Synthesis of a novel PEG-block-poly(aspartic acid-stat-phenylalanine) copolymer shows potential for formation of a micellar drug carrier

Prompruk, K.; Govender, Thirumala; Zhang, S.; Xiong, Chenyan; Stolnik, Snow

doi:10.1016/j.ijpharm.2005.02.025

Cited by 44 publications

(28 citation statements)

References 25 publications

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“…PASP has low toxicity, biodegradability, and biocompatibility with a peptide chain in which amide linkages extend the chain. In addition, the multifunctional characteristics of the amide linkages afford a variety of modifications by following simple chemical procedures (29). The PASP-IO nanoparticles obtained in this report had a core size of 5 nm, a hydrodynamic diameter of about 45 nm, and a saturation magnetization of about 117 emu/g of iron.…”

Section: Discussionmentioning

confidence: 89%

PET/MRI Dual-Modality Tumor Imaging Using Arginine-Glycine-Aspartic (RGD)–Conjugated Radiolabeled Iron Oxide Nanoparticles

Lee¹,

Li²,

Chen³

et al. 2008

J Nucl Med

501

393

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The purpose of this study was to develop a bifunctional iron oxide (IO) nanoparticle probe for PET and MRI scans of tumor integrin a v b 3 expression. Methods: Polyaspartic acid (PASP)-coated IO (PASP-IO) nanoparticles were synthesized using a coprecipitation method, and particle size and magnetic properties were measured. A phantom study was used to assess the efficacy of PASP-IO as a T2-weighted MRI contrast agent. PASP-IO nanoparticles with surface amino groups were coupled to cyclic arginine-glycine-aspartic (RGD) peptides for integrin a v b 3 targeting and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N9,N$,N9$,-tetraacetic acid (DOTA) chelators for PET after labeling with 64 Cu. IO nanoparticle conjugates were further tested in vitro and in vivo to determine receptor targeting efficacy and feasibility for dual PET/MRI. Results: PASP-IO nanoparticles made by single-step reaction have a core size of 5 nm with a hydrodynamic diameter of 45 6 10 nm. The saturation magnetization of PASP-IO nanoparticles is about 117 emu/g of iron, and the measured r 2 and r 2 * are 105.5 and 165.5 (sÁmM) 21 , respectively. A displacement competitive binding assay indicates that DOTA-IO-RGD conjugates bound specifically to integrin a v b 3 in vitro. Both small-animal PET and T2-weighted MRI show integrinspecific delivery of conjugated RGD-PASP-IO nanoparticles and prominent reticuloendothelial system uptake. Conclusion: We have successfully developed an IO-based nanoprobe for simultaneous dual PET and MRI of tumor integrin expression. The success of this bifunctional imaging approach may allow for earlier tumor detection with a high degree of accuracy and provide further insight into the molecular mechanisms of cancer.

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Section: Discussionmentioning

confidence: 89%

PET/MRI Dual-Modality Tumor Imaging Using Arginine-Glycine-Aspartic (RGD)–Conjugated Radiolabeled Iron Oxide Nanoparticles

Lee¹,

Li²,

Chen³

et al. 2008

J Nucl Med

501

393

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“…Since the ionization of the interacting species plays a crucial role in the formation of PIC micelles, 31 an in vitro drug release study was performed in buffers with different pH values. As shown in Figure 7, with the increase of the pH value, the micelle system displayed a rapid drug release.…”

Section: Effect Of Media Ph On Drug Releasementioning

confidence: 99%

Novel polyion complex micelles for liver‐targeted delivery of diammonium glycyrrhizinate: In vitro and in vivo characterization

Yang

Zhuo

et al. 2008

J Biomedical Materials Res

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Polyion complex micelles (PIC micelles) based on methoxy poly(ethylene glycol)-grafted-chitosan (mPEG-g-Chitosan) and lactose-conjugated PEG-grafted-chitosan (Lac-PEG-g-Chitosan) were designed as carriers for anionic drugs. Diammonium glycyrrhizinate (DG)-loaded conventional PIC micelles (mPIC micelles) and lactose-modified PIC micelles (Lac-PIC micelles) were prepared successfully with encapsulation efficiency of 97.4% and 96.7%, respectively. These micelles were uniform spherical particles with a mean size of 21.6 and 26.4 nm by transmission electron microscopy, respectively. No significant size change of these micelles in three months indicated their good physical stability. The in vitro drug release behavior of mPIC micelles in different media as well as the changes of size and zeta potential demonstrated that the drug was released mainly through swelling and diffusion induced by ion exchange. The pharmacokinetic experiments showed that the area under the curve of DG plasma concentration-time profile in rats for mPIC micelles and Lac-PIC micelles were 1.2 times and 0.4 times higher than that for DG injection, respectively. The liver targeting ability of both mPIC micelles and Lac-PIC micelles was evaluated in rats, revealing that Lac-PIC micelles could deliver more DG to liver than mPIC micelles. Therefore, the Lac-PIC micelles prepared in this study were promising liver-targeted nanocarriers for DG.

