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. 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
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

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

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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 (9 papers)

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Research

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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 1 | 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
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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
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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

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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
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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
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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: 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.

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