The preliminary evaluation on cholesterol-modified pullulan as a drug nanocarrier

Shen, Shigang; Li, Haiying; Yang, Wenzhi

doi:10.3109/10717544.2014.895068

Cited by 38 publications

(12 citation statements)

References 35 publications

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“…Then, 2 mL of the solution of release media was collected and substituted with an equal volume of the fresh solution at pre-defined time intervals (Ti). The drug release amount was measured by UV spectrometer (UV-384 plus, Molecular Devices, Thermo Fisher Scientific Inc., Waltham, MA, USA), and The percentage rate of drug release ( Q %) was measured as follows [30].

Q % = false(C_{n} \times V + V_{n} true \sum_{i = 0}^{i = n} C_{i} false) / W_{d r u g - l o a d i n g}

where C n is the sample concentration at T n , V is the total volume of release medium, V i is the sample volume at T i , C i is the sample concentration at T i (both V 0 and C 0 were equal to zero), and T n is the sampling at the N th time.…”

Section: Methodsmentioning

confidence: 99%

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Cholesterol-Modified Amino-Pullulan Nanoparticles as a Drug Carrier: Comparative Study of Cholesterol-Modified Carboxyethyl Pullulan and Pullulan Nanoparticles

et al. 2016

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To search for nano-drug preparations with high efficiency in tumor treatment, we evaluated the drug-loading capacity and cell-uptake toxicity of three kinds of nanoparticles (NPs). Pullulan was grafted with ethylenediamine and hydrophobic groups to form hydrophobic cholesterol-modified amino-pullulan (CHAP) conjugates. Fourier transform infrared spectroscopy and nuclear magnetic resonance were used to identify the CHAP structure and calculate the degree of substitution of the cholesterol group. We compared three types of NPs with close cholesterol hydrophobic properties: CHAP, cholesterol-modified pullulan (CHP), and cholesterol-modified carboxylethylpullulan (CHCP), with the degree of substitution of cholesterol of 2.92%, 3.11%, and 3.46%, respectively. As compared with the two other NPs, CHAP NPs were larger, 263.9 nm, and had a positive surface charge of 7.22 mV by dynamic light-scattering measurement. CHAP NPs showed low drug-loading capacity, 12.3%, and encapsulation efficiency of 70.8%, which depended on NP hydrophobicity and was affected by surface charge. The drug release amounts of all NPs increased in the acid media, with CHAP NPs showing drug-release sensitivity with acid change. Cytotoxicity of HeLa cells was highest with mitoxantrone-loaded CHAP NPs on MTT assay. CHAP NPs may have potential as a high-efficiency drug carrier for tumor treatment.

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Q % = false(C_{n} \times V + V_{n} true \sum_{i = 0}^{i = n} C_{i} false) / W_{d r u g - l o a d i n g}

Section: Methodsmentioning

confidence: 99%

“…Because pullulan has a large amount of hydroxyl groups, it can graft small molecules such as cholesterol for hydrophobic modification and forming amphiphilic polymers [29]. As a drug carrier, cholesterol-modified pullulan (CHP) NPs can improve therapeutic efficiency because of high drug-loading and tumor-targeting [30]. …”

Section: Introductionmentioning

confidence: 99%

Cholesterol-Modified Amino-Pullulan Nanoparticles as a Drug Carrier: Comparative Study of Cholesterol-Modified Carboxyethyl Pullulan and Pullulan Nanoparticles

et al. 2016

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“…CHP nanoparticles as a drug carrier had been studied for a long time, which had showed excellent nanomaterials for drug delivery [ 28 , 29 ]. In a previous experiment, we studied the interaction between HSA and pullulan NPs with different degrees of cholesterol substitution, cholesteric hydrophobically (CH) modified pullulan (CHP), and found mainly two processes: HSA rapidly attached to the NP surface and then slowly inserted into the hydrophobic core of NPs [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

