Inhalable Formulation Based on Lipid-Polymer Hybrid Nanoparticles for the Macrophage Targeted Delivery of Roflumilast

Here, novel lipid-polymer hybrid nanoparticles (LPHNPs), targeted to lung macrophages, were realized as potential carriers for Roflumilast administration in the management of chronic obstructive pulmonary disease (COPD). To achieve this, Roflumilast-loaded fluorescent polymeric nanoparticles, based on a polyaspartamide-polycaprolactone graft copolymer, and lipid vesicles, made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-distearoyl-sn-glycero-phosphoethanolamine-N-(polyethylene glycol)-mannose, were properly combined using a two-step method, successfully obtaining Roflumilast-loaded hybrid fluorescent nanoparticles (Man-LPHFNPs@Roflumilast). These exhibit colloidal size and a negative ζ potential, 50 wt % phospholipids, and a core-shell-type morphology; they slowly release the entrapped drug in a simulated physiological fluid. The surface analysis also demonstrated their high surface PEG density, which confers mucus-penetrating properties. Man-LPHFNPs@Roflumilast show high cytocompatibility toward human bronchial epithelium cells and macrophages and are uptaken by the latter through an active mannose-mediated targeting process. To achieve an inhalable formulation, the nano-into-micro strategy was applied, encapsulating Man-LPHFNPs@Roflumilast in poly(vinyl alcohol)/leucine-based microparticles by spray-drying

Preparation and Characterization of Inulin Coated Gold Nanoparticles for Selective Delivery of Doxorubicin to Breast Cancer Cells

A novel folate-targeted gold-based nanosystem for achieving selectivity towards folate receptor (FR) positive cells is proposed, by virtue of the fact that the FR is a molecularly targeted entity overexpressed in a wide spectrum of solid tumors. A new inulin-folate derivative (INU-FA) has been synthesized to act as coating agent for 40 nm gold nanoparticles. The obtained polymer-coated gold nanoparticles (Au@INU-FA) were characterized in terms of hydrodynamic radius, shape, zeta potential, and aqueous stability and were loaded with doxorubicin (Au@INU-FA/Doxo). Its release capability was tested in different release media. The selectivity of Au@INU-FA/Doxo system towards FRs-positive cancer cells was proved by the differences in the quantitative uptake using human breast cancer MCF7 as FR-positive cells and 16HBE epithelial as noncancer cell line. Furthermore, the folate-mediated uptake mechanism was studied by FRs-blocking experiments. On the whole Au@INU-FA/Doxo was able to be preferentially internalized into MCF7 cells proving a folate-mediated endocytosis mechanism which allowed a higher and selective cytotoxic effect towards cancer cells. The cytotoxicity profile was evaluated on both cancer and noncancer cell lines, displaying that folate-mediated targeting implied advantageous therapeutic effects, such as amplified drug uptake and increased anticancer activity towards MCF7 cancer cells

Double-Network-Structured Graphene Oxide-Containing Nanogels as Photothermal Agents for the Treatment of Colorectal Cancer

Here, we reported the production of hyaluronic acid/polyaspartamide-based double-network nanogels for the potential treatment of colorectal carcinoma. Graphene oxide, thanks to the huge aromatic surface area, allows to easily load high amount of irinotecan (33.0% w/w) and confers to the system hyperthermic properties when irradiated with a near-infrared (NIR) laser beam. We demonstrate that the release of antitumor drug is influenced both by the pH of the external medium and the NIR irradiation process. In vitro biological studies, conducted on human colon cancer cells (HCT 116), revealed that nanogels are uptaken by the cancer cells and, in the presence of the antitumor drug, can produce a synergistic hyperthermic/cytotoxic effect. Finally, 3D experiments demonstrate that it is possible to conduct thermal ablation of solid tumors after the intratumoral administration of nanogels

HYDROPHOBIC POLYMER COATED SUPERPARAMAGNETIC NANOPARTICLES FOR ANTICANCER DRUG DELIVERY

HYDROPHOBIC POLYMER COATED SUPERPARAMAGNETI NANOPARTICLES FOR ANTICANCER DRUG DELIVERY LICCIARDI M.1, SCIALABBA C.1, AMATO G.1, CAVALLARO G.1, GIAMMONA G.1,2 1Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari (STEMBIO), University of Palermo, via Archirafi 32, 90123, Palermo, Italy. 2IBF-CNR, via Ugo La Malfa, 153, 90143 Palermo, Italy. Superparamagnetic Fe3O4 nanoparticles have been recently used in drug delivery applications [1-4]. In this study, a novel approach to prepare magnetic polymeric nanoparticles containing superparamagnetic domains and hydrophobic polymeric shell using microemulsion-solvent evaporation method is reported. PHEA-IB-poly(ButMA) copolymer was used as coating copolymer to obtain magnetic nanoparticles by O/W emulsion of polymer solution in the presence of 10 nm Fe3O4 superparamagnetic nanoparticles and the anticancer drug flutamide. Obtained magnetic nanoparticles were characterized by DLS, TEM and magnetometry. The results obtained from TEM (Figure 1) and DLS analysis showed that the particles are spherical with average size of about 250 nm. The magnetic measurement studies revealed the superparamagnetic behavior of the nanoparticles and the presence of superparamagnetic domains inside nanoparticles. Cytotoxicity profile of the nanoparticles on LNCaP cells showed that the flutamide loaded nanoparticles, compared to free flutamide, caused a significant reduction of LNCaP cells proliferation induced by DHT. In vivo biodistribution of drug loaded into nanoparticles in rats subjected to an external magnetic field showed important quantitative differences in comparison with that obtained in the control group. FLU was concentrated most conspicuously in kidney, and less in all the other organs (Figure 2). This modified biodistribution profile demonstrated that these nanoparticles are able to control drug biodistribution by means of an external magnetic field that may attract the nanoparticles in a specific site of the body or organ. Obtained data shows that coated Fe3O4 superparamagnetic nanoparticles are potentially useful for in vivo applications in treatment of tumors. References [1] Adv. Drug Delivery Rev. 16, 321–334, 1995. [2] Radiology 36, 153–163, 1996. [3] J. Microencapsulation,. 13, 245–255, 1996. [4] Life Sci., 44,. 175–186, 1989