11 research outputs found
Cream Formulation Impact on Topical Administration of Engineered Colloidal Nanoparticles
In order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide) nanoparticles (MNP) coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP) cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics
Cytofluorimetric analysis showing PMNP nanoparticles uptake by mouse skin and lymph node cells.
<p>PMNP suspension (a, upper panels). Skin CD45-positive and negative cells showing CFSE incorporation. Note that most of the skin cells uptake PMNP nanoparticles administered with the cream formulation. (a, lower panels) CFSE-positive cells in the lymph nodes of mice that received PMNP nanoparticles via cream formulation or via sc administration. Note that only with sc PMNP administration, nanoparticle-positive cells can be detected in the draining lymph nodes. (b) Lymph node macrophages and dendritic cells, identified as CD11b- and CD11c-positive cells respectively, showing CFSE incorporation. Note that only when PMNP are administered sc, CFSE positive macrophages and dendritic cells can be detected in the lymph nodes.</p
Fe<sub>3</sub>O<sub>4</sub> nanoparticles (MNP, a) synthesized in organic solvent and transferred to a water solution using PMA amphiphilic polymer (PMNP, b).
<p>MNP and PMNP were highly monodisperse in size as it is shown by TEM images (scale bars = 40 nm,). Part of the highly concentrated PMNP suspension (8 mg mL<sup>â1</sup>) was incorporated in a w/o cream (0.8 wt % concentration) (c).</p
Histological microphotograph of normal human skin section.
<p>Haematoxylin and eosin staining (original magnification 40Ă) (a). <i>In vitro</i> diffusion studies of PMNP colloidal suspension or cream in human skin were carried out using Franz diffusion cells and diffused PMNP were quantified by ICP-OES analysis (b).</p
Fates of nanoparticles depending on the route of skin administration.
<p>Nanoparticle administered in a cream formulation are taken up by all the skin cell types and do no reach the draining lymph nodes. Nanoparticle administered with a sc injection in aqueous suspension are efficiently transported to the draining lymph nodes.</p
Antiproliferative Effect of ASC-J9 Delivered by PLGA Nanoparticles against Estrogen-Dependent Breast Cancer Cells
Among polymeric nanoparticles designed
for cancer therapy, PLGA
nanoparticles have become one of the most popular polymeric devices
for chemotherapeutic-based nanoformulations against several kinds
of malignant diseases. Promising properties, including long-circulation
time, enhanced tumor localization, interference with âmultidrugâ
resistance effects, and environmental biodegradability, often result
in an improvement of the drug bioavailability and effectiveness. In
the present work, we have synthesized 1,7-bisÂ(3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one
(ASC-J9) and developed uniform ASC-J9-loaded PLGA nanoparticles of
about 120 nm, which have been prepared by a single-emulsion process.
Structural and morphological features of the nanoformulation were
analyzed, followed by an accurate evaluation of the <i>in vitro</i> drug release kinetics, which exhibited Fickian law diffusion over
10 days. The intracellular degradation of ASC-J9-bearing nanoparticles
within estrogen-dependent MCF-7 breast cancer cells was correlated
to a time- and dose-dependent activity of the released drug. A cellular
growth inhibition associated with a specific cell cycle G2/M blocking
effect caused by ASC-J9 release inside the cytosol allowed us to put
forward a hypothesis on the action mechanism of this nanosystem, which
led to the final cell apoptosis. Our study was accomplished using
Annexin V-based cell death analysis, MTT assessment of proliferation,
radical scavenging activity, and intracellular ROS evaluation. Moreover,
the intracellular localization of nanoformulated ASC-J9 was confirmed
by a Raman optical imaging experiment designed <i>ad hoc</i>. PLGA nanoparticles and ASC-J9 proved also to be safe for a healthy
embryo fibroblast cell line (3T3-L1), suggesting a possible clinical
translation of this potential nanochemotherapeutic to expand the inherently
poor bioavailability of hydrophobic ASC-J9 that could be proposed
for the treatment of malignant breast cancer