pH-responsive, lysine-based hydrogels for the oral delivery of a wide size range of molecules

Watkins, Kira A.; Chen, Rongjun

doi:10.1016/j.ijpharm.2014.12.005

Cited by 35 publications

(26 citation statements)

References 36 publications

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“…small molecules, viruses, antibodies, plasmids, proteins), pH-sensitivity to regions of the gastrointestinal tract and good oral delivery. 280,286–289 Such gene delivery platforms can be also envisioned for clinical applications. 280 …”

Section: Different Stimuli-responsive Mnpsmentioning

confidence: 99%

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

et al. 2016

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New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive “smart” MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.

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Section: Different Stimuli-responsive Mnpsmentioning

confidence: 99%

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

et al. 2016

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“…Table gives various hydrogel formulae used in this study. For all hydrogels, the molar ratio of crosslinkers and polymer residuals was kept constant according to previous optimization . As the polymer concentration decreased from 10.0 wt% to 2.5 wt%, the solid contents of hydrogels decreased from 7.5 wt% to 4.3 wt%.…”

Section: Resultsmentioning

confidence: 99%

“…Though all components of these hydrogels were reported as biocompatible, the AlamarBlue assay was carried out to evaluate hydrogels' cytotoxicity, by measuring the variations of the metabolic activity of Hela cells treated with different gel concentrations. As shown in Figure d, the viabilities of the cells were all higher than 90% at the gel concentration up to 5 mg mL −1 , indicating that all those hydrogels had negligible cytotoxicity.…”

Section: Resultsmentioning

confidence: 99%

“…The pseudo‐peptidic polymer is easy‐to‐synthesize and each structural unit contains one pendant carboxylic acid group available for pH‐responsive functionalities and further modifications. Its constituent components, lysine and isophthalic acid, have low toxicity and do not accumulate in the body, and it has been previously employed to prepare hydrogel systems with pH‐triggered controlled release of model drugs over a wide size range (0.3–2000 kDa) . In this paper, PLP was crosslinked by CDE, an amino acid derivative bearing a disulfide bond.…”

Section: Introductionmentioning

confidence: 99%

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Amino Acid Based Hydrogels with Dual Responsiveness for Oral Drug Delivery

Wang

Liu

Villar‐García

et al. 2016

Macromolecular Bioscience

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Abstract:This study reports a series of novel amino acid-based dual-responsive hydrogels prepared through a simple one-pot EDC coupling reaction. The solid content, structure and mechanical behavior of the hydrogels could be easily adjusted by changing the concentrations of the polymers and the crosslinkers. With pH-responsive anionic pseudo-peptides as backbones and disulfide-containing L-cystine dimethyl ester as crosslinkers, these hydrogels collapsed and formed relatively compact structure at an acidic pH, while swelled and partly dissociated at a neutral pH. Further addition of dithiothreitol (DTT) facilitated complete degradation of the hydrogels. The high loading efficiency, rapid but complete triggered-release and good biocompatibility make these hydrogels promising candidates for oral delivery.Additional Information:Question ResponsePlease submit a plain text version of your cover letter here.Please note, if you are submitting a revision of your manuscript, there is an opportunity for you to provide your responses to the reviewers later; please do not add them to the cover letter.Please see the attached Cover Letter. This study reports a series of novel amino acid-based dual-responsive hydrogels. Prepared by a facile one-pot EDC coupling reaction, the solid content, structure and mechanical behavior of hydrogels could be easily adjusted by changing the concentrations of the polymers and the crosslinkers. With pH-responsive anionic pseudo-peptides as backbones and disulfidecontaining L-cystine dimethyl ester as crosslinkers, these hydrogels are able to collapse and form relatively compact structure at an acidic pH, while swelled and partly dissociated at a neutral pH. Further addition of DTT facilitated complete degradation of hydrogels. The high loading efficiency, rapid but complete triggered-release and good biocompatibility make these hydrogels promising candidates for oral delivery.

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“…It has been developed poly mers based on amino acids with good biocompati bility like hydrogel based on poly γ-glutamic acid (γ-PGA) and ε-polylysine (ε-PL) or able to adsorb rare earth elements like sodium alginate hydrogel linked with poly-γ-glutamate [2,3]. Scientists also developed specific polymers for drug delivery, for example lysinebased hydrogels for the oral delivery which are pHsensitive or safe detoxifying agent like poly(γ-glutamic acid) [4,5]. We develop and research polymers based on pseudopolyamino acids which, like polymers based on amino acids, have good bio compatibility but are more stable for degradation.…”

mentioning

confidence: 99%

Characteristics of novel polymer based on pseudo-polyamino acids GluLa-DPG-PEG600: binding of albumin, biocompatibility, biodistribution and potential crossing the blood-brain barrier in rats

Chekh¹,

Ferens²,

Остапів³

et al. 2017

Ukr.Biochem.J.

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the aim of our work was to study biological properties of the polymer based on pseudo-polyamino acids GluLa-DPG-PEG600, its ability to bind albumin, as well as its localization in rat body and influence onN owadays, one of the main task for phar macy is development a novel polymeric compounds for drug delivery and other biomedical purposes [1]. It has been developed poly mers based on amino acids with good biocompati bility like hydrogel based on poly γ-glutamic acid (γ-PGA) and ε-polylysine (ε-PL) or able to adsorb rare earth elements like sodium alginate hydrogel linked with poly-γ-glutamate [2,3]. Scientists also developed specific polymers for drug delivery, for example lysinebased hydrogels for the oral delivery which are pHsensitive or safe detoxifying agent like poly(γ-glutamic acid) [4,5]. We develop and research polymers based on pseudopolyamino acids which, like polymers based on amino acids, have good bio compatibility but are more stable for degradation.Pseudo-polyamino acids -class of polymeric compounds based on natural amino acids. Their structure doesn't contain peptide bonds, ones can be changed to urethane, ester, anhydrite and other chemical bonds [6]. Drug delivery systems based on pseudopolyamino acids with ester bonds are re spectable for research and developing. Pseudo-poly amino acids based on glycine, asparagine, arginine and lysine in complex with lactic acid are biodegra dable and have advanced cell adhesion [7][8][9]. Pseu dopolyamino acids based on tyrosine in complexes with ZnO can be used in anticancer therapy [10,11]. The main advantages of this class of polymers as drug transporters are their biodegradability and prolonged time of degradation that correlates with releasing of drugs active components (for example, polymers based on glycine and lactic acid are de composed for about 10 weeks) [7,8]. Polymer Glu La-DPG-PEG600 based on glutamic acid with ester bonds was developed. Therefore, the main purpose

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pH-responsive, lysine-based hydrogels for the oral delivery of a wide size range of molecules

Cited by 35 publications

References 36 publications

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

Amino Acid Based Hydrogels with Dual Responsiveness for Oral Drug Delivery

Characteristics of novel polymer based on pseudo-polyamino acids GluLa-DPG-PEG600: binding of albumin, biocompatibility, biodistribution and potential crossing the blood-brain barrier in rats

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