Strukturmodell von Polymermizellen in Abhängigkeit von der Curcumin‐Beladung mithilfe von Festkörper‐NMR‐Spektroskopie

Pöppler, Ann‐Christin; Lübtow, Michael M; Schlauersbach, Jonas; Wiest, Johannes; Meinel, Lorenz; Luxenhofer, Robert

doi:10.1002/ange.201908914

Cited by 8 publications

(3 citation statements)

References 35 publications

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“…Very recently, a solid-state NMR study revealed that the high loading of curcumin can be attributed to its interactions with the hydrophilic polymer blocks. [132] A follow-up study reported the self-assembly behavior and in vitro anticancer properties of curcumin loaded PMeOx-PPrOzi-PMeOx micelles. [133] Interestingly, the copolymer itself does not form micelles due to the low hydrophilic/hydrophobic contrast.…”

Section: Elseviermentioning

confidence: 99%

Drug Delivery Systems Based on Poly(2‐Oxazoline)s and Poly(2‐Oxazine)s

Sedláček

Hoogenboom

2019

Advanced Therapeutics

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Poly(2‐oxazoline)s (PAOx) represent an established class of polymer materials with a wide range of applications. In contrast, the homologous poly(2‐oxazine)s (PAOzi) are only gaining increasing attention in the past years. Despite their high synthetic modularity and excellent biological properties, reports describing their use as a platform for construction of drug delivery systems are still relatively sparse. In this report, an overview of the recent progress in the field of drug delivery systems based on PAOx and PAOzi polymers is provided and a comparison is made with systems based on other polymer carriers, particularly poly(ethylene glycol) (PEG) and poly(N‐hydroxypropylmethacrylamide) (PHPMA). The emerging potential of PAOx and PAOzi is highlighted in the context of current polymer therapeutics research.

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Section: Elseviermentioning

confidence: 99%

Drug Delivery Systems Based on Poly(2‐Oxazoline)s and Poly(2‐Oxazine)s

Sedláček

Hoogenboom

2019

Advanced Therapeutics

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“…We recently reported that in fact the hydrophilic corona is involved in the binding of CUR in this system. [74] Similar to the incorporation of the neat triblock copolymers, A-BuOx-A/CUR exhibited the highest gel stiffness at a given temperature, whereas G′ of A-PrOzi-A/CUR was still below that of neat H100.…”

Section: Incorporation Of Cur Nanoformulations Of Aba Triblock Copolymentioning

confidence: 89%

Combining Ultra‐High Drug‐Loaded Micelles and Injectable Hydrogel Drug Depots for Prolonged Drug Release

Lübtow

Lorson

Finger

et al. 2019

Macro Chemistry & Physics

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A compound which is particularly challenging to formulate-in form of hydrogels or otherwise-is curcumin (CUR). A plethora of preclinical studies pointed out the antioxidative, [40] cardioprotective, [41] or antitumor [42] activities of the "generally recognized as safe" (GRAS; evaluated by United States Food and Drug Administration (FDA)) [43] compound. Despite a large number of clinical trials, it has not been approved as drug for human use. Besides potentially troublesome evaluation of preclinical data, [44-47] this is most likely associated with the extremely low water solubility of 0.6 mg L −1 (1.6 µm) [48] of CUR as well as the molecules' high susceptibility to degradation, not only in water, [49,50] but also to biomedical transformations such as carbon chain cleavage, reduction, conjugation with glucuronic acid or sulfate in biological media in vitro [51] and in vivo. [52] These issues make CUR an interesting model compound to challenge hydrogels with respect to their desired application as injectable drug depot. Previously, poly(2-oxazoline) (POx) and poly(2-oxazine) (POzi)-based drug-delivery vehicles with interesting structureproperty relationships with respect to drug loading and potential for parenteral administration of CUR were reported. [53-58] The loading capacities (LCs) for CUR in ABA triblock-copolymers comprising the same hydrophilic poly(2-methyl-2-oxazoline) (PMeOx) corona (= A) and either poly(2-n-butyl-2-oxazoline) (PBuOx) (= A-BuOx-A) or (poly(2-n-propyl-2-oxazine) (PPrOzi) (= A-PrOzi-A) as hydrophobic blocks ranged from 21.6 wt% to 54.5 wt%. [53] Although benefits with respect to therapeutic efficacy of intravenously administered, ultra-high loaded A-BuOx-A/ paclitaxel formulations (LC = 45 wt%) and combination formulations of hydrophobic cis-platin prodrug and etoposide or PTX have been observed in vivo, [59-63] this might not be true for CUR due to its susceptibility to degradation or toxicity at high concentrations (not achievable orally). Inspired by CUR-loaded hydrogels for cutaneous wound repair [28] or intranasal drug delivery to the brain, [64] we wondered, if we could incorporate CUR in a recently reported, cytocompatible PMeOx-b-PPrOzi copolymerbased hydrogel, [65] for subcutaneous or intratumoral injection in order to avoid systemic circulation and/or allow prolonged release. From a more fundamental and practical point of view, it was also interesting to investigate the influence of hydrophobic CUR on the viscoelastic properties of a hydrogel that is formed based on dynamic hydrophobic interactions. Furthermore, the effect of nanoformulated CUR incorporated into the hydrogel matrix is of interest. Although drug-loaded poly mer micelles incorporated into hydrogel matrices are readily found in the literature, [17,28,29,66] such systematic investigations of the viscoelastic properties of hydrogels containing nanoformulated hydrophobic drugs are rare. In addition, to assess the potential as an injectable thermogelling drug depot, the CUR-loaded hydrogels were injected into a collag...

