The active transport of polypeptides in the rabbit nasal mucosa is supported by a specific vesicular transport inhibited by cytochalasin D

Cremaschi, D.; Porta, Cristina; Ghirardelli, Roberta

doi:10.1016/0005-2736(96)00081-8

Cited by 15 publications

(6 citation statements)

References 10 publications

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“…So far, the mechanisms involved in the transport of hCT through nasal mucosa were largely unkown. Previously, a receptor-mediated uptake was postulated for [1,7Asu]eel calcitonin (8) but has not yet been confirmed (28,31). In this work, we suggest that internalization of hCT into the mucosa is associated with β-sheet-induced self-assembly of the C-terminal segment of the peptide.…”

Section: Discussionmentioning

confidence: 56%

Translocation of Human Calcitonin in Respiratory Nasal Epithelium Is Associated with Self-Assembly in Lipid Membrane

et al. 1998

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We studied the mechanisms involved in the translocation of human calcitonin (hCT) through excised bovine nasal mucosa (net mucosal-to-serosal permeability approximately 10(-)5 cm s-1). To determine structural requirements for the suggested vesicular internalization two carboxyfluorescein-labeled (fl) hCT fragments, the C-terminal fragment [Nalpha-fl]hCT(9-32) and the N-terminal fragment [Lys(fl)18]hCT(1-24) were synthesized. In presence of the endocytosis inhibitor cytochalasin D mucosal-to-serosal and serosal-to-mucosal hCT permeabilities were equal. Pathway visualization by confocal laser scanning microscopy showed punctated fluorescence indicating vesicular internalization of both hCT and [Nalpha-fl]hCT(9-32). In contrast, the N-terminal fragment lacking the beta-sheet forming C-terminus (25-32) was not internalized. Circular dichroism showed that, when interacting with neutral and negatively charged liposomes, hCT adopts beta-sheet conformation. In a concentrated aqueous solution, beta-sheet formation induces hCT self-assembly and fibrillation. High partitioning of hCT into lipid bilayer membranes was reflected by an apparent partition coefficient log D(pH 7.4) = 2.5 (liposome-buffer equilibrium dialysis). We propose that the high lipid partitioning and beta-sheet formation result in C-terminus-restricted supramolecular self-assembly of hCT and [Nalpha-fl]hCT(9-32) in lipid membranes. Vesicular internalization is suggested to be associated with self-assembly induced perturbation of the lipid bilayer. Condensed hCT self-assemblies may explain the high capacity of net mucosal-to-serosal hCT permeation, which compares favorably with the low transport capacity of receptor-mediated endocytosis.

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Section: Discussionmentioning

confidence: 56%

Translocation of Human Calcitonin in Respiratory Nasal Epithelium Is Associated with Self-Assembly in Lipid Membrane

et al. 1998

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“…Thus the majority of free polypeptide molecules moves through the larger area of the first two populations of pores and a negligible minority moves through the third population. The third class of pores probably is not located in intercellular junctions but in a very few nanolesions of the epithelium, such as damaged cells (3,6).…”

Section: Discussionmentioning

confidence: 99%

“…The polypeptides were adsorbed on nanoparticles by using a previously described method (3,14). The polypeptide concentration in the medium used for the adsorption process was generally 6.5 ϫ 10 Ϫ6 M. Still unbound surface sites were completely blocked with BSA.…”

Section: Methodsmentioning

confidence: 99%

“…with organized subepithelial lymphoid tissue (5,11). Polypeptides can be transported either presented free in the bathing solution or adsorbed on latex nanospheres (3,4,(6)(7)(8). Observations with this latter system have shown that net transport is selective for the different polypeptides; antibodies are preferred, especially if they are oriented with F c outside and F ab bound specifically to their antigen adsorbed on the bead (6,14).…”

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confidence: 99%

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Further analysis of transcytosis of free polypeptides and polypeptide-coated nanobeads in rabbit nasal mucosa

