ABSTRACT
The therapeutic outcome of chemotherapy is severely limited by intrinsic or acquired drug resistance, the most common causes of chemotherapy failure. In the past few decades, advancements in nanotechnology have provided alternative strategies for combating tumor drug resistance. Drug-loaded nanoparticles (NPs) have several advantages over the free drug forms, including reduced cytotoxicity, prolonged circulation in the blood and increased accumulation in tumors. Currently, however, nanoparticulate drugs have only marginally improved the overall survival rate in clinical trials because of the various pathophysiological barriers that exist in the tumor microenvironment, such as intratumoral distribution, penetration and intracellular trafficking, etc. Smart NPs with stimulus-adaptable physico-chemical properties have been extensively developed to improve the therapeutic efficacy of nanomedicine. In this review, we summarize the recent advances of employing smart NPs to treat the drug-resistant tumors by overcoming the pathophysiological barriers in the tumor microenvironment.
Subject(s)
Drug Resistance, Neoplasm/drug effects , Nanoparticles/therapeutic use , Tumor Microenvironment/drug effects , Drug Delivery Systems , Humans , Models, BiologicalABSTRACT
Poly(octadecanoic anhydride) (POA) has been prepared by melt polycondensation of octadecanoic diacid. POA was characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD). The results of in vitro degradation and SEM micrographs show that the erosion process of POA is neither bulk nor perfect surface erosion but rather has elements of both in phosphate buffer at 37 degrees C. The moving erosion front is characteristic of surface erosion whereas the remaining porous shell stems from bulk erosion. While a significant special degradation property of POA is that POA presents a very slow degradation rate in acidic condition (pH 5.98), only 1.64% weight loss for 20 days, and it completely degrades after 18 days in basic buffer (pH 7.4). Comparing with poly(sebacic anhydride) (PSA), POA has the higher crystallization degree, and the slower hydrolytic rate.
Subject(s)
Anhydrides/chemistry , Biocompatible Materials/chemistry , Polymers/chemistry , Stearic Acids/chemistry , Biodegradation, Environmental , Buffers , Calorimetry, Differential Scanning , Crystallization , Hydrogen-Ion Concentration , Hydrolysis , In Vitro Techniques , Materials Testing , Microscopy, Electron, Scanning , Spectroscopy, Fourier Transform Infrared , Temperature , X-Ray DiffractionABSTRACT
O-carboxymethyl chitosan/methoxy poly(ethylene glycol) graft copolymers (OCMCS-g-MPEGs) with different degrees of substitution (DS) were synthesized by reductive N-alkylation of chitosan with poly(ethylene glycol) aldehyde. The properties of OCMCS-g-MPEGs, including the solubility, structure, hydrodynamic behaviors, isoelectric point (IEP) and interaction with water-soluble chitosan, were investigated. As a PEGylated polyampholyte, OCMCS-g-MPEGs can resolve in water over all pH range and the pH value at IEP (pH(IEP)) decreases when DS increases. The hydrodynamic behaviors of OCMCS-g-MPEGs in deionized H(2)O are markedly affected by DS and pH(IEP) in the experiment concentration range. The particle size of the complexes of OCMCS-g-MPEGs with water-soluble chitosan is strongly affected by the concentration of water-soluble chitosan and the pH value.
Subject(s)
Chitosan/analogs & derivatives , Polyethylene Glycols/chemistry , Polymers/chemical synthesis , Biocompatible Materials/chemical synthesis , Chitosan/chemistry , Hydrogen-Ion Concentration , Materials Testing , Molecular StructureABSTRACT
AIM: To investigate the paclitaxel-loaded nanoparticles of poly(ethylene glycol)-b-poly(D,L-lactic acid) amphiphilic diblock copolymer (PMT). METHODS: PMT was prepared by solid dispersion technique. The average size and size distribution were determined by dynamic light scattering (DLS). The morphology was characterized by transmission electron microscopy (TEM) and 1HNMR. The influences of the copolymer molecular weight and the paclitaxel-fed amount on PMT were studied. Therapeutic effect of PMT was studied on Kunming mice liver cancer H22. RESULTS: PMT showed nanometer size and spherical morphology with core and shell. The sizes of PMT increased with increasing the molecular weight of the hydrophobic segment in PEDLLA or increasing the drug-loaded amount. The tumour inhibiting effect of PMT was similar with that of Taxol. CONCLUSION: It will provide an experiment basis for the development of new kind of intravenous administration of paclitaxel.
Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Paclitaxel/administration & dosage , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Delayed-Action Preparations , Drug Carriers , Drug Delivery Systems , Lactic Acid , Liver Neoplasms, Experimental/pathology , Mice , Microspheres , Nanotechnology , Paclitaxel/pharmacology , Particle Size , Polyethylene GlycolsABSTRACT
Nanoparticles had received much attention in the development of new kind of pharmaceutical formation because of the special nano-effectivity. Recently, some studies discovered the special functions of the nanoparticles in transdermal and transmucosal drug delivery systems. Even though the acting mechanism of the nanoparticles in these drug delivery systems are not known, these discoveries of the special function of the nanoparticles provide new developing prospect to the drug delivery systems. This paper mainly reviews the present studying results about the nanoparticles used in the transdermal and transmucosal drug delivery systems, including the lipid nanopaticles, natural polymer and the synthesized polymer nanoparticles.