Strategies for improving the payload of small molecular drugs in polymeric micelles

Ren, Tianyang; Gou, Jingxin; Zhang, Ling; Tao, Xutang; Tian, Bin; Yu, Daoyong; Song, Jianbo; Liu, Xiaolin; Chao, Yanhui; Xiao, Wen‐Jing; Tang, Xing

doi:10.1016/j.jconrel.2017.01.047

Cited by 101 publications

(81 citation statements)

References 126 publications

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“…[78][79][80] The core-shell structure of the polymer micelles can be varied by changing the composition of the monomers in the polymer chain. 81,82 The core of polymeric micelles is composed of densely packed polymer matrix, which can be filled with hydrophobic drugs. 83 This structure enables the polymer micelles to be utilized as suitable and effective nanocarriers.…”

Section: Polymeric Micellesmentioning

confidence: 99%

Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy

Zhang¹,

Tang²,

Liu³

et al. 2017

IJN

128

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Chemotherapy is still one of the main cancer therapy treatments, but the curative effect of chemotherapy is relatively low, as such the development of a new cancer treatment is highly desirable. The gradual maturation of nanotechnology provides an innovative perspective not only for cancer therapy but also for many other applications. There are a diverse variety of nanoparticles available, and choosing the appropriate carriers according to the demand is the key issue. The performance of nanoparticles is affected by many parameters, mainly size, shape, surface charge, and toxicity. Using nanoparticles as the carriers to realize passive targeting and active targeting can improve the efficacy of chemotherapy drugs significantly, reduce the mortality rate of cancer patients, and improve the quality of life of patients. In recent years, there has been extensive research on nanocarriers. In this review, the effects of several major parameters of nanoparticles on their physical and chemical properties are reviewed, and then the recent progress in the application of several commonly used nanoparticles is presented.

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Section: Polymeric Micellesmentioning

confidence: 99%

Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy

Zhang¹,

Tang²,

Liu³

et al. 2017

IJN

128

View full text Add to dashboard Cite

show abstract

“…argued that the low drug loading capacity and poor in vivo stability typically displayed by polymeric micelles is responsible for this major discrepancy. [10] These major problems concerning nanoformulations, drug delivery and the advancement of polymeric micelles for clinical cancer therapy were also critically reviewed by other researchers. [11][12][13] Polymer micelles comprising a poly(2-oxazoline) (POx) based amphiphilic triblock copolymer (poly(2-methyl-2-oxazoline)-block-poly(2-butyl-2-oxazoline)-block-poly(2-methyl-2oxazoline) (PMeOx-b-PBuOx-b-PMeOx ≡ A-pBuOx-A)) constitute an unusual exception.…”

Section: Introductionmentioning

confidence: 99%

Investigating the Influence of Aromatic Moieties on the Formulation of Hydrophobic Natural Products and Drugs in Poly(2-oxazoline)-Based Amphiphiles

et al. 2018

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Many natural compounds with interesting biomedical properties share one physicochemical property, namely, low water solubility. Polymer micelles are, among others, a popular means to solubilize hydrophobic compounds. The specific molecular interactions between the polymers and the hydrophobic drugs are diverse, and recently it has been discussed that macromolecular engineering can be used to optimize drug-loaded micelles. Specifically, π-π stacking between small molecules and polymers has been discussed as an important interaction that can be employed to increase drug loading and formulation stability. Here, we test this hypothesis using four different polymer amphiphiles with varying aromatic content and various natural products that also contain different relative amounts of aromatic moieties. In the case of paclitaxel, having the lowest relative content of aromatic moieties, the drug loading decreases with increasing relative aromatic amount in the polymer, whereas the drug loading of curcumin, having a much higher relative aromatic content, is increased. Interestingly, the loading using schizandrin A, a dibenzo[ a, c]cyclooctadiene lignan with intermediate relative aromatic content is not influenced significantly by the aromatic content of the polymers employed. The very high drug loading, long-term stability, ability to form stable highly loaded binary coformulations in different drug combinations, small-sized formulations, and amorphous structures in all cases corroborate earlier reports that poly(2-oxazoline)-based micelles exhibit an extraordinarily high drug loading and are promising candidates for further biomedical applications. The presented results underline that the interaction between the polymers and the incorporated small molecules may be more complex and are significantly influenced by both sides, the used carrier and drug, and must be investigated in each specific case.

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“…11 Unfortunately, these formulations are often plagued with a low drug loading and instability in vivo. [12][13][14] Strategies to circumvent this limitation include adjustment of the hydrophobic-hydrophilic balance, [15][16][17] improvement of the polymer-drug interactions, [18][19][20][21] cross-linking, [22][23][24][25] or conjugation of the drug to the polymer via covalent bonding. 15,[26][27][28][29] However, these strategies are often met with challenges, particularly slow, insufficient release.…”

Section: Introductionmentioning

confidence: 99%

Bile Acid-Based Drug Delivery Systems for Enhanced Doxorubicin Encapsulation: Comparing Hydrophobic and Ionic Interactions in Drug Loading and Release

et al. 2018

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Doxorubicin (Dox) is a drug of choice in the design of drug delivery systems directed toward breast cancers, but is often limited by loading and control over its release from polymer micelles. Bile acid-based block copolymers present certain advantages over traditional polymer-based systems for drug delivery purposes, since they can enable a higher drug loading via the formation of a reservoir through their aggregation process. In this study, hydrophobic and electrostatic interactions are compared for their influence on Dox loading inside cholic acid based block copolymers. Poly(allyl glycidyl ether) (PAGE) and poly(ethylene glycol) (PEG) were grafted from the cholic acid (CA) core yielding a star-shaped block copolymer with 4 arms (CA-(PAGE- b-PEG)) and then loaded with Dox via a nanoprecipitation technique. A high Dox loading of 14 wt % was achieved via electrostatic as opposed to hydrophobic interactions with or without oleic acid as a cosurfactant. The electrostatic interactions confer a pH responsiveness to the system. 50% of the loaded Dox was released at pH 5 in comparison to 12% at pH 7.4. The nanoparticles with Dox loaded via hydrophobic interactions did not show such a pH responsiveness. The systems with Dox loaded via electrostatic interactions showed the lowest IC and highest cellular internalization, indicating the pre-eminence of this interaction in Dox loading. The blank formulations are biocompatible and did not show cytotoxicity up to 0.17 mg/mL. The new functionalized star block copolymers based on cholic acid show great potential as drug delivery carriers.

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Strategies for improving the payload of small molecular drugs in polymeric micelles

Cited by 101 publications

References 126 publications

Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy

Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy

Investigating the Influence of Aromatic Moieties on the Formulation of Hydrophobic Natural Products and Drugs in Poly(2-oxazoline)-Based Amphiphiles

Bile Acid-Based Drug Delivery Systems for Enhanced Doxorubicin Encapsulation: Comparing Hydrophobic and Ionic Interactions in Drug Loading and Release

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