Special Issue "Pharmaceutical Nanotechnology"

A special issue of Nanomaterials (ISSN 2079-4991).

Deadline for manuscript submissions: 31 October 2018

Special Issue Editors

Guest Editor
Prof. Dr. Fabio Sonvico

Univ Parma, Interdept Ctr Biopharmanet TEC, Parco Area Sci 27-A, I-43124 Parma, Italy
Website | E-Mail
Interests: pharmaceutical nanotechnology; nasal delivery; brain delivery; lung cancer; polysaccharides
Guest Editor
Prof. Dr. Erem Bilensoy

Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
Website | E-Mail
Interests: Tumor targeted nanoparticles; Cyclodextrin based nanocarriers (nanoparticles, nanocapsules, nanofibers, hydronanogels); Amphiphilic cyclodextrins ; Cationic nanoparticulate drug delivery systems; Wound healing; Bioavailability enhancement through cyclodextrin complexation; Inkjet and 3D printed drug delivery systems
Guest Editor
Prof. Dr. Adriana Raffin Pohlmann

Organic Chemistry at the Chemistry Institute of the Universidade Federal do Rio Grande do Sul in Porto Alegre, Brazil
Website | E-Mail
Interests: Organic chemistry applied to drug nanocarriers, including polymeric nanocapsules and nanospheres

Special Issue Information

Dear Colleagues,

Pharmaceutical nanotechnologies, over the past twenty years, have shown great potential for drug delivery due to their unique biopharmaceutical properties. The first breakthrough applications were related to the intravenous administration of anticancer drugs, loaded liposomes, opening the possibility to target tumor parenchyma via the enhanced-permeability and retention effect. However, more recently, the development of manufactured nanocarriers, starting from different materials, and with more or less complex surface modifications, has widened the possibilities of drug-loaded nanoparticles, allowing for administration via different administration routes, stimuli or environment responsive drug delivery, active targeting of organs or specific cells and multiple actions, as in the case of theranostics.

This Special Issue of Nanomaterials will attempt to cover recent advances in Pharmaceutical Nanotechnologies for drug delivery, including biodegradable, surface-modified, stimuli-responsive or targeted nanoparticles, liposomes, and micelles designed for parenteral or non-parenteral administration routes.

Prof. Dr. Fabio Sonvico
Prof. Dr. Erem Bilensoy
Prof. Dr. Adriana Raffin Pohlmann
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nanomaterials is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Nanoparticles
  • liposomes
  • micelles
  • biocompatible
  • biodegradable
  • stimuli-responsive
  • targeting
  • parenteral administration
  • oral delivery
  • nasal delivery
  • pulmonary delivery
  • topical delivery

Published Papers (14 papers)

