Monthly Archives: May 2013

“Nanoparticle Network Acts As An Artificial Pancreas”

By Melissae Fellet

“Researchers are working on creating implantable or injectable synthetic materials that release insulin in response to glucose levels, mimicking the natural action of the pancreas. A new material made from nanoparticles could improve how quickly these synthetic pancreases respond to glucose levels (ACS Nano 2013, DOI: 10.1021/nn400630x). Materials with fast response times would improve the health and quality of life for people living with diabetes, the researchers say.”

 

To see the rest of this article please refer to Chemical and Engineering Newsletter May 20, 2013, Volume 91, Issue 20

“Hydrogel Implants Slip Past Immune Defenses”

Biomaterials: Coating could prevent implant rejection

By Celia Henry Arnaud

“The human body almost immediately recognizes surgically implanted objects as foreign and rushes to surround them with a dense layer of collagen. That so-called foreign-body response is part of an immune-system reaction to a strange object. However, it interferes with medical implants such as drug pumps.

Coating implants with some novel hydrogels may help. The hydrogels are zwitterionic—carrying both positive and negative charges—and are based on carboxybetaine. When Shaoyi Jiang, Buddy D. Ratner, and coworkers at the University of Washington, Seattle, put these hydrogels in mice, the implants resisted the foreign-body reaction for at least three months (Nat. Biotechnol. 2013, DOI: 10.1038/nbt.2580).”

To see the rest of the article please refer to Chemical and Engineering News, Volume 91 Issue 20 | p. 9 | News of The Week
Issue Date: May 20, 2013 | Web Date: May 17, 2013

 

New technique can help nanoparticles deliver drug treatments

A Wayne State University researcher has successfully tested a technique that can lead to more effective use of nanoparticles as a drug delivery system.

Joshua Reineke, Ph.D., assistant professor of pharmaceutical sciences in the Eugene Applebaum College of Pharmacy and Health Sciences, examined how a polylactic-co-glycolic acid (PLGA) breaks down in live tissue

More here from phys.org, taken from the journal Molecular Pharmaceutics and a link to the article.

Surface Analysis of PEGylated Nano-Shields on Nanoparticles Installed by Hydrophobic Anchors

Ebbeson et al. showed use of PolyVivo AK10 as a component for making PEG shielded nanoparticles.

Abstract: Purpose This work describes a method for functionalisation of nanoparticle surfaces with hydrophilic “nano-shields” and the application of advanced surface characterisation to determine PEG amount and accumulation at the outmost 10 nm surface that is the predominant factor in determining protein and cellular interactions.

Methods: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared with a hydrophilic PEGylated “nano-shield” inserted at different levels by hydrophobic anchoring using either a phospholipid-PEG conjugate or the copolymer PLGA-block-PEG by an emulsification/diffusion method. Surface and bulk analysis was performed including X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance spectroscopy (NMR) and zeta potential. Cellular uptake was investigated in RAW 264.7 macrophages by flow cytometry.

Results: Sub-micron nanoparticles were formed and the combination of (NMR) and XPS revealed increasing PEG levels at the particle surface at higher PLGA-b-PEG copolymer levels. Reduced cellular interaction with RAW 264.7 cells was demonstrated that correlated with greater surface presentation of PEG.

This work demonstrates a versatile procedure for decorating nanoparticle surfaces with hydrophilic “nano-shields”. XPS in combination with NMR enabled precise determination of PEG at the outmost surface to predict and optimize the biological performance of nanoparticle-based drug delivery.

— Ebbesen, M. F., et al. Pharmaceutical research (2013): 1-10.(http://link.springer.com/article/10.1007/s11095-013-1018-3)

Polydopamine-Based Surface Modification for the Development of Peritumorally Activatable Nanoparticles

Gulloti et. al. used PEG-PLGA from PolyScitech (AK30, mPEG-PLGA 5000-4000 Da).

Abstract: Purpose: To create poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), where a drug-encapsulating NP core is covered with polyethylene glycol (PEG) in a normal condition but exposes a cell-interactive TAT-modified surface in an environment rich in matrix metalloproteinases (MMPs).

Methods: PLGA NPs were modified with TAT peptide (PLGA-pDA-TAT NPs) or dual-modified with TAT peptide and a conjugate of PEG and MMP-substrate peptide (peritumorally activatable NPs, PANPs) via dopamine polymerization. Cellular uptake of fluorescently labeled NPs was observed with or without a pre-treatment of MMP-2 by confocal microscopy and flow cytometry. NPs loaded with paclitaxel (PTX) were tested against SKOV-3 ovarian cancer cells to evaluate the contribution of surface modification to cellular delivery of PTX.

Results: While the size and morphology did not significantly change due to the modification, NPs modified with dopamine polymerization were recognized by their dark color. TAT-containing NPs (PLGA-pDA-TAT NPs and PANPs) showed changes in surface charge, indicative of effective conjugation of TAT peptide on the surface. PLGA-pDA-TAT NPs and MMP-2-pre-treated PANPs showed relatively good cellular uptake compared to PLGA NPs, MMP-2-non-treated PANPs, and NPs with non-cleavable PEG. After 3 h treatment with cells, PTX loaded in cell-interactive NPs showed greater toxicity than non-interactive ones as the former could enter cells during the incubation period. However, due to the initial burst drug release, the difference was not as clear as microscopic observation.

Conclusions: PEGylated polymeric NPs that could expose cell-interactive surface in response to MMP-2 were successfully created by dual modification of PLGA NPs using dopamine polymerization.

—  E Gullotti, J Park, Y Yeo – Pharmaceutical research, 2013 – Springer.   http://link.springer.com/article/10.1007/s11095-013-1039-y