Search

A facile strategy for the fabrication of multi-functional polymer/inorganic hybrid nanoparticles for efficient gene and drug co-delivery was developed. A therapeutic gene (p53 plasmid) and a chemotherapy drug (doxorubicin hydrochloride, DOX) were co-loaded simultaneously in hybrid nanoparticles during co-precipitation with high encapsulation efficiency. The prepared heparin-biotin/heparin/ CaCO3/calcium phosphate/ DNA/ DOX ( HPB/ HP/ CaCO3/ CaP/ DNA/ DOX) nanoparticles exhibited pH sensitivity and tumor-targeting property due to the presence of the CaCO3/ CaP inorganic component and biotin moiety in the polymer chain, respectively. For comparison, HPB/ HP/ CaCO3/ CaP/ DOX hybrid nanoparticles for drug delivery were also fabricated. The cell inhibition effects of different nanoparticles on HeLa cells were evaluated using methylthiazole tetrazolium assay. In vitro study indicated that the gene and drug co-delivery system ( HPB/ HP/ CaCO3/ CaP/ DNA/ DOX) showed a stronger cell growth inhibition effect as compared with the drug delivery system ( HPB/ HP/ CaCO3/ CaP/ DOX), indicating that HPB/ HP/ CaCO3/ CaP/ DNA/ DOX hybrid nanoparticles could effectively mediate gene transfection and deliver the drug. The hybrid nanoparticles with good biocompatibility have great promise for gene and drug co-delivery. © 2014 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Amphiphilic copolymers are well developed as precursors for the preparation of micellar drug carriers. Poly(N-isopropylacrylamide) (PNIPAAm) is one of the most extensively studied thermo-sensitive polymers that exhibits a lower critical solution temperature (LCST) at around 33°C in aqueous solution. Over the past decade, considerable efforts have been devoted to design and preparation of PNIPAAm-based thermo-sensitive polymeric micelles as delivery vehicles for controlled drug release. Present review highlights the recent developments in this field, and focuses on two categories of PNIPAAm-based copolymer micelles as smart drug delivery systems, i.e. micelles with PNIPAAm as hydrophilic shell-forming segments below the LCST and micelles with PNIPAAm as hydrophobic core-forming segments above the LCST. [Copyright &y& Elsevier]

Abstract: Hyperbranched amphiphilic polymer PG6–PLA–PEG was synthesized through grafting hydrophobic poly(d,l-lactide) (PLA) segments and hydrophilic poly(ethylene glycol) (PEG) blocks to hydrophilic hyperbranched polyglycerol core (PG6), subsequently. To achieve cell targeting property, folic acid (FA) was further incorporated to the hyperbranched polymer to obtain PG6–PLA–PEG–FA. The polymers were characterized by 1H NMR, UV–vis spectroscopy and combined size-exclusion chromatography and multiangle laser light scattering (SEC-MALLS) analysis. Due to the amphiphilicity, PG6–PLA–PEG and PG6–PLA–PEG–FA could self-assemble to form nanoparticles in aqueous solutions. Antineoplastic drug, paclitaxel (PTX), was encapsulated into the nanoparticles. The nanoparticles were observed by transmission electron microscopy (TEM). The targeting property of PG6–PLA–PEG–FA was evaluated in vitro. The results showed that the PTX loaded PG6–PLA–PEG–FA nanoparticles exhibited enhanced inhibition on folate receptor positive tumor cells due to the folate mediated targeting. [Copyright &y& Elsevier]

Graphical abstract Aptamer-functionalized albumin-based nanoparticles can effectively deliver the drug to targeted tumor cells to achieve enhanced therapeutic efficiency. Highlights • A tumor targeting aptamer-functionalized albumin-based drug delivery system was prepared. • A hydrophobic drug was employed to trigger the self-assembly of bovine serum albumin. • Aptamer-functionalized nanoparticles show enhanced tumor cell inhibitory efficacy. • Aptamer-functionalized nanoparticles can induce cell apoptosis more effectively. • Aptamer-functionalized nanoparticles can prevent tumor progression more effciently. Abstract Proteins have been extensively explored as versatile nanocarriers for drug delivery due to their complete biocompatibility, ease of surface modification, and lack of toxicity and immunogenicity. In this study, a facile strategy was used to construct aptamer-functionalized albumin-based nanoparticles for effective drug delivery and targeted cancer therapy. A hydrophobic drug, doxorubicin (DOX) was employed to trigger the self-assembly of bovine serum albumin (BSA) to from stable nanoparticles via hydrophobic interaction, and then a tumor targeting aptamer AS1411 was incorporated to the surface of DOX loaded BSA. Due to the specific recognition between AS1411 and its receptor over-expressed on tumor cells, the aptamer-modified nanoparticles show higher cellular uptake and stronger cell inhibitory efficacy against cancerous MCF-7 cells as compared with the nanoparticles without aptamer modification. In addition, DOX loaded aptamer-functionalized nanoparticles can induce more significant down-regulation of Bcl-2 and PCNA as well as up-regulation of pRB, PARP and Bax in MCF-7 cells compared with unmodified nanoparticles, indicating the aptamer modification can induce cell apoptosis more effectively. Besides, aptamer-modified nanoparticles exhibit a significantly improved capability in up-regulating p16, p21 and E-cadherin, and down-regulating EpCAM, vimentin, Snail, MMP-9, CD44 and CD133, implying the favorable effects of drug delivery on the prevention of tumor progression and metastasis. [ABSTRACT FROM AUTHOR]

