Nanopreparations for Oral Administration

Hubbard, Dallin; Brayden, David J.; Ghandehari, Hamidreza

doi:10.1142/9789814520652_0022

Cited by 4 publications

(4 citation statements)

References 206 publications

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“…The 10 mM concentrations, however, did not significantly enhance the mannitol permeability in jejunal segments. Colonic epithelium has been noted for the increased sensitivity to penetration enhancement and this may be the rationale for these results in the presence of PAMAM dendrimers . Factors that may contribute to this enhanced sensitivity may be the heightened ability of colonic tissue to absorb water and electrolytes, which may drag dendrimers into close proximity with epithelial layers and modulate tight junction opening and enhanced mannitol transport.…”

Section: Discussionmentioning

confidence: 97%

“…The permeability of PAMAM dendrimers across intestinal epithelial barrier models has been evaluated in Caco-2 monolayers, ,,− isolated rat intestinal tissue, , in vivo to rats and mice, , and in isolated human tissues as reported here. Of note was the permeability of PAMAM dendrimers ranging from 2.1 × 10 –6 for G3.5 probes in isolated human jejunum.…”

Section: Discussionmentioning

confidence: 99%

“…Colonic epithelium has been noted for the increased sensitivity to penetration enhancement and this may be the rationale for these results in the presence of PAMAM dendrimers. 38 Factors that may contribute to this enhanced sensitivity may be the heightened ability of colonic tissue to absorb water and electrolytes, which may drag dendrimers into close proximity with epithelial layers and modulate tight junction opening and enhanced mannitol transport. The 1 mM and 0.1 mM concentrations of PAMAM dendrimer caused no significant changes in mannitol transport in colonic epithelium.…”

Section: ■ Discussionmentioning

confidence: 99%

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Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue

et al. 2015

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Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2 models innately lack mucous barriers, and rat isolated intestinal tissue has been shown to overestimate human permeability. This study is the first report of transport of PAMAM dendrimers across isolated human intestinal epithelium. It was observed that FITC labeled G4-NH2 and G3.5-COOH PAMAM dendrimers at 1 mM concentration do not have a statistically higher permeability compared to free FITC controls in isolated human jejunum and colonic tissues. Mannitol permeability was increased at 10 mM concentrations of G3.5-COOH and G4-NH2 dendrimers. Significant histological changes in human colonic and jejunal tissues were observed at G3.5-COOH and G4-NH2 concentrations of 10 mM implying that dose limiting toxicity may occur at similar concentrations in vivo. The permeability through human isolated intestinal tissue in this study was compared to previous rat and Caco-2 permeability data. This study implicates that PAMAM dendrimer oral drug delivery may be feasible, but it may be limited to highly potent drugs.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

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Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue

et al. 2015

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“…However, decreased cytocompatibility for both groups was identified since we found that at Day 7, Dermabond and TMC3 had lower DNA concentrations than cells grown on plastic. The toxicity of Dermabond is likely due to cyanoacrylate degradation into cyanoacetate and formaldahyde via the inverse Knoevenagel reaction, but could be due to other metabolic pathways (Hubbard et al , 2014). The reduction of DNA content of cells grown on TMC3 may be due to the buildup of carbonic acid resulting from the release of carbon dioxide after reaction with water (Six and Richter, 2000), or may be due to decreased adhesion.…”

Section: Discussionmentioning

confidence: 99%

In vitro and biomechanical screening of polyethylene glycol and poly(trimethylene carbonate) block copolymers for annulus fibrosus repair

Long

Rotman

Hom

et al. 2017

J Tissue Eng Regen Med

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Abstract:Herniated intervertebral discs are a common cause of back and neck pain. There is an unmet clinical need to seal annulus fibrosus (AF) defects, since discectomy surgeries address acute pain but are complicated by reherniation and recurrent pain.Copolymers of polyethylene glycol with trimethylene carbonate (TMC) and hexamathylene diisocyanate end-groups were formulated as AF sealants since the hexamathylene diisocyanate form covalent bonds with native AF tissue. TMC adhesives were evaluated and optimized using the design criteria: stable size, strong adherence to AF tissue, high cytocompatibility, restoration of intervertebral disc biomechanics to intact levels following in situ repair, and low extrusion risk. TMC adhesives had high adhesion strength as assessed with a pushout test (150 kPa), and low degradation rates over three weeks in vitro. Both TMC adhesives had shear moduli (220 & 490kPa) similar to, but somewhat higher than AF tissue. The adhesive with three TMC moieties per branch (TMC3) was selected for additional in situ testing because it best matched AF shear properties. TMC3 restored torsional stiffness, torsional hysteresis area and axial range of motion to intact states.However, in a failure test of compressive deformation under fixed 5° flexion, some herniation risk was observed with failure strength of 5.9 MPa compared to 13.5 MPa for intact samples; TMC3 herniated under cyclic organ culture testing. These TMC adhesives performed well during in vitro and in situ testing, but additional optimization to enhance failure strength is required to further this material to advanced screening tests such as long term degradation.

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Clinical advances of nanocarrier-based cancer therapy and diagnostics

Luque-Michel

Imbuluzqueta

Sebastián

et al. 2016

Expert Opinion on Drug Delivery

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Cancer is a leading cause of death worldwide and efficient new strategies are urgently needed to combat its high mortality and morbidity statistics. Fortunately, over the years, nanotechnology has evolved as a frontrunner in the areas of imaging, diagnostics and therapy, giving the possibility of monitoring, evaluating and individualizing cancer treatments in real-time. Areas covered: Polymer-based nanocarriers have been extensively studied to maximize cancer treatment efficacy and minimize the adverse effects of standard therapeutics. Regarding diagnosis, nanomaterials like quantum dots, iron oxide nanoparticles or gold nanoparticles have been developed to provide rapid, sensitive detection of cancer and, therefore, facilitate early treatment and monitoring of the disease. Therefore, multifunctional nanosystems with both imaging and therapy functionalities bring us a step closer to delivering precision/personalized medicine in the cancer setting. Expert opinion: There are multiple barriers for these new nanosystems to enter the clinic, but it is expected that in the near future, nanocarriers, together with new 'targeted drugs', could replace our current treatments and cancer could become a nonfatal disease with good recovery rates. Joint efforts between scientists, clinicians, the pharmaceutical industry and legislative bodies are needed to bring to fruition the application of nanosystems in the clinical management of cancer.

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Nanopreparations for Oral Administration

Cited by 4 publications

References 206 publications

Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue

Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue

In vitro and biomechanical screening of polyethylene glycol and poly(trimethylene carbonate) block copolymers for annulus fibrosus repair

Clinical advances of nanocarrier-based cancer therapy and diagnostics

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