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Research

Jump to: Review

Open AccessArticle Development and Characterization of Solid Lipid Nanoparticles Loaded with a Highly Active Doxorubicin Derivative
Nanomaterials 2018, 8(2), 110; doi:10.3390/nano8020110
Received: 10 January 2018 / Revised: 9 February 2018 / Accepted: 13 February 2018 / Published: 16 February 2018
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Abstract
Solid lipid nanoparticles (SLNs) comprise a versatile drug delivery system that has been developed for the treatment of a variety of diseases. The present study will investigate the feasibility of entrapping an active doxorubicin prodrug (a squalenoyl-derivative) in SLNs. The doxorubicin derivative-loaded SLNs
[...] Read more.
Solid lipid nanoparticles (SLNs) comprise a versatile drug delivery system that has been developed for the treatment of a variety of diseases. The present study will investigate the feasibility of entrapping an active doxorubicin prodrug (a squalenoyl-derivative) in SLNs. The doxorubicin derivative-loaded SLNs are spherically shaped, have a mean diameter of 300–400 nm and show 85% w/w drug entrapment efficiency. The effects on cell growth of loaded SLNs, free doxorubicin and the prodrug have been examined using cytotoxicity and colony-forming assays in both human ovarian cancer line A2780 wild-type and doxorubicin-resistant cells. Further assessments as to the treatment’s ability to induce cell death by apoptosis have been carried out by analyzing annexin-V staining and the activation of caspase-3. The in vitro data demonstrate that the delivery of the squalenoyl-doxorubicin derivative by SLNs increases its cytotoxic activity, as well as its apoptosis effect. This effect was particularly evident in doxorubicin-resistant cells. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Open AccessArticle Determination of Non-Transferrin Bound Iron, Transferrin Bound Iron, Drug Bound Iron and Total Iron in Serum in a Rats after IV Administration of Sodium Ferric Gluconate Complex by Simple Ultrafiltration Inductively Coupled Plasma Mass Spectrometric Detection
Nanomaterials 2018, 8(2), 101; doi:10.3390/nano8020101
Received: 13 December 2017 / Revised: 25 January 2018 / Accepted: 8 February 2018 / Published: 11 February 2018
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Abstract
A rapid, sensitive and specific ultrafiltration inductively-coupled plasma mass spectrometry method was developed and validated for the quantification of non-transferrin bound iron (NTBI), transferrin bound iron (TBI), drug bound iron (DI) and total iron (TI) in the same rat serum sample after intravenous
[...] Read more.
A rapid, sensitive and specific ultrafiltration inductively-coupled plasma mass spectrometry method was developed and validated for the quantification of non-transferrin bound iron (NTBI), transferrin bound iron (TBI), drug bound iron (DI) and total iron (TI) in the same rat serum sample after intravenous (IV) administration of iron gluconate nanoparticles in sucrose solution (Ferrlecit®). Ultrafiltration with a 30 kDa molecular cut-off filter was used for sample cleanup. Different elution solvents were used to separate each form of iron from sample serum. Isolated fractions were subjected to inductively-coupled mass spectrometric analysis after microwave digestion in 4% nitric acid. The reproducibility of the method was evaluated by precision and accuracy. The calibration curve demonstrated linearity from 5–500 ng/mL with a regression (r2) of more than 0.998. This method was effectively implemented to quantify rat pharmacokinetic study samples after intravenous administration of Ferrlecit®. The method was successfully applied to a pharmacokinetic (PK) study of Ferrlecit in rats. The colloidal iron followed first order kinetics with half-life of 2.2 h and reached background or pre-dose levels after 12 h post-dosing. The drug shown a clearance of 0.31 mL/min/kg and volume of distribution of 0.05 L/kg. 19.4 ± 2.4 mL/h/kg. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Open AccessArticle An Inhalable Powder Formulation Based on Micro- and Nanoparticles Containing 5-Fluorouracil for the Treatment of Metastatic Melanoma
Nanomaterials 2018, 8(2), 75; doi:10.3390/nano8020075
Received: 27 December 2017 / Revised: 19 January 2018 / Accepted: 22 January 2018 / Published: 30 January 2018
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Abstract
Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil
[...] Read more.
Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil (5FU) for pulmonary administration, aiming at local and systemic action. Therefore, two innovative inhalable powder formulations were produced by spray-drying using chondroitin sulfate as a structuring polymer: (a) 5FU nanoparticles obtained by piezoelectric atomization (5FU-NS) and (b) 5FU microparticles of the mucoadhesive agent Methocel™ F4M for sustained release produced by conventional spray drying (5FU-MS). The physicochemical and aerodynamic were evaluated in vitro for both systems, proving to be attractive for pulmonary delivery. The theoretical aerodynamic diameters obtained were 0.322 ± 0.07 µm (5FU-NS) and 1.138 ± 0.54 µm (5FU-MS). The fraction of respirable particles (FR%) were 76.84 ± 0.07% (5FU-NS) and 55.01 ± 2.91% (5FU-MS). The in vitro mucoadhesive properties exhibited significant adhesion efficiency in the presence of Methocel™ F4M. 5FU-MS and 5FU-NS were tested for their cytotoxic action on melanoma cancer cells (A2058 and A375) and both showed a cytotoxic effect similar to 5FU pure at concentrations of 4.3 and 1.7-fold lower, respectively. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Open AccessArticle Cellular Interaction and Tumoral Penetration Properties of Cyclodextrin Nanoparticles on 3D Breast Tumor Model
Nanomaterials 2018, 8(2), 67; doi:10.3390/nano8020067
Received: 1 December 2017 / Revised: 18 December 2017 / Accepted: 2 January 2018 / Published: 26 January 2018
