4 research outputs found
Medication use in adults with attention deficit/hyperactivity disorder in a commercially-insured population in the United States
<p><b>Objective:</b> To examine real-world prescription medication usage among commercially-insured adults with attention deficit/hyperactivity disorder (ADHD) in the US.</p> <p><b>Methods:</b> Adults with ADHD who received ≥1 ADHD medication during 2013 were identified from a large US claims database. Combination therapy was defined as an overlap of ≥30 days between the index (first treatment ≥30 days in 2013) and another medication(s). Patients were classified into six groups: long-acting (LA) monotherapy, short-acting (SA) monotherapy, LA + LA, SA + SA, LA + SA, and >2 therapies. Analyses compared baseline characteristics by regimen, ranked combination regimens, and estimated daily average consumption (DACON) for monotherapy users.</p> <p><b>Results:</b> Of 206,443 adults with ADHD (mean age = 32.9 years; 51.6% female), 56.9% used LA monotherapy, 30.7% SA monotherapy, and 12.5% used combination therapies (LA + SA: 10.3%; LA + LA: 1.3%; SA + SA: 0.4%; >2 therapies: 0.5%). Extended-release mixed amphetamine salts (MAS-XR, 39.2%) and lisdexamfetamine (LDX, 31.5%) were the most common LA monotherapies. Nearly all SA monotherapy patients received immediate-release mixed amphetamine salts (MAS-IR; 81.7%). The top three therapies among combination categories were: (a) LA + LA: branded MAS-XR + generic MAS-XR (13.7%), LDX + generic MAS-XR (10.8%), LDX + guanfacine ER (10.7%); (b) SA + SA: generic MAS-IR + clonidine IR (33.5%), generic MAS-IR + generic MPH SA (17.9%), branded MAS-IR + generic MAS-IR (11.1%); (c) LA + SA: generic MAS-XR+/-IR (39.2%), LDX + generic MAS-IR (16.7%), LA + SA generic MPH (12.6%). Among monotherapy users, DACON was 1.2 ± 0.6 (LA) and 2.1 ± 0.9 (SA) tablets.</p> <p><b>Conclusions:</b> There is significant treatment heterogeneity among US adults with ADHD. A sizable proportion of patients received monotherapies at above the recommended dosages or combination therapies, suggesting existing single-tablet regimens may not meet patients’ needs.</p
Quantitation of Complexed versus Free Polymers in Interpolyelectrolyte Polyplex Formulations
The
quantity of free polymer in a polymer/DNA complex (polyplex)
formulation critically impacts its gene transfection efficiency, cellular
uptake, and toxicity. In this study, the compositions of three interpolyelectrolyte
polyplex formulations were quantified by a facile NMR method. Using
careful integration of a 1D <sup>1</sup>H NMR spectrum with a broad
spectral width, the quantities of unbound polymer and polyplexes in
solution were determined. Linear polyethyleneimine (PEI) mixed with
DNA at polymer amine to DNA phosphate molar ratio (N/P ratio) of 5
revealed an effective binding N/P ratio of 3.5 without excess free
polymer. This result is in strong agreement with the stoichiometric
number of PEI/DNA binding obtained by isothermal titration calorimetry.
The noninvasive nature of this method allows broad application to
a range of polyelectrolyte coacervates, opening new opportunities
for understanding and optimizing polyelectrolyte complex formation
and providing quantitation of complex formation in a single measurement
Indocyanine Green-Loaded Nanoparticles for Image-Guided Tumor Surgery
Detecting
positive tumor margins and local malignant masses during
surgery is critical for long-term patient survival. The use of image-guided
surgery for tumor removal, particularly with near-infrared fluorescent
imaging, is a potential method to facilitate removing all neoplastic
tissue at the surgical site. In this study we demonstrate a series
of hyaluronic acid (HLA)-derived nanoparticles that entrap the near-infrared
dye indocyanine green, termed NanoICG, for improved delivery of the
dye to tumors. Self-assembly of the nanoparticles was driven by conjugation
of one of three hydrophobic moieties: aminopropyl-1-pyrenebutanamide
(PBA), aminopropyl-5β-cholanamide (5βCA), or octadecylamine
(ODA). Nanoparticle self-assembly, dye loading, and optical properties
were characterized. NanoICG exhibited quenched fluorescence that could
be activated by disassembly in a mixed solvent. NanoICG was found
to be nontoxic at physiologically relevant concentrations and exposure
was not found to inhibit cell growth. Using an MDA-MB-231 tumor xenograft
model in mice, strong fluorescence enhancement in tumors was observed
with NanoICG using a fluorescence image-guided surgery system and
a whole-animal imaging system. Tumor contrast with NanoICG was significantly
higher than with ICG alone
Development of a Self-Assembled Nanoparticle Formulation of Orlistat, Nano-ORL, with Increased Cytotoxicity against Human Tumor Cell Lines
Fatty acid synthase (FASN), the enzyme
that catalyzes <i>de
novo</i> synthesis of fatty acids, is expressed in many cancer
types. Its potential as a therapeutic target is well recognized, but
inhibitors of FASN have not yet been approved for cancer therapy.
Orlistat (ORL), an FDA-approved lipase inhibitor, is also an effective
inhibitor of FASN. However, ORL is extremely hydrophobic and has low
systemic uptake after oral administration. Thus, new strategies are
required to formulate ORL for cancer treatment as a FASN inhibitor.
Here, we report the development of a nanoparticle (NP) formulation
of ORL using amphiphilic bioconjugates that are derived from hyaluronic
acid (HA), termed Nano-ORL. The NPs were loaded with up to 20 wt %
weight of ORL at greater than 95% efficiency. The direct inhibition
of the human recombinant thioesterase domain of FASN by ORL extracted
from Nano-ORL was similar to that of stock ORL. Nano-ORL demonstrated
a similar ability to inhibit cellular FASN activity when compared
to free ORL, as demonstrated by analysis of <sup>14</sup>C-acetate
incorporation into lipids. Nano-ORL treatment also disrupted mitochondrial
function similarly to ORL by reducing adenosine triphosphate turnover
in MDA-MB-231 and LNCaP cells. Nano-ORL demonstrated increased potency
compared to ORL toward prostate and breast cancer cells. Nano-ORL
decreased viability of human prostate and breast cancer cell lines
to 55 and 57%, respectively, while free ORL decreased viability to
71 and 79% in the same cell lines. Moreover, Nano-ORL retained cytotoxic
activity after a 24 h preincubation in aqueous conditions. Preincubation
of ORL dramatically reduced the efficacy of ORL as indicated by high
cell viability (>85%) in both breast and prostate cell lines. These
data demonstrate that NP formulation of ORL using HA-derived polymers
retains similar levels of FASN, lipid synthesis, and ATP turnover
inhibition while significantly improving the cytotoxic activity against
cancer cell lines