A facile strategy to prepare nano-sized drug carriers for co-delivery of multiple types of drugs in combination chemotherapy was developed. Inorganic/organic hybrid alginate/CaCO 3 nanoparticles were prepared by co-precipitation in an aqueous solution under very mild conditions. A hydrophilic drug (doxorubicin hydrochloride, DOX) and a hydrophobic drug (paclitaxel, PTX) were co-encapsulated in the hybrid nanoparticles. For comparison, PTX loaded nanoparticles and DOX loaded nanoparticles were also prepared. The measurement based on dynamic light scattering indicated all nanoparticles had a mean size less than 200 nm with a relatively narrow size distribution. The morphology of the nanoparticles was observed by TEM. The in vitro drug release study showed that the release of DOX and PTX from the dual drug loaded nanoparticles could be effectively sustained. The tumor cell inhibitory effect of the drug loaded nanoparticles was evaluated in HeLa cells and MCF-7/ADR cells. The dual drug loaded nanoparticles exhibited significantly enhanced cell uptake and nuclear localization as compared with the single drug loaded nanoparticles. As a result, the dual drug loaded nanoparticles had a significantly enhanced cell inhibitory effect, especially for drug resistant tumor cells. These results indicated that alginate/CaCO 3 hybrid nanoparticles have promising applications for the co-delivery of drugs with different physicochemical properties in combination chemotherapy to overcome multidrug resistance. [ABSTRACT FROM AUTHOR]

Abstract: In this study, a facile strategy to effectively improve the delivery efficiency of nano-sized drug delivery systems was developed. Calcium phosphate/carboxymethyl chitosan (Ca–P/CMC) hybrid nanoparticles were prepared by the precipitation of calcium phosphate in the aqueous solution containing CMC. The obtained Ca–P/CMC nanoparticles were characterized by SEM, XPS and TGA. Doxorubicin hydrochloride (DOX), a water-soluble anticancer drug, was loaded in the nanoparticles with high encapsulation efficiency. The in vitro drug release showed that the release of DOX from the nanoparticles could be effectively sustained. After drug loading, the nanoparticles were decorated by peptide KALA by self-assembly through the electrostatic interaction between the positively charged KALA and the negatively charged CMC chains to obtain drug loaded Ca–P/CMC/KALA nanoparticles. The size and size distribution of the nanoparticles were measured by a particle size analyzer. The KALA decorated nanoparticles exhibited a larger size and an increased zeta potential. The effect of KALA content on the HeLa cell inhibition was studied. The in vitro study showed that the cell inhibition effect could be significantly enhanced by the presence of KALA. [Copyright &y& Elsevier]

Abstract: A facile method to prepare inorganic/organic hybrid heparin/CaCO3/CaP nanoparticles for drug delivery was developed. The heparin/CaCO3/CaP nanoparticles were prepared by the co-precipitation of Ca2+ ions with carbonate and phosphate ions in the presence of heparin. The effects of ion concentrations on the particle size and properties of the nanoparticles were investigated. The dynamic light scattering (DLS) particle size analysis and scanning electron microscopy (SEM) observation showed that the mean size of the hybrid nanoparticles could be controlled at less than 50nm in the dried state through adjusting the concentrations of the inorganic ions. Fourier transform infrared (FTIR) spectroscopy indicated that the crystallization of CaCO3 could be suppressed with the presence of phosphate ions in the co-precipitation system. X-ray photoelectron spectroscopy (XPS) showed that the heparin content in the surface layer of heparin/CaCO3/CaP hybrid nanoparticles decreased with the increasing ion concentrations during the nanoparticle preparation. The drug loading and release properties of the hybrid nanoparticles with different sizes and different compositions were studied. The in vitro cellular cytotoxicity indicated that blank hybrid nanoparticles had good biocompatibility, whereas doxorubicin hydrochloride (DOX) loaded nanoparticles exhibited a strong cell inhibition effect, indicating that the heparin/CaCO3/CaP hybrid nanoparticles could be promising carriers for drug delivery. [Copyright &y& Elsevier]

Abstract: Alginate based microparticle drug delivery systems were prepared for the sustained release of antineoplastic drugs. Two drugs, 5-fluorouracil (5-FU) and tegafur, were encapsulated into the microparticles. The drug loaded microparticles were fabricated using a very convenient method under very mild conditions, i.e., directly shredding the drug loaded beads into microparticles in a commercial food processor. The mean sizes of the obtained microparticles were between 100 and 200μm. To effectively sustain the drug release, alginate microparticles were reinforced by chitosan during gelation. The drug release from the chitosan-reinforced alginate microparticles was obviously slower than that from the unreinforced microparticles. The effect of the reinforcement conditions on the drug release property of the microparticles was studied, and the optimized concentration of chitosan solution for reinforcement was identified. The effects of drug feeding concentration and pH value of the release medium on the drug release were investigated. [Copyright &y& Elsevier]