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Abstract
Amphiphilic cyclodextrins are biocompatible oligosaccharides that can be used for drug delivery especially for the delivery of drugs with solubility problems thanks to their unique molecular structures. In this paper, Paclitaxel was used as a model anticancer drug to determine the inclusion complex
[...] Read more.
Amphiphilic cyclodextrins are biocompatible oligosaccharides that can be used for drug delivery especially for the delivery of drugs with solubility problems thanks to their unique molecular structures. In this paper, Paclitaxel was used as a model anticancer drug to determine the inclusion complex properties of amphiphilic cyclodextrins with different surface charge. Paclitaxel-loaded cyclodextrin nanoparticles were characterized in terms of mean particle diameter, zeta potential, encapsulation efficacy, drug release profile and cell culture studies. It was determined that the nanoparticles prepared from the inclusion complex according to characterization studies have a longer release profile than the conventionally prepared nanoparticles. In order to mimic the tumor microenvironment, breast cancer cells and healthy fibroblast cells were used in 3-dimensional (3D) cell culture studies. It was determined that the activities of nanoparticles prepared by conventional methods behave differently in 2-dimensional (2D) and 3D cell cultures. In addition, it was observed that the nanoparticles prepared from the inclusion complex have a stronger anti-tumoral activity in the 3D multicellular tumor model than the drug solution. Furthermore, polycationic amphiphilic cyclodextrin nanoparticles can diffuse and penetrate through multilayer cells in a 3D tumor model, which is crucial for an eventual antitumor effect. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Open AccessArticle Comparative Evaluation of U.S. Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection: Physicochemical Characterization
Nanomaterials 2018, 8(1), 25; doi:10.3390/nano8010025
Received: 23 October 2017 / Revised: 18 December 2017 / Accepted: 20 December 2017 / Published: 5 January 2018
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Abstract
The objective of this study was to evaluate physicochemical equivalence between brand (i.e., Ferrlecit) and generic sodium ferric gluconate (SFG) in sucrose injection by conducting a series of comparative in vitro characterizations using advanced analytical techniques. The elemental iron and carbon content, thermal
[...] Read more.
The objective of this study was to evaluate physicochemical equivalence between brand (i.e., Ferrlecit) and generic sodium ferric gluconate (SFG) in sucrose injection by conducting a series of comparative in vitro characterizations using advanced analytical techniques. The elemental iron and carbon content, thermal properties, viscosity, particle size, zeta potential, sedimentation coefficient, and molecular weight were determined. There was no noticeable difference between brand and generic SFG in sucrose injection for the above physical parameters evaluated, except for the sedimentation coefficient determined by sedimentation velocity analytical ultracentrifugation (SV-AUC) and molecular weight by asymmetric field flow fractionation-multi-angle light scattering (AFFF-MALS). In addition, brand and generic SFG complex products showed comparable molecular weight distributions when determined by gel permeation chromatography (GPC). The observed minor differences between brand and generic SFG, such as sedimentation coefficient, do not impact their biological activities in separate studies of in vitro cellular uptake and rat biodistribution. Coupled with the ongoing clinical study comparing the labile iron level in healthy volunteers, the FDA-funded post-market studies intended to illustrate comprehensive surveillance efforts ensuring safety and efficacy profiles of generic SFG complex in sucrose injection, and also to shed new light on the approval standards on generic parenteral iron colloidal products. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Open AccessArticle Enhanced and Selective Antiproliferative Activity of Methotrexate-Functionalized-Nanocapsules to Human Breast Cancer Cells (MCF-7)
Nanomaterials 2018, 8(1), 24; doi:10.3390/nano8010024
Received: 3 November 2017 / Revised: 21 December 2017 / Accepted: 28 December 2017 / Published: 4 January 2018
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Abstract
Methotrexate is a folic acid antagonist and its incorporation into nanoformulations is a promising strategy to increase the drug antiproliferative effect on human breast cancer cells by overexpressing folate receptors. To evaluate the efficiency and selectivity of nanoformulations containing methotrexate and its diethyl
[...] Read more.
Methotrexate is a folic acid antagonist and its incorporation into nanoformulations is a promising strategy to increase the drug antiproliferative effect on human breast cancer cells by overexpressing folate receptors. To evaluate the efficiency and selectivity of nanoformulations containing methotrexate and its diethyl ester derivative, using two mechanisms of drug incorporation (encapsulation and surface functionalization) in the in vitro cellular uptake and antiproliferative activity in non-tumoral immortalized human keratinocytes (HaCaT) and in human breast carcinoma cells (MCF-7). Methotrexate and its diethyl ester derivative were incorporated into multiwall lipid-core nanocapsules with hydrodynamic diameters lower than 160 nm and higher drug incorporation efficiency. The nanoformulations were applied to semiconfluent HaCaT or MCF-7 cells. After 24 h, the nanocapsules were internalized into HaCaT and MCF-7 cells; however, no significant difference was observed between the nanoformulations in HaCaT (low expression of folate receptors), while they showed significantly higher cellular uptakes than the blank-nanoformulation in MCF-7, which was the highest uptakes observed for the drug functionalized-nanocapsules. No antiproliferative activity was observed in HaCaT culture, whereas drug-containing nanoformulations showed antiproliferative activity against MCF-7 cells. The effect was higher for drug-surface functionalized nanocapsules. In conclusion, methotrexate-functionalized-nanocapsules showed enhanced and selective antiproliferative activity to human breast cancer cells (MCF-7) being promising products for further in vivo pre-clinical evaluations. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Open AccessArticle Comparative Evaluation of U.S. Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection: Biodistribution after Intravenous Dosing in Rats