Pullulan-Based Nanoparticle-HSA Complex Formation and Drug Release Influenced by Surface Charge

et al. 2018

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The nanomaterial composition of nanoparticles and their protein adsorption in the blood is of great significance in the design of drug-loaded nanoparticles. To explore the interaction between the different surface components of nanoparticles (NPs) and protein, we synthesized three kinds of pullulan NP polymers: cholesteric hydrophobically (CH) modified pullulan (CHP), CH-modified animated pullulan (CHAP), and CH-modified carboxylated pullulan (CHSP). Pullulan NPs were prepared by the dialysis method. Dynamic light scattering was used to determine the charge and size of the three NPs. The size of NPs was altered by the number of charge groups when polymers contain the same degree of cholesterol substitution. The zeta potentials were + 12.9, − 15.4, and − 0.698 mV for CHAP, CHSP, and CHP, respectively, and the dimensions were 116.9, 156.9, and 73.1 nm, respectively. Isothermal titration calorimetry was used to determine the thermodynamic changes of NPs with different surface charge, and the effect of human serum albumin (HSA) on the titration was investigated. The changes of enthalpy and entropy demonstrated an interaction between NPs and HSA; the binding constant (Kb) for CHSP, CHP, and CHAP was 1.41, 27.7, and 412 × 104 M−1, respectively, with the positive charge for CHAP–HSA, uncharged for CHP–HSA, and negative charge for CHSP–HSA complex. Fluorescence and circular dichroism spectroscopy were used to determine the protein structure change after the complexation between NPs and HSA. The NP and HSA complexation is a complicated process composed of protein α-helical content reduction and the peptide chain extension; CHP NPs had the largest reduction in HSA α-helical content. The drug release rates of all compounds of NP and HSA were significantly lower than those of free drug and drug-loaded NPs after 48 h. The highest and lowest rates were observed in CHSP–HSA and CHP–HSA, respectively. The drug release was significantly influenced by the adsorption of HSA on NPs, and the size and surface charge of NPs played an important role in this process.

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“…The hydrophobic group cholesteryl in the CHP polymer drives the formation of the core structure of the NP, and within a certain range, the higher the degree of substitution of the hydrophobic group, the smaller the size of the NP [ 31 , 32 ]. The stability of CHPs was superior at least 2 months with no significant size and zeta potential changes, and pullulan nanoparticles can target into tumor tissue to kill cancer cell by EPR effect [ 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Delivery of Mitoxantrone with Hydrophobically Modified Pullulan Nanoparticles to Inhibit Bladder Cancer Cell and the Effect of Nano-drug Size on Inhibition Efficiency

Tao

Wen

et al. 2018

Nanoscale Res Lett

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Reducing the dosage of chemotherapeutic drugs via enhancing the delivery efficiency using novel nanoparticles has great potential for cancer treatment. Here, we focused on improving mitoxantrone delivery by using cholesterol-substituted pullulan polymers (CHPs) and selected a suitable nano-drug size to inhibit the growth of bladder cancer cells. We synthesized three kinds of CHPs, named CHP-1, CHP-2, CHP-3. Their chemical structures were identified by NMR, and the degree of cholesterol substitution was 6.82%, 5.78%, and 2.74%, respectively. Their diameters were 86.4, 162.30, and 222.28 nm. We tested the release rate of mitoxantrone in phosphate-buffered saline for 48 h: the release rate was 38.73%, 42.35%, and 58.89% for the three CHPs. The hydrophobic substitution degree in the polymer was associated with the self-assembly process of the nanoparticles, which affected their size and therefore drug release rate. The release of the three drug-loaded nanoparticles was significantly accelerated in acid release media. The larger the nanoparticle, the greater the drug release velocity. At 24 h, the IC50 value was 0.25 M, for the best inhibition of mitoxantrone on bladder cancer cells.3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) experiments demonstrated that drug-loaded CHP-3 nanoparticles with the largest size were the most toxic to bladder cancer cells. Immunofluorescence and flow cytometry revealed that drug-loaded CHP-3 nanoparticles with the largest size had the strongest effect on promoting apoptosis of bladder cancer cells. Also, the three drug-loaded nanoparticles could all inhibit the migration of MB49 cells, with large-size CHP-3 nanoparticles having the most powerful inhibition.

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The preliminary evaluation on cholesterol-modified pullulan as a drug nanocarrier

Cited by 38 publications

References 35 publications

Cholesterol-Modified Amino-Pullulan Nanoparticles as a Drug Carrier: Comparative Study of Cholesterol-Modified Carboxyethyl Pullulan and Pullulan Nanoparticles

Cholesterol-Modified Amino-Pullulan Nanoparticles as a Drug Carrier: Comparative Study of Cholesterol-Modified Carboxyethyl Pullulan and Pullulan Nanoparticles

Pullulan-Based Nanoparticle-HSA Complex Formation and Drug Release Influenced by Surface Charge

Novel Delivery of Mitoxantrone with Hydrophobically Modified Pullulan Nanoparticles to Inhibit Bladder Cancer Cell and the Effect of Nano-drug Size on Inhibition Efficiency

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