endemic in Isiboro Secure Park, which lies in the Bolivian department of Cochabamba--an area where branded meglumine antimoniate (Glucantime) is expensive and poorly distributed. The safety and efficacy of generic sodium stibogluconate (SSG), from Albert David Ltd, was therefore explored, in CL and ML cases from the park, who were treated with 20 mg/kg.day for 20 and 30 days, respectively. A questionnaire recording adverse effects was completed by a physician in each treatment centre. Efficacy of treatment was assessed at the end of treatment and at follow-ups 1 month and 3, 6 and 12 months later. Overall, 146 patients completed treatment with SSG in 2003-2004. No fatalities or severe adverse effects were reported but mild to moderate adverse effects were noted in 41 (28%) of the patients. The incidence of adverse effects was significantly higher among the cases of ML than among the cases of CL. Of the 86 patients with CL who completed 6 months of follow-up, 81 (94.2%) were considered to have been clinically cured; a comparable cohort of 69 CL cases who had been treated with Glucantime in 2001-2002 showed a similar frequency of clinical cure (90%). Generic SSG was shown to be safe and efficacious for the treatment of tegumentary leishmaniasis in Bolivia. Being several times cheaper than Glucantime, it could contribute to improving the access of CL and ML patients to treatment, not only in Bolivia but also in other countries of Latin America.

Schistosoma: cross-reactivity and antigenic community among different species.

It is not unusual to find common molecules among different species of the genus Schistosoma. When those molecules are antigenic, they may be used in immunodiagnosis and vaccines, but they could also be applied to taxonomic and evolutionary studies. To study cross-reactivity and antigenic community among different species of schistosomes, plasmas from laboratory animals infected with Schistosoma bovis, S. guineensis, S. rodhaini, S. haematobium, and four strains of S. mansoni were evaluated with a crude extract of adult worms of S. mansoni by Western blot. Using the multiple antigen blot assay, plasmas from these infected animals were exposed to a selected group of synthetic peptides from Sm28GST, Sm28TPI, Sm elastase, Sm97, Sm32, Sm31, and Sm Cathepsin L. The results presented herein demonstrate differential cross-reactivity and antigenic community among the Mansoni and Haematobium groups of schistosomes, which is of relevance as an additional new tool for phylogenetic studies of schistosomes as well as for diagnosis and vaccine purposes.

American tegumentary leishmaniasis: antigen-gene polymorphism, taxonomy and clinical pleomorphism.

Multi-locus enzyme electrophoresis is the current gold standard for the genetic characterisation of Leishmania. However, this method is time-consuming and, more importantly, cannot be directly applied to parasites present in host tissue. PCR-based methods represent an ideal alternative but, to date, a multi-locus analysis has not been applied to the same sample. This has now been achieved with a sample of 55 neotropical isolates (Leishmania (Viannia) braziliensis, L. (V.) peruviana, L. (V.) guyanensis, L. (V.) lainsoni and L. (L.) amazonensis), using five different genes as targets, four of which encoded major Leishmania antigens (gp63, Hsp70, H2B and Cpb). Our multi-locus approach strongly supports the current taxonomy and demonstrates a highly robust method of distinguishing different strains. Within L. (V.) braziliensis, we did not encounter so far specific genetic differences between parasites isolated from cutaneous and mucosal lesions. Interestingly, results provided by each of the different antigen-genes in the species considered, were different, suggesting different selective pressures. Our work emphasises the need for a multi-disciplinary approach to study the clinical pleomorphism of leishmaniasis.

Effect of bilayer thickness on membrane bending rigidity.

The bending rigidity k(c) of bilayer vesicles self-assembled from amphiphilic diblock copolymers has been measured using single- and dual-micropipet techniques. These copolymers are nearly a factor of 5 greater in hydrophobic membrane thickness d than their lipid counterparts and an order of magnitude larger in molecular weight M(n). The macromolecular structure of these amphiphiles lends insight into and extends relationships for traditional surfactant behavior. We find the scaling of k(c) with thickness to be nearly quadratic, in good agreement with existing theories for bilayer membranes. The results here are key to understanding and designing soft interfaces such as biomembrane mimetics.