Nanomaterials 2018, 8(1), 10; doi:10.3390/nano8010010
Received: 29 November 2017 / Revised: 21 December 2017 / Accepted: 23 December 2017 / Published: 28 December 2017
Cited by 3 | PDF Full-text (2868 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Relative biodistribution of FDA-approved innovator and generic sodium ferric gluconate (SFG) drug products was investigated to identify differences in tissue distribution of iron after intravenous dosing to rats. Three equal cohorts of 42 male Sprague-Dawley rats were created with each cohort receiving one
[...] Read more.
Relative biodistribution of FDA-approved innovator and generic sodium ferric gluconate (SFG) drug products was investigated to identify differences in tissue distribution of iron after intravenous dosing to rats. Three equal cohorts of 42 male Sprague-Dawley rats were created with each cohort receiving one of three treatments: (1) the innovator SFG product dosed intravenously at a concentration of 40 mg/kg; (2) the generic SFG product dosed intravenously at a concentration of 40 mg/kg; (3) saline dosed intravenously at equivalent volume to SFG products. Sampling time points were 15 min, 1 h, 8 h, 1 week, two weeks, four weeks, and six weeks post-treatment. Six rats from each group were sacrificed at each time point. Serum, femoral bone marrow, lungs, brain, heart, kidneys, liver, and spleen were harvested and evaluated for total iron concentration by ICP-MS. The ICP-MS analytical method was validated with linearity, range, accuracy, and precision. Results were determined for mean iron concentrations (µg/g) and mean total iron (whole tissue) content (µg/tissue) for each tissue of all groups at each time point. A percent of total distribution to each tissue was calculated for both products. At any given time point, the overall percent iron concentration distribution did not vary between the two SFG drugs by more than 7% in any tissue. Overall, this study demonstrated similar tissue biodistribution for the two SFG products in the examined tissues. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Open AccessArticle Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells
Nanomaterials 2018, 8(1), 2; doi:10.3390/nano8010002
Received: 24 November 2017 / Revised: 14 December 2017 / Accepted: 16 December 2017 / Published: 22 December 2017
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Abstract
Doxorubicin (Dox) clinical use is limited by dose-related cardiomyopathy, becoming more prevalent with increasing cumulative doses. Previously, we developed Dox-loaded lipid-core nanocapsules (Dox-LNC) and, in this study, we hypothesized that self-assembling and interfacial reactions could be used to obtain arginylglycylaspartic acid (RGD)-surface-functionalized-Dox-LNC, which
[...] Read more.
Doxorubicin (Dox) clinical use is limited by dose-related cardiomyopathy, becoming more prevalent with increasing cumulative doses. Previously, we developed Dox-loaded lipid-core nanocapsules (Dox-LNC) and, in this study, we hypothesized that self-assembling and interfacial reactions could be used to obtain arginylglycylaspartic acid (RGD)-surface-functionalized-Dox-LNC, which could target tumoral cells overexpressing αvβ3 integrin. Human breast adenocarcinoma cell line (MCF-7) and human glioblastoma astrocytoma (U87MG) expressing different levels of αvβ3 integrin were studied. RGD-functionalized Dox-LNC were prepared with Dox at 100 and 500 mg·mL−1 (RGD-MCMN (Dox100) and RGD-MCMN (Dox500)). Blank formulation (RGD-MCMN) had z-average diameter of 162 ± 6 nm, polydispersity index of 0.11 ± 0.04, zeta potential of +13.2 ± 1.9 mV and (6.2 ± 1.1) × 1011 particles mL−1, while RGD-MCMN (Dox100) and RGD-MCMN (Dox500) showed respectively 146 ± 20 and 215 ± 25 nm, 0.10 ± 0.01 and 0.09 ± 0.03, +13.8 ± 2.3 and +16.4 ± 1.5 mV and (6.9 ± 0.6) × 1011 and (6.1 ± 1.0) × 1011 particles mL−1. RGD complexation was 7.73 × 104 molecules per nanocapsule and Dox loading were 1.51 × 104 and 7.64 × 104 molecules per nanocapsule, respectively. RGD-functionalized nanocapsules had an improved uptake capacity by U87MG cells. Pareto chart showed that the cell viability was mainly affected by the Dox concentration and the period of treatment in both MCF-7 and U87MG. The influence of RGD-functionalization on cell viability was a determinant factor exclusively to U87MG. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Open AccessArticle Comparative Evaluation of U.S. Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection: In Vitro Cellular Uptake
Nanomaterials 2017, 7(12), 451; doi:10.3390/nano7120451
Received: 8 November 2017 / Revised: 6 December 2017 / Accepted: 11 December 2017 / Published: 15 December 2017
Cited by 2 | PDF Full-text (7499 KB) | HTML Full-text | XML Full-text
Abstract
Iron deficiency anemia is a common clinical consequence for people who suffer from chronic kidney disease, especially those requiring dialysis. Intravenous (IV) iron therapy is a widely accepted safe and efficacious treatment for iron deficiency anemia. Numerous IV iron drugs have been approved
[...] Read more.
