ABSTRACT
We developed a novel linear pH-sensitive conjugate methoxy poly(ethylene glycol)-4ß-aminopodophyllotoxin (mPEG-NPOD-I) by a covalently linked 4ß-aminopodophyllotoxin (NPOD) and PEG via imine bond, which was amphiphilic and self-assembled to micelles in an aqueous solution. The mPEG-NPOD-I micelles simultaneously served as an anticancer drug conjugate and as drug carriers. As a drug conjugate, mPEG-NPOD-I showed a significantly faster NPOD release at a mildly acidic pH of 5.0 and 4.0 than a physiological pH of 7.4. Notably, it was confirmed that this drug conjugate could efficiently deliver NPOD to the nuclei of the tumor cells and led to much more cytotoxic effects to A549, Hela, and HepG2 cancer cells than the parent NPOD. The half maximal inhibitory concentration (IC50) of mPEG-NPOD-I was about one order magnitude lower than that of the NPOD. In vivo, mPEG-NPOD-I reduced the size of the tumors significantly, and the biodistribution studies indicated that this drug conjugate could selectively accumulate in tumor tissues. As drug carriers, the mPEG-NPOD-I micelles encapsulated hydrophobic PTX with drug-loading efficiencies of 57% and drug-loading content of 16%. The loaded PTX also showed pH-triggered fast release behavior, and good additive cytotoxicity effect was observed for the PEG-NPOD-I/PTX. We are convinced that these multifunctional drug conjugate micelles have tremendous potential for targeted cancer therapy.
Subject(s)
Antineoplastic Agents/chemistry , Drug Delivery Systems/methods , Micelles , Polymers/chemistry , Animals , Antineoplastic Agents/pharmacokinetics , Cell Line, Tumor , Dose-Response Relationship, Drug , Humans , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Male , Mice , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Tissue DistributionABSTRACT
Photoreversible micelles were achieved by a combination of commercially available components sodium alginate (Alg), tetradecyltrimethylammonium bromide (TTAB), α-cyclodextrin (α-CD), and 4-(phenylazo)benzoic acid (PBA). Under visible light irradiation, α-CD interacted more favorably with PBA than with alkyl chains of TTAB. Therefore, polymer-surfactant micelles were formed by the self-assembly of Alg and TTAB through electrostatic attraction. After UV irradiation, micelles were disrupted because PBA in the cis form lost its ability to complex with α-CD, and then the latter was interacted with TTAB to prevent the association of alkyl chains of TTAB. On alternating irradiation of this quaternary system with UV and visible light, this reversible micellization process can be recycled many times.
Subject(s)
Micelles , Polymers/chemistry , Surface-Active Agents/chemistry , alpha-Cyclodextrins/chemistry , Benzoic Acid/chemistry , Models, Theoretical , Trimethyl Ammonium Compounds/chemistry , Ultraviolet RaysABSTRACT
A kind of novel magnetic hollow spheres was prepared by encapsulating magnetofluid into polymeric hollow spheres. Polymeric hollow nanospheres were constructed by self-assembly of rod-coil complexes, in which the rod-like segments were formed by inclusion of α-cyclodextrins (α-CD) and grafting poly(ethylene glycol) (PEG) chains of chitosan-graft-PEG (CS-g-PEG). Structural characteristics of CS-g-PEG/α-CD hollow spheres were investigated in detail by NMR, XRD, TEM, etc. Furthermore, those hollow spheres showed a pH responsive property which induced a considerable change of their radius. Magnetofluid was physically entrapped into the empty domain while hollow spheres were formed, it was found that the hollow spheres can encapsulate large quantities of magnetofluid and the encapsulated magnetofluid still possess magnetic responsiveness properties. We expect that this strategy may be served as a novel and more straightforward approach to obtain magnetic hollow spheres for biomedical application.
