Mixed micelles formed from graft and diblock copolymers for application in intracellular drug delivery

Lo, Chun Liang; Huang, Chi‐Hsiang; Lin, Ko-Min; Hsiue, Ging‐Ho

doi:10.1016/j.biomaterials.2006.09.050

Cited by 150 publications

(106 citation statements)

References 55 publications

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“…As shown in the TEM image, the dark region of the micellar image was probably attributable to the outer shell formed by the hydrophilic block of BA, whereas the bright region corresponded to the inner core formed by the hydrophobic block of PLGA. 30 All nano-BAs exhibited similar slightly negative surface charges at pH 7.4, whereas the nearly net surface charge of the micelles was able to prevent the recognition of opsonin, thus leading to prolonged in vivo circulation. 31 In addition, from the negative zeta-potential data, we can roughly identify the dominant component on the particle surface.…”

Section: Discussionmentioning

confidence: 99%

Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo

Hong

Gao

Qiu

et al. 2017

IJN

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Bacitracin A (BA) is an excellent polypeptide antibiotic that is active against gram-positive bacteria without triggering multidrug resistance. However, BA is inactive against gram-negative bacteria because of its inability to cross the outer membrane of these cells, and it has strong nephrotoxicity, thus limiting its clinical applications. Nanoantibiotics can effectively localize antibiotics to the periplasmic space of bacteria while decreasing the adverse effects of antibiotics. In this study, biodegradable hydrophobic copolymers of poly ( d , l -lactide-co-glycolide) (PLGA) were attached to the N-termini of BA to design a novel class of self-assembled nano-bacitracin A (nano-BAs), and their potential as antibacterial agents was evaluated in vitro and in vivo. Nano-BAs had a core-shell structure with a mean diameter <150 nm. Impressively, nano-BAs had strong antibacterial properties against both gram-positive and gram-negative bacteria, and the distribution of antibacterial activity as a function of PLGA block length was skewed toward longer PLGA chains. No cytotoxicity against HK-2 cells or human red blood cells (hRBCs) was observed in vitro, suggesting good biocompatibility. A high local density of BA mass on the surface promoted endocytotic cellular uptake, and hydrophobic interactions between the PLGA block and lipopolysaccharide (LPS) facilitated the uptake of nano-BAs, thereby leading to greater antibacterial activities. In addition, Nano-BA 5K was found to be effective in vivo, and it served as an anti-infective agent for wound healing. Collectively, this study provides a cost-effective means of developing self-assembling nano-polypeptide antibiotic candidates with a broader antibacterial spectrum and a lower toxicity than commercially available peptide antibiotics, owing to their modification with biodegradable copolymers.

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Section: Discussionmentioning

confidence: 99%

Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo

Hong

Gao

Qiu

et al. 2017

IJN

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“…Tumor targeting assay and CLSM measurements revealed that multifunctional micelles exhibited a high cytotoxicity by receptor-mediated endocytosis and showed clear fluorescence imaging of their distribution. Although Dox release behavior via intracellular pH changes and the pH and temperature characters of mixed micelles [33] were reported by our previous study, our goal here was to show a proof-of-concept: that is, producing an ideal micelle with a long circulation time, tumor recognition, and combined cancer diagnosis and controlled drug delivery for cancer therapy. In the future, multifunctional micelles combined with a near IR dye (e.g., Cy5.5) to replace FITC can be extended to animal models to evaluate the distribution in the body and cancer therapy.…”

Section: Resultsmentioning

confidence: 99%

Multifunctional Micelles for Cancer Cell Targeting, Distribution Imaging, and Anticancer Drug Delivery

Huang¹,

Lo²,

Chen³

et al. 2007

Adv Funct Materials

148

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Multifunctional micelles for cancer cell targeting, distribution imaging, and anticancer drug delivery were prepared from an environmentally‐sensitive graft copolymer, poly(N‐isopropyl acrylamide‐co‐methacryl acid)‐g‐poly(D,L‐lactide) (P(NIPAAm‐co‐MAAc)‐g‐PLA), a diblock copolymer, methoxy poly(ethylene glycol)‐b‐poly(D,L‐lactide) (mPEG‐PLA) and two functionalized diblock copolymers, galactosamine‐PEG‐PLA (Gal‐PEG‐PLA) and fluorescein isothiocyanate‐PEG‐PLA (FITC‐PEG‐PLA). Anticancer drug, free base doxorubicin (Dox) was incorporated into the inner core of multifunctional micelles by dialysis. From the drug release study, a change in pH (from pH 7.4 to 5.0) deformed the structure of the inner core from that of aggregated P(NIPAAm‐co‐MAAc), causing the release of a significant quantity of doxorubicin (Dox) from multifunctional micelles. Multifunctional micelles target specific tumors by an asialoglycoprotein (HepG2 cells)‐Gal (multifunctional micelle) receptor‐mediated tumor targeting mechanism. This mechanism then causes intracellular pH changes which induce Dox release from multifunctional micelles and that micelles have strong effects on the viability of HepG2 cells and are abolished by galactose. Confocal laser scanning microscopy (CLSM) reveals a clear distribution of multifunctional micelles. With careful design and sophisticated manipulation, polymeric micelles can be widely used in cancer diagnosis, cancer targeting, and cancer therapy simultaneously.