Iron deficiency anemia is a common clinical consequence for people who suffer from chronic kidney disease, especially those requiring dialysis. Intravenous (IV) iron therapy is a widely accepted safe and efficacious treatment for iron deficiency anemia. Numerous IV iron drugs have been approved by U.S. Food and Drug Administration (FDA), including a single generic product, sodium ferric gluconate complex in sucrose. In this study, we compared the cellular iron uptake profiles of the brand (Ferrlecit®) and generic sodium ferric gluconate (SFG) products. We used a colorimetric assay to examine the amount of iron uptake by three human macrophage cell lines. This is the first published study to provide a parallel evaluation of the cellular uptake of a brand and a generic IV iron drug in a mononuclear phagocyte system. The results showed no difference in iron uptake across all cell lines, tested doses, and time points. The matching iron uptake profiles of Ferrlecit® and its generic product support the FDA’s present position detailed in the draft guidance on development of SFG complex products that bioequivalence can be based on qualitative (Q1) and quantitative (Q2) formulation sameness, similar physiochemical characterization, and pharmacokinetic bioequivalence studies. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Open AccessArticle Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery
Nanomaterials 2017, 7(12), 435; doi:10.3390/nano7120435
Received: 26 October 2017 / Revised: 23 November 2017 / Accepted: 30 November 2017 / Published: 8 December 2017
Cited by 1 | PDF Full-text (2431 KB) | HTML Full-text | XML Full-text
Abstract
This work investigated the preparation of chitosan nanoparticles used as carriers for doxorubicin for targeted cancer delivery. Prepared nanocarriers were stabilized and functionalized via zinc ions incorporated into the chitosan nanoparticle backbone. We took the advantage of high expression of sarcosine in the
[...] Read more.
This work investigated the preparation of chitosan nanoparticles used as carriers for doxorubicin for targeted cancer delivery. Prepared nanocarriers were stabilized and functionalized via zinc ions incorporated into the chitosan nanoparticle backbone. We took the advantage of high expression of sarcosine in the prostate cancer cells. The prostate cancer targeting was mediated by the AntiSar antibodies decorated surface of the nanocage. Formation of the chitosan nanoparticles was determined using a ninhydrin assay and differential pulse voltammetry. Obtained results showed the strong effect of tripolyphosphine on the nanoparticle formation. The zinc ions affected strong chitosan backbone coiling both in inner and outer chitosan nanoparticle structure. Zinc electrochemical signal depended on the level of the complex formation and the potential shift from −960 to −950 mV. Formed complex is suitable for doxorubicin delivery. It was observed the 20% entrapment efficiency of doxorubicin and strong dependence of drug release after 120 min in the blood environment. The functionality of the designed nanotransporter was proven. The purposed determination showed linear dependence in the concentration range of Anti-sarcosine IgG labeled gold nanoparticles from 0 to 1000 µg/mL and the regression equation was found to be y = 3.8x − 66.7 and R2 = 0.99. Performed ELISA confirmed the ability of Anti-sarcosine IgG labeled chitosan nanoparticles with loaded doxorubicin to bind to the sarcosine molecule. Observed hemolytic activity of the nanotransporter was 40%. Inhibition activity of our proposed nanotransporter was evaluated to be 0% on the experimental model of S. cerevisiae. Anti-sarcosine IgG labeled chitosan nanoparticles, with loaded doxorubicin stabilized by Zn ions, are a perspective type of nanocarrier for targeted drug therapy managed by specific interaction with sarcosine and metallothionein for prostate cancer. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Open AccessArticle Synthesis, Characterization, and Nanomedical Applications of Conjugates between Resorcinarene-Dendrimers and Ibuprofen
Nanomaterials 2017, 7(7), 163; doi:10.3390/nano7070163
Received: 18 May 2017 / Revised: 16 June 2017 / Accepted: 26 June 2017 / Published: 30 June 2017
Cited by 2 | PDF Full-text (2274 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ibuprofen has been reported to possess anticancer activity. In the present work, four ibuprofen conjugates of resorcinarene-Polyamidoamine PAMAM-dendrimers were synthesized with eight or 16 ibuprofen moieties. The ibuprofen was released from the dendrimers in a dependent manner. The drug-conjugated nanoresorcinarene-dendrimers showed higher cellular
[...] Read more.
Ibuprofen has been reported to possess anticancer activity. In the present work, four ibuprofen conjugates of resorcinarene-Polyamidoamine PAMAM-dendrimers were synthesized with eight or 16 ibuprofen moieties. The ibuprofen was released from the dendrimers in a dependent manner. The drug-conjugated nanoresorcinarene-dendrimers showed higher cellular uptake than free ibuprofen. In vitro cytotoxicity studies were performed with free ibuprofen and with the synthesized conjugates in U251, PC-3, K-562, HCT-15, MCF-7, SKLU-1, and MDA U251 (human glioblastoma), PC-3 (human prostatic adenocarcinoma), K-562 (human chronic myelogenous leukemia cells), HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma), SKLU-1 (human lung adenocarcinoma), and MDA-MB-231 (human mammary adenocarcinoma) cancer cell lines by different cytotoxicity assays. Ibuprofen conjugates of the first and second generations showed significant cytotoxic effects towards the human glioblastoma (U251) and human mammary adenocarcinoma (MCF-7, MDA) cell lines. Moreover, the ibuprofen conjugates improved cytotoxicity compared to free ibuprofen. Increased therapeutic efficacy was observed with specific ibuprofen conjugates of the second generation using low doses. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Review

