Long duration stabilization of porous silicon membranes in physiological media: Application for implantable reactors.

The natural biodegradabilty of porous silicon (pSi) in physiological media limits its wider usage for implantable systems. We report the stabilization of porous silicon (pSi) membranes by chemical surface oxidation using RCA1 and RCA2 protocols, which was followed by a PEGylation process using a silane-PEG. These surface modifications stabilized the pSi to allow a long period of immersion in PBS, while leaving the pSi surface sufficiently hydrophilic for good filtration and diffusion of several biomolecules of different sizes without any blockage of the pSi structure. The pore sizes of the pSi membranes were between 5 and 20 nm, with the membrane thickness around 70 µm. The diffusion coefficient for fluorescein through the membrane was 2 × 10-10 cm2 s-1, and for glucose was 2.2 × 10-9 cm2 s-1. The pSi membrane maintained that level of glucose diffusion for one month of immersion in PBS. After 2 months immersion in PBS the pSi membrane continued to operate, but with a reduced glucose diffusion coefficient. The chemical stabilization of pSi membranes provided almost 1 week stable and functional biomolecule transport in blood plasma and opens the possibility for its short-term implantation as a diffusion membrane in biocompatible systems.

Impact of Surface Chemistry on Copper Deposition in Mesoporous Silicon.

An easy, efficient, and safe process is developed to metallize mesoporous silicon (PSi) with Cu from the decomposition of a solution of mesitylcopper (CuMes) in an imidazolium-based ionic liquid (IL), [C1C4Im][NTf2]. The impregnation of a solution of CuMes in IL affords the deposition of metallic islands not only on the surface but also deep within the pores of a mesoporous Si layer with small pores below 10 nm. Therefore, this process is well suited to efficiently and completely metallize PSi layers. An in-depth mechanistic study shows that metal deposition is due to the reduction of CuMes by surface silane groups rather than by Si oxidation as observed in aqueous or water-containing media. This could open a new route to the chemical metallization of PSi by less-noble metals difficult to attain by a conventional displacement reaction.

An Efficient, Versatile, and Safe Access to Supported Metallic Nanoparticles on Porous Silicon with Ionic Liquids.

The metallization of porous silicon (PSi) is generally realized through physical vapor deposition (PVD) or electrochemical processes using aqueous solutions. The former uses a strong vacuum and does not allow for a conformal deposition into the pores. In the latter, the water used as solvent causes oxidation of the silicon during the reduction of the salt precursors. Moreover, as PSi is hydrophobic, the metal penetration into the pores is restricted to the near-surface region. Using a solution of organometallic (OM) precursors in ionic liquid (IL), we have developed an easy and efficient way to fully metallize the pores throughout the several-µm-thick porous Si. This process affords supported metallic nanoparticles characterized by a narrow size distribution. This process is demonstrated for different metals (Pt, Pd, Cu, and Ru) and can probably be extended to other metals. Moreover, as no reducing agent is necessary (the decomposition in an argon atmosphere at 50 °C is fostered by surface silicon hydride groups borne by PSi), the safety and the cost of the process are improved.

Loss of AP-2delta reduces retinal ganglion cell numbers and axonal projections to the superior colliculus.

BACKGROUND: AP-2δ is the most divergent member of the Activating Protein-2 (TFAP2) family of transcription factors. AP-2δ is restricted to specific regions of the CNS, including a subset of ganglion cells in the retina. Retinal ganglion cells (RGCs), the only output neurons of the retina, are responsible for transmitting the visual signal to the brain. RESULTS: AP-2δ knockout results in loss of Brn3c (Pou4f3) expression in AP-2δ -positive RGCs. While AP-2δ-/- mice have morphologically normal retinas at birth, there is a significant reduction in retinal ganglion cell numbers by P21, after eye opening. Chromatin immunoprecipitation indicates that Brn3c is a target of AP-2δ in the retina. Using fluorochrome-conjugated cholera toxin subunit B to trace ganglion cell axons from the eye to the major visual pathways in the brain, we found 87 % and 32 % decreases in ipsilateral and contralateral projections, respectively, to the superior colliculus in AP-2δ-/- mice. In agreement with anatomical data, visually evoked responses recorded from the brain confirmed that retinal outputs to the brain are compromised. CONCLUSIONS: AP-2δ is important for the maintenance of ganglion cell numbers in the retina. Loss of AP-2δ alters retinal axonal projections to visual centers of the brain, with ipsilaterial projections to the superior colliculus being the most dramatically affected. Our results have important implications for integration of the visual signal at the superior colliculus.

