Polycaprolactone-<i>b</i>-poly(ethylene Oxide) Block Copolymer Micelles as a Novel Drug Delivery Vehicle for Neurotrophic Agents FK506 and L-685,818

Allen, Christine; Yu, Yingning; Maysinger, Dušica; Eisenberg, Adi

doi:10.1021/bc9702157

Cited by 271 publications

(237 citation statements)

References 28 publications

Supporting

Mentioning

225

Contrasting

Unclassified

Order By: Relevance

“…This high degree of biocompatibility of MePEG-b-PCL diblock copolymers was also reported by other groups in several different cell lines, including erythrocyte, breast cancer, pheochromocytoma, and cervical cancer cells. 3,28,29 The short-term-cytotoxicity study also suggested that the PCL19 and PCL104 copolymers did not cause a high degree of cell lysis, as indicated by low LDH release (Figure 2). Similar to PCL19 and PCL104 copolymers, both short-and long-term cell-viability assays demonstrated that the PCL5 copolymer did not cause cell death at concentrations up to 1% (w/v), suggesting that this copolymer is also highly biocompatible with MDCKII and MDCKII-MDR1 cell lines ( Figure 3A and B).…”

Section: Discussionmentioning

confidence: 90%

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

Wan¹,

Letchford²,

Jackson³

et al. 2013

IJN

View full text Add to dashboard Cite

Two types of nanoparticles were prepared using the diblock copolymer methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-b-PCL), with either a short PCL block length, which forms micelles, or with a longer PCL block length, which forms kinetically "frozen core" structures termed nanospheres. Paclitaxel (PTX)-loaded micelles and nanospheres were evaluated for their cytotoxicity, cellular polymer uptake, and drug accumulation in drug-sensitive (Madin-Darby Canine Kidney [MDCK]II) and multidrug-resistant (MDR) P-glycoprotein (P-gp)-overexpressing (MDCKII-MDR1) cell lines. Both types of PTX-loaded nanoparticles were equally effective at inhibiting proliferation of MDCKII cells, but PTX-loaded micelles were more cytotoxic than nanospheres in MDCKII-MDR1 cells. The intracellular accumulation of both PTX and the diblock copolymers were similar for both nanoparticles, suggesting that the difference in cytotoxicity might be due to the different drug-release profiles. Furthermore, the cytotoxicity of these PTX-loaded nanoparticles was enhanced when these systems were subsequently or concurrently combined with a low-molecular-weight MePEG-b-PCL diblock copolymer, which we have previously demonstrated to be an effective P-gp inhibitor. These results suggest that the dual functionality of MePEG-b-PCL might be useful in delivering drug intracellularly and in modulating P-gp in order to optimize the cytotoxicity of PTX in multidrug-resistant cells.

show abstract

Section: Discussionmentioning

confidence: 90%

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

Wan¹,

Letchford²,

Jackson³

et al. 2013

IJN

View full text Add to dashboard Cite

show abstract

“…Because the peptide contains both hydrophobic and hydrophilic segments, we hypothesized that it could interact with the hydrophobic cargo and still have a good solubility in aqueous solution. Previous work showed that pyrene can be a good hydrophobic model drug because of its low water solubility (Ϸ6 ϫ 10 Ϫ7 M), well-defined fluorescence spectra, and well-established method to statistically analyze the transfer rate of pyrene into liposome vesicles (20)(21)(22)(23)(24)(25). We therefore used this system to measure our peptide-mediated delivery of pyrene into liposomes.…”

Section: Morphological Study By Atomic Force Microscopy (Afm)mentioning

confidence: 99%

Designed amphiphilic peptide forms stable nanoweb, slowly releases encapsulated hydrophobic drug, and accelerates animal hemostasis