Jump to: Research

Open AccessReview Idebenone: Novel Strategies to Improve Its Systemic and Local Efficacy
Nanomaterials 2018, 8(2), 87; doi:10.3390/nano8020087
Received: 31 December 2017 / Revised: 27 January 2018 / Accepted: 30 January 2018 / Published: 5 February 2018
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Abstract
The key role of antioxidants in treating and preventing many systemic and topical diseases is well recognized. One of the most potent antioxidants available for pharmaceutical and cosmetic use is Idebenone (IDE), a synthetic analogue of Coenzyme Q10. Unfortunately, IDE’s unfavorable
[...] Read more.
The key role of antioxidants in treating and preventing many systemic and topical diseases is well recognized. One of the most potent antioxidants available for pharmaceutical and cosmetic use is Idebenone (IDE), a synthetic analogue of Coenzyme Q10. Unfortunately, IDE’s unfavorable physicochemical properties such as poor water solubility and high lipophilicity impair its bioavailability after oral and topical administration and prevent its parenteral use. In recent decades, many strategies have been proposed to improve IDE effectiveness in the treatment of neurodegenerative diseases and skin disorders. After a brief description of IDE potential therapeutic applications and its pharmacokinetic and pharmacodynamic profile, this review will focus on the different approaches investigated to overcome IDE drawbacks, such as IDE incorporation into different types of delivery systems (liposomes, cyclodextrins, microemulsions, self-micro-emulsifying drug delivery systems, lipid-based nanoparticles, polymeric nanoparticles) and IDE chemical modification. The results of these studies will be illustrated with emphasis on the most innovative strategies and their future perspectives. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Open AccessReview Lipid-Based Nanoparticles as a Potential Delivery Approach in the Treatment of Rheumatoid Arthritis
Nanomaterials 2018, 8(1), 42; doi:10.3390/nano8010042
Received: 24 November 2017 / Revised: 10 January 2018 / Accepted: 12 January 2018 / Published: 15 January 2018
Cited by 2 | PDF Full-text (1416 KB) | HTML Full-text | XML Full-text
Abstract
Rheumatoid arthritis (RA), a chronic and joint-related autoimmune disease, results in immune dysfunction and destruction of joints and cartilages. Small molecules and biological therapies have been applied in a wide variety of inflammatory disorders, but their utility as a therapeutic agent is limited
[...] Read more.
Rheumatoid arthritis (RA), a chronic and joint-related autoimmune disease, results in immune dysfunction and destruction of joints and cartilages. Small molecules and biological therapies have been applied in a wide variety of inflammatory disorders, but their utility as a therapeutic agent is limited by poor absorption, rapid metabolism, and serious side effects. To improve these limitations, nanoparticles, which are capable of encapsulating and protecting drugs from degradation before they reach the target site in vivo, may serve as drug delivery systems. The present research proposes a platform for different lipid nanoparticle approaches for RA therapy, taking advantage of the newly emerging field of lipid nanoparticles to develop a targeted theranostic system for application in the treatment of RA. This review aims to present the recent major application of lipid nanoparticles that provide a biocompatible and biodegradable delivery system to effectively improve RA targeting over free drugs via the presentation of tissue-specific targeting of ligand-controlled drug release by modulating nanoparticle composition. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Open AccessReview Covalent Organic Frameworks: From Materials Design to Biomedical Application
Nanomaterials 2018, 8(1), 15; doi:10.3390/nano8010015
Received: 29 November 2017 / Revised: 21 December 2017 / Accepted: 22 December 2017 / Published: 28 December 2017
Cited by 1 | PDF Full-text (16977 KB) | HTML Full-text | XML Full-text
Abstract
Covalent organic frameworks (COFs) are newly emerged crystalline porous polymers with well-defined skeletons and nanopores mainly consisted of light-weight elements (H, B, C, N and O) linked by dynamic covalent bonds. Compared with conventional materials, COFs possess some unique and attractive features, such
[...] Read more.
Covalent organic frameworks (COFs) are newly emerged crystalline porous polymers with well-defined skeletons and nanopores mainly consisted of light-weight elements (H, B, C, N and O) linked by dynamic covalent bonds. Compared with conventional materials, COFs possess some unique and attractive features, such as large surface area, pre-designable pore geometry, excellent crystallinity, inherent adaptability and high flexibility in structural and functional design, thus exhibiting great potential for various applications. Especially, their large surface area and tunable porosity and π conjugation with unique photoelectric properties will enable COFs to serve as a promising platform for drug delivery, bioimaging, biosensing and theranostic applications. In this review, we trace the evolution of COFs in terms of linkages and highlight the important issues on synthetic method, structural design, morphological control and functionalization. And then we summarize the recent advances of COFs in the biomedical and pharmaceutical sectors and conclude with a discussion of the challenges and opportunities of COFs for biomedical purposes. Although currently still at its infancy stage, COFs as an innovative source have paved a new way to meet future challenges in human healthcare and disease theranostic. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Biocompatible nanostructured materials for cancer diagnostic and therapy
Authors: Tina Mavrič 1,3, Metka Benčina 2, Roghayeh Imani 1, Ita Junkar 2, Damjana Drobne 4, Veronika Kralj-Iglič 3 , Aleš Iglič 1
Affiliations: 1 Laboratory of Biophysics, Faculty of Electrical Engineering, University of Ljubljana, Tržaška 25, SI-1000 Ljubljana, Slovenia
2 Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia
3 Laboratory of Clinical Biophysics, Faculty of Health Sciences, University of Ljubljana, Zdravstvena 5, SI-1000 Ljubljana, Slovenia
4 Bionanoteam, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101,SI-1000 Ljubljana
Abstract: Cancer incidence is on the rise worldwide, according to estimates the cancer related deaths will rise for over 20% in this decade alone. Together with early detection of the disease, a point of care and low invasive treatment method, as opposed to the current severe side effect associated procedures of radio and chemotherapy treatments, is severely needed to act effectively toward the burden of cancer. In the current work we encompass the nanostructures applicable for cancer diagnostics and therapy, the nanodomain approaches being developed on this field to push the frontiers toward clinical trials and overview of the cooperation of nanostructures with oncology-focused pharmaceuticals and the drug-free nanotechnology for cancer treatment. In this regard we will also highlight the resounding achievement of our lab regarding gadolinium-enriched TiO2 microspheres. This material may as well be on the forefront of cancer treatment because it is praised for the biocompatibility, and represents a state of the art possibility of its simultaneous use for cancer diagnosis by using MRI, as well as treatment through ROS production upon UV irradiation.