Retinal distribution of Disabled-1 in a diurnal murine rodent, the Nile grass rat Arvicanthis niloticus.

We sought to study the expression pattern of Disabled-1 (Dab1; an adaptor protein in the reelin pathway) in the cone-rich retina of a diurnal murine rodent. Expression was examined by western blotting and immunohistochemistry using well-established antibodies against Dab1 and various markers of retinal neurons. Western blots revealed the presence of Dab1 (80 kDa) in brain and retina of the Nile grass rat. Retinal immunoreactivity was predominant in soma and dendrites of horizontal cells as well as in amacrine cell bodies aligned at the INL/IPL border. Dab1(+) neurons in the inner retina do not stain for parvalbumin, calbindin, protein kinase C-alpha, choline acetyltransferase, glutamic acid decarboxylase, or tyrosine hydroxylase. They express, however, the glycine transporter GlyT1. They have small ovoid cell bodies (7.1 ± 1.06 µm in diameter) and bistratified terminal plexii in laminas a and b of the IPL. Dab1(+) amacrine cells are evenly distributed across the retina (2600 cells/mm(2)) in a fairly regular mosaic (regularity indexes ≈3.3-5.5). We conclude that retinal Dab1 in the adult Nile grass rat exhibits a dual cell patterning similar to that found in human. It is expressed in horizontal cells as well as in a subpopulation of glycinergic amacrine cells undetectable with antibodies against calcium-binding proteins. These amacrine cells are likely of the AII type.

Long-term retinal cone survival and delayed alteration of the cone mosaic in a transgenic mouse model of stargardt-like dystrophy (STGD3).

PURPOSE: To examine the pattern of cone degeneration in the retina of a transgenic mouse model of Stargartd-like dystrophy (STGD3). METHODS: Investigations were performed on ELOVL4/TG1-2 transgenic (TG) mice and wild-type (WT) littermates from 1 to 24 months of age. Phenotypes were assessed by fundus imaging, fatty acid analysis, and electroretinogram (ERG) recording. Cone degeneration pattern was determined on retina whole mounts using immunohistochemistry and Voronoi domain analyses. RESULTS: Consistent with low transgene expression, photoreceptors degenerate very slowly. At 1 month, anatomical structure and fatty acid composition of the TG retina is comparable with WT. Rod loss appears at 2 months, exhibiting a central to peripheral gradient, and fundus defects are observed at 3 months. In contrast, cone morphology, distribution and function are still normal at 12 months. Cone loss becomes apparent at 15 months when the outer nuclear layer is reduced to 3 to 4 photoreceptor rows. This process starts at the center of the retina and affects cone subtypes similarly. Very few cones remain at 24 months, after all rods have disappeared (18 months). Quantitative studies focusing on cones expressing M-opsin show a net increase in Voronoi domains and a significant decrease in regularity indexes only beyond 15 months. CONCLUSIONS: Photoreceptor degeneration in this STGD3 mouse model follows the time course of a slow rod-cone dystrophy. The cone mosaic is preserved for almost 1 year after the onset of rod loss. This long delay provides an opportunity to examine rod-cone interactions during retinal degeneration and to test therapeutic effectiveness at protracting cone dysfunction.

Retinorecipient areas in the diurnal murine rodent Arvicanthis niloticus: A disproportionally large superior colliculus.

The Nile grass rat (Arvicanthis niloticus) has a high proportion of cone photoreceptors (∼30-40%) compared with that in the common laboratory mouse and rat (∼1-3%) and may prove a preferable murine model with which to study cone-driven information processing in retina and primary visual centers. However, other than regions involved in circadian control, little is known about the retinorecipient structures in this rodent. We undertook a detailed analysis of the retinal projections as revealed after intravitreal injection of the anterograde tracer cholera toxin subunit B. Retinal efferents were evaluated in 45 subcortical structures. Contralateral projections were always dominant. Major contralateral inputs consisted of the suprachiasmatic nucleus, dorsolateral geniculate nucleus (dLGN), intergeniculate leaflet, ventral geniculate nucleus (magnocellular part), lateroposterior thalamic nucleus, all six pretectal nuclei, superficial layers of the superior colliculus (SC), and the main nuclei of the accessory optic system. Terminals from the contralateral eye were also localized in an unnamed field rostromedial to the dLGN as well as in the subgeniculate thalamic nucleus. Ipsilateral inputs were found mainly in the suprachiasmatic nucleus, dLGN, intergeniculate leaflet, internal sector of the magnocellular part of the ventral geniculate nucleus, olivary pretectal nucleus, and SC optic layer. Retinal afferents were not detected in the basal forebrain or the dorsal raphe nucleus. Morphometric measurements revealed that the superficial layers of the SC are disproportionately enlarged relative to other retinorecipient regions and brain size compared with rats and mice. We suggest that this reflects the selective projection of cone-driven retinal ganglion cells to the SC. J. Comp. Neurol. 521:1699-1726, 2013. © 2012 Wiley Periodicals, Inc.