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“…50,51) A solution of BSA (45 mg·mL −1 ) in 0.15 M PBS pH 7.4, which was similar to the concentration found in plasma, was prepared and mixed with CnCA nanoparticles.…”

Section: Preparation Of Ptx-loaded Calixarene Nanoparticlesmentioning

confidence: 99%

Preparation and Characterization of Amphiphilic Calixarene Nanoparticles as Delivery Carriers for Paclitaxel

Zhao

Wang

Han

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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Two types of amphoteric calix[n]arene carboxylic acid (CnCA) derivative, i.e., calix[6]arene hexa-carboxylic acid (C 6 HCA) and calix[8]arene octo-carboxylic acid (C 8 OCA), were synthesized by introducing acetoxyls into the hydroxyls of calix[n]arene (n 6, 8). C 6 HCA and C 8 OCA nanoparticles (NPs) were prepared successfully using the dialysis method. CnCA NPs had regular spherical shapes with an average diameter of 180-220 nm and possessed negative charges of greater than 30 mV. C 6 HCA and C 8 OCA NPs were stable in 4.5% bovine serum albumin solutions and buffers (pH 5-9), with a low critical aggregation concentration value of 5.7 mg·L 1 and 4.0 mg·L 1 , respectively. C 6 HCA and C 8 OCA NPs exhibited good paclitaxel (PTX) loading capacity, with drug loading contents of 7.5% and 8.3%, respectively. The overall in vitro release behavior of PTX from the CnCA NPs was sustained, and C 8 OCA NPs had a slower release rate compared with C 6 HCA NPs. These favorable properties of CnCA NPs make them promising nanocarriers for tumortargeted drug delivery.Key words calix[n]arene carboxylic acid; nanoparticle; paclitaxel; tumor therapy Paclitaxel (PTX) is a well-known anticancer drug that is used primarily to treat lung, breast and ovarian cancers. Similar to most anticancer drugs, its poor solubility in water limits the clinical applications of PTX. Taxol, a widely used clinical formulation of paclitaxel, requires the use of Cremphor-EL as a solubilizer, which has been known to cause serious problems, including hypersensitivity reactions, neurotoxicity, and nephrotoxicity.1,2) Moreover, the lack of selectivity of PTX results in significant toxicity to noncancerous cells and severely impacts patients' quality of life. Therefore, there is a dire need for the development of a novel formulation that improves the solubility of PTX and decreases its side effects.Among various alternatives, nano-sized drug delivery system (nano-DDS) is one of the best choices. Nano-DDS not only greatly enhances the solubility of PTX without side effects, but it also promotes intra-tumoral drug accumulation through the enhanced permeability and retention (EPR) effect.3,4) Many nano-DDSs of PTX have been reported, and some of them have been marketed. Abraxane, a nanosuspension of paclitaxel encapsulated in human albumin was approved by the Food and Drug Administration (FDA) in 2005 for the treatment of metastatic breast cancer.5) A liposomebased PTX formulation, Lipusu, has been applied for the treatment of ovarian cancer in China.6) In addition to these approved drugs, a number of PTX nano-DDSs, such as polymeric nanoparticles (NPs), 7-9) inorganic NPs, 10) nano-emulsions, 11) carbon nanotubes, 12) and nanogels, 13) have been reported in preclinical studies. Although these novel PTX nano-DDSs exhibit varying levels of success, methods for improving the safety, stability and specificity of nano-DDS still warrant further research.Calixarenes have been used as an important class of macrocyclic host molecules in supramolecular chemistry.14) Becaus...

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Mixed micelles formed from graft and diblock copolymers for application in intracellular drug delivery

Cited by 150 publications

References 55 publications

Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo

Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo

Multifunctional Micelles for Cancer Cell Targeting, Distribution Imaging, and Anticancer Drug Delivery

Preparation and Characterization of Amphiphilic Calixarene Nanoparticles as Delivery Carriers for Paclitaxel

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