Title: Drug delivery system for emodin based on mesoporous silica SBA-15
Authors: Tamara Krajnović, Danijela Maksimović-Ivanić, Sanja Mijatović, Dijana Drača, Katharina Wolf, David Edeler, Ludger A. Wessjohann and Goran N. Kaluđerović*
Abstract: In this study mesoporous silica SBA-15 was evaluated as a vehicle for the transport of the cytotoxic natural product emodin (EO). SBA-15 was loaded with different quantities of EO (SBA-15|EO1-SBA-15|EO5: 8-36 %) and characterized by traditional methods. Several parameters (stabilities) and the in vitro behavior on tumor cell lines (melanoma A375, B16 and B16F10) were investigated. SBA-15 suppresses EO release in acidic milieu, pointing out that EO will not be discharged in the stomach. Furthermore, SBA-15 protects EO from photodecomposition. In vitro studies showed a dose dependent decrease of cellular viability which is directly correlated with an increasing amount of EO in SBA-15 for up to 27 % of EO, while a constant activity for 32 % and 36 % of EO in SBA-15 was observed. Additionally, SBA-15 loaded with EO (SBA-15|EO3) does not disturb viability of peritoneal macrophages. SBA-15|EO3 causes inhibition of tumor cell proliferation and triggers apoptosis, connected with caspase activation, upregulation of Bax, as well as Bcl-2 and Bim downregulation along with amplification of PARP fragmentation. Thus, the mesoporous SBA-15 is a promising carrier of the water-insoluble drug emodin.

Title: Lipid-based nanoparticles as a potential drug delivery approach in the treatment of rheumatoid arthritis
Author: Jia-You Fang
Abstract: Rheumatoid arthritis (RA), a chronic and joint-related autoimmune disease, results in immune dysfunction and destruction of joints and cartilages. Small molecules and biologic therapies have been applied in a wide variety of inflammatory disorders, but theirs utility as a therapeutic agent is limited by its poor absorption, rapid metabolism and serious side effects. To improve these limitations, nanoparticles, as drug delivery systems, are capable of encapsulating and protecting drugs from degradation before to reaching target site in vivo. The present researches purpose a platform for different lipid nanoparticles approaches for RA therapy, taking advantage of the new emerging field of lipid nanoparticles to develop a targeted theranostic system for in vivo administration in RA. This review aims at providing that the recent major applications of lipid nanoparticle, a biocompatible and biodegradable delivery system, effectively improve targeting over free drugs via presentation of tissue-specific targeting ligands and offer controlled drug release by altering nanoparticle composition in RA.