Retinorecipient areas in the diurnal murine rodent Arvicanthis niloticus: a disproportionally large superior colliculus.

The Nile grass rat (Arvicanthis niloticus) has a high proportion of cone photoreceptors (∼30-40%) compared with that in the common laboratory mouse and rat (∼1-3%) and may prove a preferable murine model with which to study cone-driven information processing in retina and primary visual centers. However, other than regions involved in circadian control, little is known about the retinorecipient structures in this rodent. We undertook a detailed analysis of the retinal projections as revealed after intravitreal injection of the anterograde tracer cholera toxin subunit B. Retinal efferents were evaluated in 45 subcortical structures. Contralateral projections were always dominant. Major contralateral inputs consisted of the suprachiasmatic nucleus, dorsolateral geniculate nucleus (dLGN), intergeniculate leaflet, ventral geniculate nucleus (magnocellular part), lateroposterior thalamic nucleus, all six pretectal nuclei, superficial layers of the superior colliculus (SC), and the main nuclei of the accessory optic system. Terminals from the contralateral eye were also localized in an unnamed field rostromedial to the dLGN as well as in the subgeniculate thalamic nucleus. Ipsilateral inputs were found mainly in the suprachiasmatic nucleus, dLGN, intergeniculate leaflet, internal sector of the magnocellular part of the ventral geniculate nucleus, olivary pretectal nucleus, and SC optic layer. Retinal afferents were not detected in the basal forebrain or the dorsal raphe nucleus. Morphometric measurements revealed that the superficial layers of the SC are disproportionately enlarged relative to other retinorecipient regions and brain size compared with rats and mice. We suggest that this reflects the selective projection of cone-driven retinal ganglion cells to the SC.

Dietary docosahexaenoic acid supplementation prevents age-related functional losses and A2E accumulation in the retina.

PURPOSE: With age, retina function progressively declines and A2E, a constituent of the toxin lipofuscin, accumulates in retinal pigment epithelial (RPE) cells. Both events are typically exacerbated in age-related retina diseases. We studied the effect of dietary docosahexaenoic acid (DHA, C22:6n-3) supplementation on these events, using a transgenic mouse model (mutant human ELOVL4; E4) displaying extensive age-related retina dysfunction and massive A2E accumulation. METHODS: Retina function was assessed with the electroretinogram (ERG) and A2E levels were measured in E4 and wildtype (WT) mice. Dietary DHA was manipulated from 1 to 3, 1 to 6, 6 to 12, and 12 to 18 months: 1% DHA over total fatty acids (E4+, WT+) or similar diet without DHA (E4-, WT-). RESULTS: Increased omega-3/6 ratios (DHA/arachidonic acid) in E4+ and WT+ retinas were confirmed for the 1- to 3-month and 1- to 6-month trials. Although 1- to 3-month intervention had no effects, when prolonged to 1 to 6 months, RPE function (ERG c-wave) was preserved in E4+ and WT+. Intervention from 6 to 12 months led to maintained outer and inner retina function (ERG a- and b-wave, respectively) in E4+. At 12 to 18 months, a similar beneficial effect on retina function occurred in WT+; A2E levels were reduced in E4+ and WT+. CONCLUSIONS: DHA supplementation was associated with: preserved retina function at mid-degenerative stages in E4 mice; prevention of age-related functional losses in WT mice; and reduced A2E levels in E4 and WT mice at the oldest age examined. These findings imply that dietary DHA could have broad preventative therapeutic applications (acting on pathologic and normal age-related ocular processes).

Case-based lung image categorization and retrieval for interstitial lung diseases: clinical workflows.