Experiencia en prostatectomía radical laparoscópica / Experience in laparoscopic radical prostatectomy

La prostatectomía radical laparoscópica (PRL) es una nueva técnica quirúrgica que surge como alternativaa la prostatectomía radical abierta con el fin de reducir su morbilidad. Presentamos nuestra experienciainicial en PRL.Revisión retrospectiva de 17 pacientes operados entre marzo 2002 y agosto 2003 por PRL, por cáncer depróstata localizado, en 3 centros hospitalarios. Nueve pacientes fueron operados por vía transperitonealy 8 por vía extraperitoneal, sin conservación de bandeletas. Dos pacientes fueron sometidos alinfadenectomía íleo obturatriz. PSA preoperatorio promedio fue 9,5 ng/ml (rango 5,5-16,8).El tiempo operatorio promedio fue 5,1 h (rango 2,5-7), la mediana de sangrado estimado fue 500 cc(rango 100-2000 cc), con 2 transfusiones. Hubo 3 conversiones, una por tiempo prolongado de cirugía,otra por lesión de arteria epigástrica con hemorragia profusa y otra por imposibilidad de encontrar elcuello vesical. Hubo 3 complicaciones intraoperatorias resueltas por vía laparoscópica, lesión de arteriaepigástrica, perforación de vejiga, lesión de recto. La mediana de hospitalización fue 5 días (rango 4-19).La mediana de tiempo de catéter vesical fue de 6 días (rango 4 a 24). Hubo una fístula urinaria. Laetapificación patológica fue T2a (12 porciento), T2b (70 porciento), T3a (18 porciento), con 1 margen positivo en un pacienteT3a. La mediana de seguimiento fue de 3 meses (rango 1-15), con una sobrevida libre de tumor a 3 mesesde 95 porciento. Una continencia nocturna de 100 porciento y una continencia diurna de 85 porciento sin paños y de 15 porciento usando un paño.La prostatectomía radical laparoscópica es una técnica factible de realizar, que requiere una larga curvade aprendizaje para reducir los prolongados tiempos operatorios y la morbilidad perioperatoria. Se requierede un buen material laparoscópico y de un equipo quirúrgico afiatado y motivado (cirujanos,anestesista, arsenalera y personal de pabellón) para lograr resultados comparables a la técnica abierta.

Immunogenicity of polymerizable synthetic peptides derived from a vaccine candidate against schistosomiasis: the asparaginyl endopeptidase (Sm32).

The asparaginyl endopeptidase (Sm32) is expressed in the gastrodermal cells of the schistosome gut and in the head glands of the cercariae. Possibly, Sm32 hydrolyzes pro-proteins involved in the degradation of host hemoglobin [Parasitol. Today 12 (1996) 125]. Preliminary evidences using an Sj32/Sm32 murine vaccine have shown a profound effect on oviposition and worm burden [Chin. J. Schist. Control. 7 (1995) 72; Bull. Human Med. Univ. 24 (1999) 225; Vaccine 20 (2002) 439]. The importance of Sm32 as a novel vaccine candidate is based on the possibility of preventing the maturation of other cathepsins and/or preventing schistosome skin invasion. We studied the immunogenicity of polymerizable peptides derived from Sm32 to select potential protective epitopes. Sm32 prediction of T and B epitopes and homology studies with human legumain were performed. Among the variety of factors that influence the antibody response, we specifically examined the effect of: (i) genetic background of mouse strain, inbred (C57BL/6) versus outbred (Swiss) mice; and (ii) vaccination with a single peptide versus pool of peptides. Swiss mice raised antibodies to three different regions of the Sm32, as tested by the Multiple Antigen Blot Assay (MABA): 182-215 (peptides IMT-70 and 72), 244-273 (IMT-64) and 336-355 (IMT-66). None of these regions were immunogenic for C57BL/6. On the contrary, other peptides, IMT-4 (21-40), IMT-12 (101-120) and IMT-26 (292-313) were highly immunogenic for this inbred strain. Only Swiss mice immunized with a single peptide (IMT-64 and 72) or with three different pools of IMT-peptides (Pool A-II: 14, 16, 18, 70, 72, 89; pool A-III: 22, 64, 24, 26, 28 and pool A-V: 64, 66, 28, 70, 72) recognized the original protein in a crude extract of the worm antigen by Western blot. Peptides IMT-64, 14 and 26 were responsible for this recognition. In general, the vaccination with pool of peptides was more immunogenic for both mouse strains. Predicted B cell epitopes, with hydrophilicity scores over +10 (IMT-12, 64, 26) were always immunogenic after either single or combined peptide vaccination. Sm32 sequences 41-80 (IMT-6 and 8), 141-160 (IMT-16) and 182-215 (IMT-70 and 72) were nearly identical to the corresponding human legumain regions and should be excluded from the human vaccine. We can conclude that the regions of Sm32 that were recognized by antibodies of mice immunized with polymerizable peptides depended on the mice strain and on the hydrophilicity score of the peptides.