Cremaschi

Dossena

Porta

et al. 2001

Journal of Applied Physiology

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In rabbit nasal mucosa, free polypeptides and polypeptide-coated nanospheres are actively absorbed by the M cells present in specialized areas of the epithelium. Because polypeptide-coated nanosphere transport was abolished in the presence of free polypeptides, free polypeptides and polypeptide-coated nanospheres are shown here to compete. Fluxes of polypeptide-coated nanospheres with 356, 490, and 548 nm diameters have been compared. BSA-coated beads were poorly transported, at the same rate, when bead diameters were 356 or 490 nm [net flux of approximately 2-2.5 x 10(6) nanospheres (nan). cm(-2) x h(-1)]; however, their net transport largely increased toward a value of 25 x 10(6) nan. cm(-2) x h(-1) at a diameter of 548 nm. Insulin-coated beads displayed a net flux that was significantly higher than BSA-coated beads but equally were transported at the same rate (net flux of approximately 8.0 x 10(6) nan. cm(-2) x h(-1)) at diameters of 356 or 490 nm; once again, their net flux significantly increased toward a value of 25 x 10(6) nan. cm(-2) x h(-1), if the bead diameter was 548 nm. Insulin plus anti-insulin IgG-coated 490-nm-diameter beads displayed a very high net flux, although not yet saturating (approximately 60 x 10(6) nan. cm(-2) x h(-1)); however, a significantly lower saturated net flux (once again approximately 25 x 10(6) nan. cm(-2) x h(-1)) was shown with 548-nm-diameter beads. In conclusion, 1) in the range of 356-490 nm diameter, net transport was independent of bead diameter and, conversely, largely dependent on the coating polypeptides, and 2) at 548 nm diameter, nanospheres tended to be transferred at similar rates independently of coating kind and the maximal net transport capacity of the mucosa was reduced. The suspension viscosity largely increased with 548-nm polypeptide-coated nanospheres; this fact is hypothetically proposed to be the cause of these events.

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“…topical, transdermal, oral, etc. The major transport pathways of particulate system when administered orally are transcellular and paracellular (Cremaschi et al, 1996;Brooking et al, 2001;Illum, 2007). Nanosized particles, i.e.…”

Section: Mechanism Of Transportmentioning

confidence: 99%

Novel drug delivery system: an immense hope for diabetics

et al. 2014

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Context: Existing medication systems for the treatment of diabetes mellitus (DM) are inconvenient and troublesome for effective and safe delivery of drugs to the specific site. Therefore, investigations are desired to deliver antidiabetics using novel delivery approaches followed by their commercialization. Objective: The present review aims to provide a compilation on the latest development in the field of novel drug delivery systems (NDDSs) for antidiabetics with special emphasis on particulate, vesicular and miscellaneous systems. Methods: Review of literature (restricted to English language only) was done using electronic databases like Pubmed Õ and Scirus, i.e. published during [2005][2006][2007][2008][2009][2010][2011][2012][2013]. The CIMS/MIMS India Medical Drug Information eBook was used regarding available marketed formulation of antidiabetic drugs. Keywords used were ''nanoparticle'', ''microparticle'', ''liposomes'', ''niosomes'', ''transdermal systems'', ''insulin'', ''antidiabetic drugs'' and ''novel drug delivery systems''. Single inclusion was made for one article. If in vivo study was not done then article was seldom included in the manuscript. Results: The curiosity to develop NDDSs of antidiabetic drugs with special attention to the nanoparticulate system followed by microparticulate and lipid-based system is found to emerge gradually to overcome the problems associated with the conventional dosage forms and to win the confidence of end users towards the higher acceptability. Conclusion: In the current scientific panorama when the area of novel drug delivery system has been recognized for its palpable benefits, unique potential of providing physical stability, sustained and site-specific drug delivery for a scheduled period of time can open new vistas for precise, safe and quality treatment of DM.

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The active transport of polypeptides in the rabbit nasal mucosa is supported by a specific vesicular transport inhibited by cytochalasin D

Cited by 15 publications

References 10 publications

Translocation of Human Calcitonin in Respiratory Nasal Epithelium Is Associated with Self-Assembly in Lipid Membrane

Translocation of Human Calcitonin in Respiratory Nasal Epithelium Is Associated with Self-Assembly in Lipid Membrane

Further analysis of transcytosis of free polypeptides and polypeptide-coated nanobeads in rabbit nasal mucosa

Novel drug delivery system: an immense hope for diabetics

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