Hydrolytically Degradable Polymer Micelles for Anticancer Drug Delivery to Solid Tumors

Chytil, Petr; Etrych, Tomáš; Kostka, Libor; Ulbrich, Karel

doi:10.1002/macp.201100632

Cited by 37 publications

(70 citation statements)

References 33 publications

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“…The same polymer carriers or conjugates were used for coating biodegradable nanoparticles . Later, pH‐sensitive hydrazone spacers were introduced between a hydrophilic polymer carrier and a hydrophobic cholesterol structure to facilitate carrier elimination from the body after disintegration of the HMW micellar structure into short, water‐soluble polymer fragments in tumor tissue . Recently, a highly hydrophobic triterpenoid drug, betulinic acid, was bound to an HPMA polymer carrier by a pH‐sensitive hydrazone spacer based on 4‐oxo‐pentanoic acid .…”

Section: Hpma Copolymer‐based Drug Delivery Systems For Cancer Treatmentmentioning

confidence: 99%

“…[133,134] Later, pH-sensitive hydrazone spacers were introduced between a hydrophilic polymer carrier and a hydrophobic cholesterol structure to facilitate carrier elimination from the body after disintegration of the HMW micellar structure into short, water-soluble polymer fragments in tumor tissue. [135,136] Recently, a highly hydrophobic triterpenoid drug, betulinic acid, was bound to an HPMA polymer carrier by a pHsensitive hydrazone spacer based on 4-oxo-pentanoic acid. [137] It can be expected that the controlled drug release in the mildly acidic conditions of tumor tissue or cells will be followed by disassembly of polymer micelles, which should facilitate renal removal of the polymer carrier from the body.…”

Section: Wwwadvancedsciencenewscom Wwwmbs-journaldementioning

confidence: 99%

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HPMA Copolymer–Drug Conjugates with Controlled Tumor‐Specific Drug Release

Chytil

Koziolová

Etrych

et al. 2017

Macromolecular Bioscience

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Over the past few decades, numerous polymer drug carrier systems are designed and synthesized, and their properties are evaluated. Many of these systems are based on water‐soluble polymer carriers of low‐molecular‐weight drugs and compounds, e.g., cytostatic agents, anti‐inflammatory drugs, or multidrug resistance inhibitors, all covalently bound to a carrier by a biodegradable spacer that enables controlled release of the active molecule to achieve the desired pharmacological effect. Among others, the synthetic polymer carriers based on N‐(2‐hydroxypropyl) methacrylamide (HPMA) copolymers are some of the most promising carriers for this purpose. This review focuses on advances in the development of HPMA copolymer carriers and their conjugates with anticancer drugs, with triggered drug activation in tumor tissue and especially in tumor cells. Specifically, this review highlights the improvements in polymer drug carrier design with respect to the structure of a spacer to influence controlled drug release and activation, and its impact on the drug pharmacokinetics, enhanced tumor uptake, cellular trafficking, and in vivo antitumor activity.

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Section: Hpma Copolymer‐based Drug Delivery Systems For Cancer Treatmentmentioning

confidence: 99%

Section: Wwwadvancedsciencenewscom Wwwmbs-journaldementioning

confidence: 99%

HPMA Copolymer–Drug Conjugates with Controlled Tumor‐Specific Drug Release

Chytil

Koziolová

Etrych

et al. 2017

Macromolecular Bioscience

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“…Biodegradable polymers are of high interest in the medical field because of their potential applications in the field of tissue engineering and as drug delivery carriers [105]. Supramolecular polymers have gained much interest as potential drug delivery carriers because of their compatibility with weak water soluble compounds and their potential for controlled drug release [19,115-121]. In drug delivery systems, these polymers are designed to locally deliver active pharmaceutical ingredients to a localized place in the body, that needs the drug, and expose other parts of the body at a much lower dose.…”

Section: Clinical Applicationsmentioning

confidence: 99%

A vision for better health: Mass spectrometry imaging for clinical diagnostics

Gemperline

2013

Clinica Chimica Acta

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Background Mass spectrometry imaging (MSI) is a powerful tool that grants the ability to investigate a broad mass range of molecules from small molecules to large proteins by creating detailed distribution maps of selected compounds. Its usefulness in biomarker discovery towards clinical applications has obtained success by correlating the molecular expression of tissues acquired from MSI with well-established histology. Results To date, MSI has demonstrated its versatility in clinical applications, such as biomarker diagnostics of different diseases, prognostics of disease severities and metabolic response to drug treatment, etc. These studies have provided significant insight in clinical studies over the years and current technical advances are further facilitating the improvement of this field. Although the underlying concept is simple, factors such as choice of ionization method, sample preparation, instrumentation and data analysis must be taken into account for successful applications of MSI. Herein, we briefly reviewed these key elements yet focused on the clinical applications of MSI that cannot be addressed by other means. Conclusions Challenges and future perspectives in this field are also discussed to conclude that the ever-growing applications with continuous development of this powerful analytical tool will lead to a better understanding of the biology of diseases and improvements in clinical diagnostics.

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“…Determination of changes in particle size as well as particle concentration in the suspension has also been investigated . Assaying the degradation products is another way to study the degradation kinetics of nanoparticles . However, while these techniques can provide important information about the physicochemical characteristics of the material used, they have limited predictive value for their in vivo performance as nanocarrier drug formulations.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Evaluation of Anti‐Aggregation and Degradation Behavior of PEGylated Polymeric Nanogels under In Vivo Like Conditions

Chen

Dakwar

Braeckmans

et al. 2017

Macromolecular Bioscience

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The in vivo stability and biodegradability of nanocarriers crucially determine therapeutic efficacy as well as safety when used for drug delivery. This study aims to evaluate optimized in vitro techniques predictive for in vivo nanocarrier behavior. Polymeric biodegradable nanogels based on hydroxyethyl methacrylamide‐oligoglycolates‐derivatized poly(hydroxyethyl methacrylamide‐co‐N‐(2‐azidoethyl)methacrylamide) and with various degrees of PEGylation and crosslinking densities are prepared. Three techniques are chosen and refined for specific in vitro evaluation of the nanocarrier performance: (1) fluorescence single particle tracking (fSPT) to study the stability of nanogels in human plasma, (2) tangential flow filtration (TFF) to study the degradation and filtration of nanogel degradation products, and (3) fluorescence fluctuation spectroscopy (FFS) to evaluate and compare the degradation behavior of nanogels in buffer and plasma. fSPT results demonstrate that nanogels with highest PEGylation content show the least aggregation. The TFF results reveal that nanogels with higher crosslink density have slower degradation and removal by filtration. FFS results indicate a similar degradation behavior in human plasma as compared to that in phosphate buffered saline. In conclusion, three methods can be used to compare and select the optimal nanogel composition, and these methods hold potential to predict the in vivo performance of nanocarriers.

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Hydrolytically Degradable Polymer Micelles for Anticancer Drug Delivery to Solid Tumors

Cited by 37 publications

References 33 publications

HPMA Copolymer–Drug Conjugates with Controlled Tumor‐Specific Drug Release

HPMA Copolymer–Drug Conjugates with Controlled Tumor‐Specific Drug Release

A vision for better health: Mass spectrometry imaging for clinical diagnostics

In Vitro Evaluation of Anti‐Aggregation and Degradation Behavior of PEGylated Polymeric Nanogels under In Vivo Like Conditions

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