Plasmodium vivax CS peptides display conformational preferences for folded forms in solution.

Spectroscopic techniques have been used to study the conformations of several synthetic peptides with sequences corresponding to the repeat regions of the circumsporozoite proteins of Plasmodium vivax, variants vk-210 and vk-247. As has previously been shown for P. falciparum, turn-like folded conformations are observed, in rapid dynamic equilibrium with extended-chain forms. These results are consistent with the known similarity of the structural, biosynthetic and immunological properties of the circumsporozoite proteins of different plasmodial species. Additionally, the observation of folded conformers provides a rationale for the effectiveness of these peptides as immunogens and potential vaccines.

Laparoscopic partial nephrectomy for renal tumor: single center experience comparing clamping and no clamping techniques of the renal vasculature.

PURPOSE: We performed a nonrandomized retrospective comparison of 2 techniques for laparoscopic partial nephrectomy, that is without and with clamping the renal vessels. MATERIALS AND METHODS: Between December 1997 and February 2002, 28 consecutive patients underwent transperitoneal laparoscopic partial nephrectomy for renal tumor. In group 1 (12 patients) partial nephrectomy was performed with ultrasonic shears and bipolar cautery without clamping the renal vessels, while in group 2 (16 patients) the renal pedicle was clamped before tumor excision. In group 2 patients intracorporeal kidney cooling was achieved by a ureteral catheter connected to 4C solution. Intracorporeal freehand suturing techniques were used to close the collecting system when opened and approximate the renal parenchyma. RESULTS: All procedures were successfully completed laparoscopically. Mean renal ischemia time +/- SD was 27.3 +/- 7 minutes (range 15 to 47) in group 2 patients. Mean laparoscopic operating time was 179.1 +/- 86 minutes (range 90 to 390) in group 1 compared with 121.5 +/- 37 minutes (range 60 to 210) in group 2 (p = 0.004). Mean intraoperative blood loss was significantly higher in group 1 than in group 2 (708.3 +/- 569 versus 270.3 +/- 281 ml., p = 0.014). Three patients in group 1 and 2 in group 2 required blood transfusions. Immediately postoperatively mean creatinine was 1.26 +/- 0.36 and 1.45 +/- 0.61 mg./dl. in groups 1 and 2, respectively (p = 0.075). Surgical margins were negative in all specimens. Pathological examination revealed renal cell cancer in 18 cases (stages pT1 in 17 and pT3a in 1), oncocytoma in 4, angiomyolipoma in 5 and renal adenoma in 1. CONCLUSIONS: Laparoscopic partial nephrectomy represents a feasible option for patients with small renal masses. Clamping the renal vessels during tumor resection and suturing the kidney mimics the open technique and seems to be associated with less blood loss and shorter laparoscopic operative time.

Laboratory diagnosis of Schistosomiasis in areas of low transmission: a review of a line of research.

After 57 years of successful control of schistosomiasis in Venezuela, the prevalence and intensity of infection have declined. Approximately 80% of the individuals eliminate less than 100 eggs/g of stools, therefore morbidity is mild and the majority are asymptomatic. The sensitivity of Kato-Katz decreases to approximately 60%. Available serological methods for the detection of circulating antigens only reach a 70% of sensitivity. Tests based on the detection of antibodies by immunoenzymatic assays have been improved. The circumoval precipitine test has shown a high sensitivity (97%), specificity (100%), and correlation with oviposition, being considered the best confirmatory diagnostic test. Additionally to the classical immunoenzymatic assays, the development of the alkaline phosphatase immunoassay, allowed to reach a 100% specificity with an 89% sensitivity. Recently, we have developed a modified ELISA in which the soluble egg antigen is treated with sodium metaperiodate (SMP-ELISA) in order to eliminate the glycosilated epitopes responsible for the false positive reactions. The specificity and sensitivity reaches 97% and 99%, respectively. Synthetic peptides from the excretory-secretory enzymes, cathepsin B (Sm31) legumain (Sm32) and cathepsin D (Sm45), have been synthesized. The combination of two peptides derived from the Sm31 have been evaluated, reaching a sensitivity of 96% when analyzed independently and with a 100% specificity. Antibodies raised in rabbits against peptides derived from the Sm31 and Sm32 are currently evaluated in two different antigen-capture-based assays. The development of a simple, cheap and reliable test that correlates with parasite activity is a major goal.

