17 research outputs found
Polyphosphoramidates That Undergo Acid-Triggered Backbone Degradation
The
direct and facile synthesis of polyphosphoramidates (PPAs)
with acid-labile phosphoramidate backbone linkages are reported, together
with demonstration of their hydrolytic degradability, evaluated under
acidic conditions. The introduction of acid-labile linkages along
the polymer backbone led to rapid degradation of the polymer backbone
dependent upon the environmental stimuli. An oxazaphospholidine monomer
bearing a phosphoramidate linkage was designed and synthesized to
afford the PPAs via organobase-catalyzed ring-opening polymerization
in a controlled manner. The hydrolytic degradation of the PPAs was
studied, revealing breakdown of the polymer backbone through cleavage
of the phosphoramidate linkages under acidic conditions
Emplacement of the Aya Variscan granitic pluton (Basque Pyrenees) in a dextral transcurrent regime inferred from a combined magneto-structural and gravimetric study
Improving Paclitaxel Delivery: In Vitro and In Vivo Characterization of PEGylated Polyphosphoester-Based Nanocarriers
Nanomaterials have great potential to offer effective treatment against devastating diseases by providing sustained release of high concentrations of therapeutic agents locally, especially when the route of administration allows for direct access to the diseased tissues. Biodegradable polyphosphoester-based polymeric micelles and shell cross-linked knedel-like nanoparticles (SCKs) have been designed from amphiphilic block-graft terpolymers, PEBP-b-PBYP-g-PEG, which effectively incorporate high concentrations of paclitaxel (PTX). Well-dispersed nanoparticles physically loaded with PTX were prepared, exhibiting desirable physiochemical characteristics. Encapsulation of 10 wt% PTX, into either micelles or SCKs, allowed for aqueous suspension of PTX at concentrations up to 4.8 mg/mL, as compared to <2.0 mu g/mL for the aqueous solubility of the drug alone. Drug release studies indicated that PTX released from these nanostructures was defined through a structure-function relationship, whereby the half-life of sustained PTX release was doubled through cross-linking of the micellar structure to form SCKs. In vitro, physically loaded micellar and SCK nanotherapeutics demonstrated IC50 values against osteosarcoma cell lines, known to metastasize to the lungs (CCH-OS-O and SJSA), similar to the pharmaceutical Taxol formulation. Evaluation of these materials in vivo has provided an understanding of the effects of nanoparticle structurefunction relationships on intratracheal delivery and related biodistribution and pharmacokinetics. Overall, we have demonstrated the potential of these novel nanotherapeutics toward future sustained release treatments via administration directly to the sites of lung metastases of osteosarcoma
Integrated equation to evaluate accumulation profiles of drugs eliminated by Michaelis-Menten kinetics
Change of trunk sap flow of Ginkgo biloba L. and its response to inhibiting transpiration treatment
Improving Paclitaxel Delivery: <i>In Vitro</i> and <i>In Vivo</i> Characterization of PEGylated Polyphosphoester-Based Nanocarriers
Nanomaterials have great potential
to offer effective treatment
against devastating diseases by providing sustained release of high
concentrations of therapeutic agents locally, especially when the
route of administration allows for direct access to the diseased tissues.
Biodegradable polyphosphoester-based polymeric micelles and shell
cross-linked knedel-like nanoparticles (SCKs) have been designed from
amphiphilic block-graft terpolymers, PEBP-<i>b</i>-PBYP-<i>g</i>-PEG, which effectively incorporate high concentrations
of paclitaxel (PTX). Well-dispersed nanoparticles physically loaded
with PTX were prepared, exhibiting desirable physiochemical characteristics.
Encapsulation of 10 wt% PTX, into either micelles or SCKs, allowed
for aqueous suspension of PTX at concentrations up to 4.8 mg/mL, as
compared to <2.0 μg/mL for the aqueous solubility of the
drug alone. Drug release studies indicated that PTX released from
these nanostructures was defined through a structure–function
relationship, whereby the half-life of sustained PTX release was doubled
through cross-linking of the micellar structure to form SCKs. <i>In vitro</i>, physically loaded micellar and SCK nanotherapeutics
demonstrated IC<sub>50</sub> values against osteosarcoma cell lines,
known to metastasize to the lungs (CCH-OS-O and SJSA), similar to
the pharmaceutical Taxol formulation. Evaluation of these materials <i>in vivo</i> has provided an understanding of the effects of
nanoparticle structure–function relationships on intratracheal
delivery and related biodistribution and pharmacokinetics. Overall,
we have demonstrated the potential of these novel nanotherapeutics
toward future sustained release treatments via administration directly
to the sites of lung metastases of osteosarcoma