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“…In vitro, the DG release from the PIC micelles was determined using the dialysis bag method (8). PIC micelle solution (containing 100 mg P 4 and 50 mg DG) prepared under the optimized conditions was sealed in dialysis bags (MWCO, 4,000-6,000).…”

Section: In Vitro Drug Release Studymentioning

confidence: 99%

“…Generally, the charged copolymer is soluble in aqueous medium, and its chemical structure is composed of a charged segment and a neutral hydrophilic segment. The charged part of the copolymer and oppositely charged drug generate an electrostatic attraction that results in an insoluble internal core and the hydrophilic segment surrounding the core as a corona (7)(8)(9). Since PIC micelles are prepared by simply mixing the drug and polymeric solutions, this approach eliminates the need for solvents.…”

Section: Introductionmentioning

confidence: 99%

“…Since PIC micelles are prepared by simply mixing the drug and polymeric solutions, this approach eliminates the need for solvents. The interaction between drug and pendant groups on the polymer may lead to improve drug incorporation efficiency; ionic interactions also can make drug easily released from the micelles while in the case of covalent attachment and cleavage of the drug from the polymer (8).…”

Section: Introductionmentioning

confidence: 99%

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The Investigation on Polyion Complex Micelles Composed of Diammonium Glycyrrhizinate/Poly(Ethylene Glycol)–Glycidyltrimethylammonium Chloride-Grafted Polyasparthydrazide

et al. 2012

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Abstract. To prepare stable polyion complex (PIC) micelles, polyasparthydrazide (PAHy) modified with glycidyltrimethylammonium groups and methoxy poly(ethylene glycol) (mPEG) (mPEG-g-PAHy-GTA) was synthesized. The cytotoxicity of the polymer was evaluated by the methyl tetrazolium assay. The polymer entrapped the diammonium glycyrrhizinate (DG) and formed polyion complexes. The effect of pH value, grafting degree of mPEG, copolymer and drug concentration on the micelle formation was investigated by means of measuring entrapment efficiency and micelle size. In vitro DG release from the PIC micelles was detected by dialysis in various media of different ionic strengths. To examine the pharmacokinetic behavior of micelles in vivo, the time course of the drug in plasma was evaluated. The cytotoxicity of the polymer was very low. The results showed that entrapment efficiency can reach about 93%, and the mean particle size was almost 50 nm. The drug release rate decreased with a decrease in ionic strength of the release medium or an increase in the PEG grafting degree. Compared with DG solution, the AUC of DG micelles had a twofold increase. The smaller clearance and longer mean residence time of the DG micelles group compared with DG solution group showed that the DG loaded in PIC micelles can reduce drug elimination and prolong the drug residence time in the blood circulation. The results indicated that PIC micelles composed of mPEG-g-PAHy-GTA would be prospective as a drug carrier to the drugs which can be ionized in solution.

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Synthesis of a novel PEG-block-poly(aspartic acid-stat-phenylalanine) copolymer shows potential for formation of a micellar drug carrier

Cited by 44 publications

References 25 publications

PET/MRI Dual-Modality Tumor Imaging Using Arginine-Glycine-Aspartic (RGD)–Conjugated Radiolabeled Iron Oxide Nanoparticles

PET/MRI Dual-Modality Tumor Imaging Using Arginine-Glycine-Aspartic (RGD)–Conjugated Radiolabeled Iron Oxide Nanoparticles

Novel polyion complex micelles for liver‐targeted delivery of diammonium glycyrrhizinate: In vitro and in vivo characterization

The Investigation on Polyion Complex Micelles Composed of Diammonium Glycyrrhizinate/Poly(Ethylene Glycol)–Glycidyltrimethylammonium Chloride-Grafted Polyasparthydrazide

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