Laboratory diagnosis of Schistosomiasis in areas of low transmission. A review of a line of research

After 57 years of successful control of schistosomiasis in Venezuela, the prevalence and intensity of infection have declined. Approximately 80 percent of the individuals eliminate less than 100 eggs/g of stools, therefore morbidity is mild and the majority are asymptomatic. The sensitivity of Kato-Katz decreases to approximately 60 percent. Available serological methods for the detection of circulating antigens only reach a 70 percent of sensitivity. Tests based on the detection of antibodies by immunoenzymatic assays have been improved. The circumoval precipitine test has shown a high sensitivity (97 percent), specificity (100 percent), and correlation with oviposition, being considered the best confirmatory diagnostic test. Additionally to the classical immunoenzymatic assays, the development of the alkaline phosphatase immunoassay, allowed to reach a 100 percent specificity with an 89 percent sensitivity. Recently, we have developed a modified ELISA in which the soluble egg antigen is treated with sodium metaperiodate (SMP-ELISA) in order to eliminate the glycosilated epitopes responsible for the false positive reactions. The specificity and sensitivity reaches 97 percent and 99 percent, respectively. Synthetic peptides from the excretory-secretory enzymes, cathepsin B (Sm31) legumain (Sm32) and cathepsin D (Sm45), have been synthesized. The combination of two peptides derived from the Sm31 have been evaluated, reaching a sensitivity of 96 percent when analyzed independently and with a 100 percent specificity. Antibodies raised in rabbits against peptides derived from the Sm31 and Sm32 are currently evaluated in two different antigen-capture-based assays. The development of a simple, cheap and reliable test that correlates with parasite activity is a major goal

Immunogenicity of synthetic peptides from the Sm31 antigen (cathepsin B) of the Schistosoma mansoni adult worms.

The chemical synthesis of peptides may simplify the production of molecules for diagnosis of Schistosoma mansoni. Seventeen polymeric, 20-amino acids long, peptides comprising the entire Sm31 molecule of the adult worm, were synthesized under the t-boc strategy and their immunogenicity was evaluated. Of these, 10 peptides were immunogenic in rabbits. The peptides containing the sequence Gly74-Ser93 (peptide IMT-172) and the sequence Val154-Ala173 (peptide IMT-180) were responsible for the recognition of the Sm31 molecule by Western blot. This was confirmed by the specific inhibition of recognition of each molecule with the homologous peptide. Additionally, antibodies against these peptides strongly fixed to the adult worm gut. The present results, together with the strong immunogenicity shown for the adult worm 31 kDa antigen, establish the basis for the development of an immunodiagnostic method using synthetic peptides.

Electromechanical limits of polymersomes.

Self-assembled membranes of amphiphilic diblock copolymers enable comparisons of cohesiveness with lipid membranes over the range of hydrophobic thicknesses d = 3-15 nm. At zero mechanical tension the breakdown potential V(c) for polymersomes with d = 15 nm is 9 V, compared to 1 V for liposomes with d = 3 nm. Nonetheless, electromechanical stresses at breakdown universally exhibit a V(c)(2) dependence, and membrane capacitance shows the expected strong d dependence, conforming to simple thermodynamic models. The viscous nature of the diblock membranes is apparent in the protracted postporation dynamics.

Preparation, stability, and in vitro performance of vesicles made with diblock copolymers.

Vesicles made completely from diblock copolymers-polymersomes-can be stably prepared by a wide range of techniques common to liposomes. Processes such as film rehydration, sonication, and extrusion can generate many-micron giants as well as monodisperse, approximately 100 nm vesicles of PEO-PEE (polyethyleneoxide-polyethylethylene) or PEO-PBD (polyethyleneoxide-polybutadiene). These thick-walled vesicles of polymer can encapsulate macromolecules just as liposomes can but, unlike many pure liposome systems, these polymersomes exhibit no in-surface thermal transitions and a subpopulation even survive autoclaving. Suspension in blood plasma has no immediate ill-effect on vesicle stability, and neither adhesion nor stimulation of phagocytes are apparent when giant polymersomes are held in direct, protracted contact. Proliferating cells, in addition, are unaffected when cultured for an extended time with an excess of polymersomes. The effects are consistent with the steric stabilization that PEG-lipid can impart to liposomes, but the present single-component polymersomes are far more stable mechanically and are not limited by PEG-driven micellization. The results potentiate a broad new class of technologically useful, polymer-based vesicles.