Tentative Title: Cabazitaxel loaded electrospinning nanofibers for in situ glioma therapy
Author: Gang Guo
Affiliation: State Key Laboratory of Biotherapy and Cancer Center, Sichuan University
Abstract: Gliomas are the most common tumors in the central nervous system, of which the prognosis is exactly poor. The efficacy of conventional therapeutic methods including surgical removal, radiation therapy and chemotherapy is weakened due to the recurrence of the tumors. Surgical removal is infeasible because of the tumor size and the tumor location, which leads to high mortality of gliomas. On the contrary, the localized drug delivery is a safer and more efficient strategy due to the sustained drug release and reduced drug toxicity. Cabazitaxel (CBZ), a next-generation taxane for the treatment of hormone-refractory prostate cancer, has been proved that can penetrate blood-brain barrier (BBB) and shows potentials for inhibiting tumors in the central nervous system (CNS). In this study, we prepared CBZ loaded nanofibers consisted of PPC and modified chitosan (CS). Chitosan presents bioactivities of antioxidancy, antimicobes and immunocompetence, but its application is hampered by the poor solubility. PDLLA side chains were grafted to chitosan, which broke the intermolecular bonds hence remarkably improved solubility of CS in common organic solvents. The anti-tumor effects of the nanofibers were evaluated ex vivo and in vivo. Annexin V/PI analysis, immunohistochemistry staining (IHC) and TUNEL results confirmed that the CBZ loaded PPC/GTCS mats inhibited the growth of glioma by inhibiting the proliferation and triggering the apoptosis of tumor cells. The CBZ loaded nanofibers showed great potent for the treatment of glioma.

Title: Cationic liposomes carrying siRNA: impact of lipid composition on physicochemical properties, cytotoxicity and endosomal escape
Authors: Anna Lechanteur 1, Vincent Sanna 1, Amandine Duchemin 2, Brigitte Evrard 1, Denis Mottet 2, Géraldine Piel 1
Affiliation:
1 Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, University of Liège, Liège (4000), Belgium
2 Laboratory of Protein Signaling and Interactions, GIGA-Molecular Biology of Diseases, University of Liège, Liège (4000), Belgium
Correspondence: Anna Lechanteur, PhD, ULiege Laboratoire de Technologie Pharmaceutique et Biopharmacie, CHU Bat B36 Tour 4, 1 avenue de l'Hopital, 4000 Liège, Belgium
Phone number: +32 4 366 43 06
Fax: +32 4 366 43 02
E-mail:
Abstract: In recent year, cationic liposomes have gained a lot of attention for siRNA delivery. Despite this, intracellular barriers as endosomal escape and cytosolic delivery of siRNA are still hurdles as well as the cytotoxicity due to cationic lipids. To address these issues, we developed four liposomal formulations composed of two different cationic lipids (DOTAP and DC-Cholesterol) and different ratio of co-lipids (cholesterol and DOPE). The objective is to dissect these impacts on siRNA efficacy and on cytotoxicity. Liposomes were complexed to siRNA at six different N/P molar ratios, physico-chemical properties were characterized and consequently N/P 2.5, 5 and 10 were selected for in vitro experiments. We have shown that the cytotoxicity is influenced by the N/P ratio, the concentration of cationic lipid as well as the nature of the cationic lipid. For instance, cell viability decreased of 70% with liposomes DOTAP/Cholesterol/DOPE 1/0.75/0.5 used at a N/P ratio of 10 whereas the same formulation at a N/P ratio of 2.5 was safe. Interestingly, we have observed difference in terms of mRNA knock-down efficiency whereas the transfection rate was quite similar for each formulation. Liposomes containing 50% of DOPE induced a mRNA extinction of around 80%. This study allowed to highlight crucial parameters in order to develop lipoplexes which are safe and induce an efficient intracytoplasmic release of siRNA.

Title: Development of nano-delivery systems for the delivery and targeting of oncolytic adenoviruses
Abstract: In recent years, oncolytic adenoviruses have been used as anticancer agents and attracting increasing interest in cancer gene therapy due to the selective infection and replication in tumor cells. However, the applications of oncolytic adenovirus are limited by immunogenicity, rapid clearance from blood stream and also reduce adhesion to cell membranes. Cationic polymers and liposomes can efficiently encapsulate the adenovirus by forming the electrostatic force with the surface negative chargers of adenovirus to overcome the limitations and also improve the therapeutic efficacy. In this paper, cationic DOPE/DC-CHOL liposomes and three different cationic polymers: poly (ethylenimine), poly(L-lysine) and DEAE-Dextran were applied as nano-delivery systems for prostate specific oncolytic adenovirus to achieve prostate targeted gene therapy by in vitro and in vivo.

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