PURPOSE: Clinical workflows and user interfaces of image-based computer-aided diagnosis (CAD) for interstitial lung diseases in high-resolution computed tomography are introduced and discussed. METHODS: Three use cases are implemented to assist students, radiologists, and physicians in the diagnosis workup of interstitial lung diseases. RESULTS: In a first step, the proposed system shows a three-dimensional map of categorized lung tissue patterns with quantification of the diseases based on texture analysis of the lung parenchyma. Then, based on the proportions of abnormal and normal lung tissue as well as clinical data of the patients, retrieval of similar cases is enabled using a multimodal distance aggregating content-based image retrieval (CBIR) and text-based information search. The global system leads to a hybrid detection-CBIR-based CAD, where detection-based and CBIR-based CAD show to be complementary both on the user's side and on the algorithmic side. CONCLUSIONS: The proposed approach is in accordance with the classical workflow of clinicians searching for similar cases in textbooks and personal collections. The developed system enables objective and customizable inter-case similarity assessment, and the performance measures obtained with a leave-one-patient-out cross-validation (LOPO CV) are representative of a clinical usage of the system.

Differential gene expression in eyecup and retina of a mouse model of Stargardt-like macular dystrophy (STGD3).

PURPOSE: To investigate differentially expressed genes in eyecup and retina of the ELOVL4 transgenic mouse, a model of Stargardt-like macular dystrophy (STGD3). METHODS: We examined gene and protein expression in known pathways relevant to retinal degeneration using PCR arrays, Western blotting, and immunohistochemistry. Investigations were performed on ELOVL4 transgenic mice at 9 months, when 50% of rod (but no cone) photoreceptors had degenerated. Age-matched wild-type littermates served as controls. RESULTS: Significant expression level changes were found in only 17 of the 252 genes examined. Nine were upregulated (Fgf2, Fgfr1, Ntf5, Cbln1, Ngfr, Ntrk1, Trp53, Tlr6, and Herpud1), and eight were downregulated (Ccl22, Ccr3, Il18rap, Nf1, Ccl11, Atf6ß, Rpn1, and Serp1). Overexpression of FGF2 was detected at 1 month, before rod loss onset, and was maintained at high levels until cone loss (18 months). By 9 months, FGF2 overexpression was seen in photoreceptor cell bodies. Increased glial fibrillary acidic protein (GFAP) expression due to glial cell reactivity followed the same time course. Levels of NGFR/p75NTR remained invariant. Although present in rod outer segments at 1 month, the macrophage chemoattracting chemokine CCL22 became undetectable by 9 months, a likely consequence of progressive rod outer segment truncation. CONCLUSIONS: At a mid-degeneration stage, major changes in gene expression in the ELOVL4 transgenic mouse retina included upregulation of Fgf2 and Fgfr1 and downregulation of Ccl22. Modulation of FGF2 occurred very early, concomitant with an increase in GFAP expression. Future studies will address which factors upstream of Fgf2 could provide potential therapeutic targets to slow photoreceptor degeneration in STGD3.

Differential changes in retina function with normal aging in humans.

We evaluated the full field electroretinogram (ERG) to assess age-related changes in retina function in humans. ERG recordings were performed on healthy subjects with normal fundus appearance, lack of cataract and 20/20 acuity, aged 20-39 years (n = 27; mean age 25 ± 5, standard deviation), 40-59 years (n = 20; mean 53 ± 5), and 60-82 years (n = 18; mean 69 ± 5). Multiple ERG tests were applied, including light and dark-adapted stimulus-response function, dark adaptation and dynamic of recovery from a single bright flash under dark-adapted conditions. Changes in ERG properties were found in the oldest age group when compared with the two younger age groups. (1) The photopic hill effect was less pronounced. (2) Both photopic a-wave and b-wave amplitudes and implicit times were increased at high stimulus strengths. (3) Dark adaptation time was delayed for pure rod and L/M cone-driven responses, respectively. (4) Dark-adapted a-wave but not b-wave amplitudes were reduced, yielding higher B/A ratios. (5) Dark-adapted a- and b-waves implicit times were prolonged: there was a direct proportional correlation between minimal a-wave implicit times and age. (6) The dynamic of dark current recovery from a bright flash, under dark-adapted conditions, was transiently faster at intervals between 0.9 and 2 s. These results denote that aging of the healthy retina is accompanied by specific functional changes, which must be taken into account to optimally diagnose potential pathologies.

Inner retina remodeling in a mouse model of stargardt-like macular dystrophy (STGD3).