Subject(s)
Chitosan , Nanospheres/chemistry , Polymers , alpha-Cyclodextrins , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Chitosan/chemical synthesis , Chitosan/chemistry , Magnetic Resonance Spectroscopy , Magnetics , Polyethylene Glycols/chemical synthesis , Polyethylene Glycols/chemistry , Polymers/chemical synthesis , Polymers/chemistry , alpha-Cyclodextrins/chemical synthesis , alpha-Cyclodextrins/chemistryABSTRACT
A novel pH sensitive shape-memory polymer (SMP) is prepared by cross-linking the ß-cyclodextrin modified alginate (ß-CD-Alg) and diethylenetriamine modified alginate (DETA-Alg): The pH reversible ß-CD-DETA inclusion complexes serve as a reversible phase, and the cross-linked alginate chains serve as a fixing phase. It is shown that this material can be processed into temporary shape as we needs at pH 11.5 and recover to its initial shape at pH 7. The recovery ratio and the fixity ratio were 95.7 ± 0.9% and 94.8 ± 1.1%, respectively. Furthermore, this material showed good degradability and biocompatibility. Because the shape transition pH value is quite close to that of our body fluid and this pH triggered shape-memory effect is convenient and safe to use, this material has a high potential for medical application.
Subject(s)
Alginates/chemistry , Biocompatible Materials/chemistry , Polymers/chemistry , Cross-Linking Reagents/chemistry , Hydrogen-Ion Concentration , Temperature , beta-Cyclodextrins/chemistrySubject(s)
DNA/metabolism , Nanospheres , Polymers/chemistry , Transfection/methods , beta-Cyclodextrins/chemistry , Cell Survival/drug effects , DNA/chemistry , Dose-Response Relationship, Drug , Galactosidases/genetics , Galactosidases/metabolism , Hep G2 Cells , Humans , Lac Operon , Microscopy, Electron, Transmission , Molecular Structure , Nucleic Acid Conformation , Particle Size , Polyethylene Glycols/chemistry , Polyethyleneimine/chemistry , Polyethylenes/chemistry , Polymers/toxicity , Polypropylenes/chemistry , Propylene Glycols/chemistry , beta-Cyclodextrins/toxicitySubject(s)
Chitosan/chemical synthesis , Gene Transfer Techniques , Polyethylene Glycols/chemical synthesis , alpha-Cyclodextrins/chemical synthesis , Chitosan/analogs & derivatives , DNA/chemistry , DNA/metabolism , Light , Magnetic Resonance Spectroscopy , Microscopy, Electron, Transmission , Molecular Conformation , Particle Size , Porosity , Scattering, Radiation , Solubility , Water/chemistryABSTRACT
This paper studies a kind of hollow nanospheres prepared by self-assembly ß-cyclodextrins (ß-CDs) and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (pluronic F127) for gene delivery. It was found that this kind of hollow nanospheres enable load PEI10K/DNA and the resulting F127NH2 ßCD/(PEI10K/DNA) with 0.08 µg/well DNA display equal or higher gene delivery capability compared to PEI10K/DNA with 1 µg/well DNA in the absence or presence of serum. The cytotoxicity of the nanospheres was over 100 times lower than that of PEI10K.
Subject(s)
Gene Transfer Techniques , Nanospheres/chemistry , Poloxamer/chemistry , beta-Cyclodextrins/chemistry , Hep G2 Cells , HumansABSTRACT
Degradable hollow nanospheres are prepared by self-assembly of rod-coil Alg-g-PEG/alpha-CD (Alginate-g-Poly(ethylene glycol)/alpha-Cyclodextrin) complexes in water, in which the rod-like segments were formed by inclusion between alpha-CDs and grafted PEG chains and the coil-like segments were protonated alginate backbones.
Subject(s)
Alginates/chemistry , Biocompatible Materials/chemistry , Nanospheres/chemistry , Polyethylene Glycols/chemistry , alpha-Cyclodextrins/chemistry , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Nanospheres/ultrastructure , Water/chemistryABSTRACT
A novel supramolecular network has been prepared based on the formation of inclusion complexes between γ-cyclodextrin and poly(ethylene glycol), in which the PEG chains are interlocked by γ-CD rings. This PEG/γ-CD network exhibits good shape memory behavior because of the crosslinked structure. The crosslinked PEG/γ-CD inclusion complexes and PEG crystallites account for the fixing phase and reversible phase, respectively. The characteristics of the materials have been investigated by (1) H NMR spectroscopy, XRD, DSC, DMA, viscosity tests, and swelling measurements.