Ruan

Zhang

Luo

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

102

View full text Add to dashboard Cite

How do you design a peptide building block to make 2-dimentional nanowebs and 3-dimensional fibrous mats? This question has not been addressed with peptide self-assembling nanomaterials. This article describes a designed 9-residue peptide, N-Pro-Ser-Phe-CysPhe-Lys-Phe-Glu-Pro-C, which creates a strong fishnet-like nanostructure depending on the peptide concentrations and mechanical disruptions. This peptide is intramolecularly amphiphilic because of a single pair of ionic residues, Lys and Glu, at one end and nonionic residues, Phe, Cys, and Phe, at the other end. Circular dichroism and Fourier transform infrared spectroscopy analysis demonstrated that this peptide adopts stable ␤-turn and ␤-sheet structures and self-assembles into hierarchically arranged supramolecular aggregates in a concentration-dependent fashion, demonstrated by atomic force microscopy and electron microscopy. At high concentrations, the peptide dominantly self-assembled into globular aggregates that were extensively connected with each other to form ''beads-on-a-thread'' type nanofibers. These long nanofibers were extensively branched and overlapped to form a self-healing peptide hydrogel consisting of >99% water. This peptide can encapsulate the hydrophobic model drug pyrene and slowly release pyrene from coated microcrystals to liposomes. It can effectively stop animal bleeding within 30 s. We proposed a plausible model to interpret the intramolecular amphiphilic self-assembly process and suggest its importance for the future development of new biomaterials for drug delivery and regenerative medicine.␤-turn/␤-sheet ͉ hemostasis ͉ nanofibers ͉ hydrogel ͉ self-assembly D esign and fabrication of nanoscale biomaterials are critically important for the advancement of biomedical engineering. These include scaffolds for 3D cell and tissue culture, injured tissue repair, and controlled drug release. Biomaterials derived from synthetic or biological polymers have been used extensively for many biomedical applications over decades. Only recently, researchers have attempted to use structural motifs found in nature materials to design and fabricate nanobiomaterials for tissue engineering and regenerative medicine. It is known that many of fibrous proteins and peptides self-assemble into supramolecular structures by using ␤-sheet structures, and one of the typical self-assembling peptides is the RADA16-I (1-9), termed as ionic self-complementary peptide. This kind of peptide has been designed by mimicking native protein motifs containing regular repeats of alternating oppositely charged residues separated by 1 or 2 hydrophobic residues. These residues interact with each other by at least three major forces: interand intramolecular forces such as hydrogen bonding, hydrophobic, and electrostatic interactions to drive molecular selfassembly process. Because charged amino acids play an important role in determining peptide molecular assembly through electrostatic interaction and hydrogen bonding, many of the self-assembling biomaterials are designed to ...

show abstract

“…The hydrophobic blocks form the core of the micelle, which is surrounded by the hydrophilic blocks, which form the outer shell (Zhang and Eisenberg, 1995). The inner core of the micelle creates a hydrophobic microenvironment for the nonpolar drug; while the hydrophilic shell provides a stabilizing interface between the micelle core and the aqueous medium (Allen et al, 1998). The drug delivery systems based on polymeric micelles are generally not stable and drug release is often very fast.…”

Section: Introductionmentioning

confidence: 99%

Design of naltrexone-loaded hydrolyzable crosslinked nanoparticles

Yin

Akala

Taylor

2002

International Journal of Pharmaceutics

View full text Add to dashboard Cite

A hydrolyzable crosslinker (N,O-dimethacryloylhydroxylamine (MANHOMA)) was synthesized by a modified method and was characterized using 1 H-NMR, FTIR, and melting point determination. Naltrexone-loaded nanoparticles were prepared by copolymerization of poly(ethylene glycol)1000 monomethyl ether mono methacrylate (PEO-MA), methyl methacrylate (MMA) and N,O-dimethacryloylhydroxylamine (MANHOMA) in 0.4% poly(vinyl alcohol) aqueous solution. The nanoparticles were characterized by FTIR, particle size determination and transmission electron microscope (TEM). The TEM photomicrographs of the nanoparticles show a crosslinked core surrounded by a ring formed by the polyethylene glycol tail of PEO-MA. The loading efficiency of the nanoparticles and in vitro drug availability from the nanoparticles were investigated. The naltrexone-loaded hydrolyzable crosslinked nanoparticles were able to sustain the release of naltrexone for different periods of time, depending on the monomer feed composition.

show abstract

Polycaprolactone-b-poly(ethylene Oxide) Block Copolymer Micelles as a Novel Drug Delivery Vehicle for Neurotrophic Agents FK506 and L-685,818

Cited by 271 publications

References 28 publications

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

Designed amphiphilic peptide forms stable nanoweb, slowly releases encapsulated hydrophobic drug, and accelerates animal hemostasis

Design of naltrexone-loaded hydrolyzable crosslinked nanoparticles

Contact Info

Product

Resources

About