Purpose. To investigate the impact of progressive age-related photoreceptor degeneration on retinal integrity in Stargardt-like macular dystrophy (STGD3). Methods. The structural design of the inner retina of the ELOVL4 transgenic mouse model of STGD3 was compared with that of age-matched littermate wild-type (WT) mice from 1 to 24 months of age by using immunohistofluorescence and confocal microscopy and by relying on antibodies against cell-type-specific markers, synapse-associated proteins, and neurotransmitters. Results. Müller cell reactivity occurred at the earliest age studied, before photoreceptor loss. This finding is perhaps not surprising, considering the cell's ubiquitous roles in retina homeostasis. Second-order neurons displayed salient morphologic changes as a function of photoreceptoral input loss. Age-related sprouting of dendritic fibers from rod bipolar and horizontal cells into the ONL did not occur. In contrast, with the loss of photoreceptor sensory input, these second-order neurons progressively bore fewer synapses. After rod loss, the few remaining cones showed abnormal opsin expression, revealing tortuous branched axons. After complete ONL loss (beyond 18 months of age), localized areas of extreme retinal disruptions were observed in the central retina. RPE cell invasion, dense networks of strongly reactive Müller cell processes, and invagination of axons and blood vessels were distinctive features of these regions. In addition, otherwise unaffected cholinergic amacrine cells displayed severe perturbation of their cell bodies and synaptic plexi in these areas. Conclusions. Remodeling in ELOVL4 transgenic mice follows a pattern similar to that reported after other types of hereditary retinopathies in animals and humans, pointing to a potentially common pathophysiologic mechanism.

Topographic arrangement of S-cone photoreceptors in the retina of the diurnal Nile grass rat (Arvicanthis niloticus).

PURPOSE: The retina of Arvicanthis niloticus, a diurnal murine rodent closely related to Rattus (rats) and Mus (mice), contains approximately 30% to 35% cones and has several cone-driven functional characteristics found in humans. In this study the organization of these cone photoreceptors was examined, with emphasis on those expressing the S-opsin photopigment (S-cones). METHODS: Cones were labeled with antibodies against M- and S-opsins. Their topographic arrangement was examined on images of retinal flatmounts using density measures, nearest-neighbor distance, and Voronoi domain analysis. Partial sequencing of the S-opsin DNA was also performed to determine whether this visual pigment was blue/violet or UV sensitive. RESULTS: Cone photoreceptors (estimated total population approximately 1.450 million) came in two distinct types that express either M/L- or S-opsin. Both types were present across the retinal surface. S-cones (approximately 7-8% of the total cone population) achieved a higher density in a discrete temporodorsal sector of the retina. The S-cone mosaic was irregular. Finally, S-cones were likely to be UV sensitive, according to genetic analysis. CONCLUSIONS: The topographic arrangement of cone photoreceptors in the retina of the diurnal Nile grass rat A. niloticus represents a highly pertinent model to improve understanding of the pathologic course of and related therapy for retinal disease involving cones.

Fetal tissue allografts in the damaged adult visual cortex: physiology and connectivity.

During the past three decades, many studies have examined the capacity of embryonic neural grafts (dissociated cells or tissue blocks) to restore lost functions following various damages to the adult mammalian brain. Only very few focused on the visual system even if it is the optimal system to examine the potential of embryonic neural grafts in repairing point-to-point networks. Collectively, these studies show that, within limits, homologous sheets of fetal tissue grafted in the occipital cortex of adult rodents integrate into the host visual circuitry and are physiologically active.

The electroretinogram (ERG) of a diurnal cone-rich laboratory rodent, the Nile grass rat (Arvicanthis niloticus).

The most widespread models to study blindness, rats and mice, have retinas containing less than 3% cones. The diurnal rodent Arvicanthis niloticus retina has around 35% cones. Using ERG recordings, we studied retina function in this species. Several features differed from that reported in rats and mice: (a) fivefold larger photopic a-wave amplitudes; (b) photopic hill effect in Nile grass rats only; and (c) flicker amplitude plateau between 5 to 35 Hz with fusion beyond 60 Hz in Nile grass rats only. We conclude that A. niloticus might complement rats and mice for studying retinal function and pathologies involving cones.

Retinal anatomy and visual performance in a diurnal cone-rich laboratory rodent, the Nile grass rat (Arvicanthis niloticus).