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“…In particular, amphiphilic triblock copolymers have been reported to exhibit very high drug loading [13][14][15][16] , while recently also gradient copolymer have been suggested [17] . The distinct macromolecular structure of POx and POzi facilitates high drug loading capacities via the high density of tertiary amides along the involvement of the hydrophilic domains of the polymer micelles [18][19][20][21] , addressing one of the critical limitations in MN-based TDDS. Moreover, their inherent stability and biocompatibility underscore their suitability for sustained drug release, ensuring a controlled pharmacological profile while minimizing systemic side effects.…”

Section: Introductionmentioning

confidence: 99%

Self-Nanoformulating Poly(2-oxazoline) and Poly(2-oxazine) Copolymers Based Amorphous Solid Dispersions as Microneedle Patch: A Formulation Study

D´Amico,

Ziegler,

Kemell

et al. 2024

Preprint

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Here, we introduce a pioneering approach in the domain of transdermal drug delivery systems (TDDS) by using microneedles (MNs) fabricated from amorphous solid dispersion comprising only a model drug and an amphiphilic block copolymer to form a drug nanoformulation upon MN dissolution. This approach presents the most minimalistic approach to maximize drug loading in MN, reaching 40 wt.%. Using scanning electron microscopy, we carefully examined the morphology of MNs across a spectrum of drug loading ratios, revealing a remarkable consistency in structure and integrity. Mechanical testing confirms the MNs' proficiency in effective skin penetration. Furthermore, a comparative study on the formation of polymeric micelles underscores the innovative concept of a “nano-in-micro drug delivery system”, offering an approach to drug release. The results demonstrate that MNs manufactured from an amorphous solid dispersion of drug and amphiphilic block copolymer with ultra-high loading, enhancing the availability and release dynamics of hydrophobic drugs, positioning them as a potent tool for enhancing TDDS. This study sets a new benchmark in the utilization of polymer-drug nanoformulations for transdermal applications and underscores the exceptional capacity for high drug loading and the creation of adaptable drug delivery mechanisms for the studied amphiphilic block copolymer.

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Strukturmodell von Polymermizellen in Abhängigkeit von der Curcumin‐Beladung mithilfe von Festkörper‐NMR‐Spektroskopie

Cited by 8 publications

References 35 publications

Drug Delivery Systems Based on Poly(2‐Oxazoline)s and Poly(2‐Oxazine)s

Drug Delivery Systems Based on Poly(2‐Oxazoline)s and Poly(2‐Oxazine)s

Combining Ultra‐High Drug‐Loaded Micelles and Injectable Hydrogel Drug Depots for Prolonged Drug Release

Self-Nanoformulating Poly(2-oxazoline) and Poly(2-oxazine) Copolymers Based Amorphous Solid Dispersions as Microneedle Patch: A Formulation Study

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