Unlike laboratory rats and mice, muridae of the Arvicanthis family (A. ansorgei and A. niloticus) are adapted to functioning best in daylight. To date, they have been used as experimental models mainly in studies of circadian rhythms. However, recent work aimed at optimizing photoreceptor-directed gene delivery vectors (Khani et al. [2007] Invest Ophthalmol Vis Sci 48:3954-3961) suggests their potential usefulness for studying retinal pathologies and therapies. In the present study we analyzed the retinal anatomy and visual performance of the Nile grass rat (A. niloticus) using immunohistofluorescence and the optokinetic response (OKR). We found that approximately 35-40% of photoreceptors are cones; that many neural features of the inner retina are similar to those in other diurnal mammals; and that spatial acuity, measured by the OKR, is more than two times that of the usual laboratory rodents. These observations are consistent with the known diurnal habits of this animal, and further support its pertinence as a complementary model for studies of structure, function, and pathology in cone-rich mammalian retinae.

Cell-based therapy for retina degeneration: the promise of a cure.

Cell-based therapies in the retina have been associated with the recovery of visual function in animal models of retinal degeneration. This review covers the current status of such therapies with regard to the source of the donor cells, their integration, and their impact on the degenerating host retina. Emphasis is also put on the importance of a careful interpretation of what is meant by "recovery of visual function". Two main approaches are considered here: (1) the use of human embryonic stem cell derived retinal pigment epithelial (RPE) cells to rescue photoreceptors in an animal model of RPE defect; and (2) the use of photoreceptor precursors to repair the degenerating neural retina. The current conclusions are that major hurdles have to be dealt with, such as finding an appropriate and ethically compliant donor cell source that would yield protracted survival and integration of the replacement retinal cells, and that there is no evidence yet that cell-based therapies can allow the long-term preservation or recovery of conscious vision.

Heterotopic, not homotopic, fetal occipital allografts in adult hosts project to visual-related extracortical targets.

PURPOSE: Fetal occipital allografts implanted into the posterior cortex of adult mice project massively throughout the ipsilateral pallium of the host, but rarely outside this domain (Gaillard et al., 2004). The present study was undertaken to examine in detail whether this pattern is specific to graft location. METHODS: Cortical fragments corresponding to presumptive occipital areas were harvested from E15 mice fetuses expressing ubiquitously the eGFP protein, and implanted in correct (homotopic) and incorrect (heterotopic) cortical loci in wild-type adults. Two months later, efferents were detected by immunohistochemistry and quantified on selected DAB-treated sections. RESULTS: The present findings show (i) that robust projections are present in the ipsilateral host cortex regardless of the graft location; (ii) that 55% the grafts located in parietal and frontal cortices have obvious but sparse callosal and subcortical projections; and (iii) that grafts placed in occipital areas never contact ipsilateral subcortical targets, likely because graft-related axons are unable to cross obliquely the thalamocortical fascicles in the underlying white matter. CONCLUSIONS: These puzzling results question the use of transplantation strategies for repairing damaged networks in adults where rewiring involves complex white matter trajectories.

Glucose-targeted niosomes deliver vasoactive intestinal peptide (VIP) to the brain.

The aim of this study was to evaluate glucose-bearing niosomes as a brain targeted delivery system for the vasoactive intestinal peptide (VIP). To this end, VIP/125I-VIP-loaded glucose-bearing niosomes were intravenously injected to mice. Brain uptake was determined by measuring the radioactivity of 125I-labeled VIP using gamma-counting, after intravenous administration of VIP in solution or encapsulated in glucose-bearing niosomes or in control niosomes. VIP integrity was assessed by reversed-phase HPLC analysis of brain extracts. Distribution of 125I-VIP derived radioactivity was examined from serial brain slices. HPLC analysis confirmed the presence of intact VIP in brain after administration of VIP-loaded niosomes, but not after administration of VIP solution. Encapsulation within glucose-bearing niosomes mainly allowed a significantly higher VIP brain uptake compared to control niosomes (up to 86%, 5min after treatment). Brain distribution of intact VIP after injection of glucose-bearing niosomes, indicated that radioactivity was preferentially located in the posterior and the anterior parts of the brain, whereas it was homogeneously distributed in the whole brain after the administration of control vesicles. In conclusion, this novel vesicular formulation of VIP delivers intact VIP to particular brain regions in mice. Glucose-bearing vesicles might be therefore a novel tool to deliver drugs across the blood-brain barrier (BBB).