Solubilization of Water-Insoluble Drugs Due to Random Amphiphilic and Degradable Poly(dimethylmalic acid) Derivatives

Schott, Marc Alexandre; Domurado, Martine; Leclercq, Laurent; Barbaud, Christel; Domurado, Dominique

doi:10.1021/bm400323c

Cited by 14 publications

(19 citation statements)

References 51 publications

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“…It was reported that the solubility of protonated CFZ under acidic conditions is 20 mg L −1 . 25 The phase solubility data based on the HPLC-UV method and 1 H NMR titration method afforded the binding constant K a of 2.66 (±0.13) × 10 4 M −1 and 3.15 (±0.16) × 10 5 M −1 , respectively. HPLC analysis is often considered as a more accurate quantification method in comparison with other means, thus we believe that the binding constant is likely in the order of magnitude of 10 4 M −1 .…”

Section: Binding Parameters Determinationmentioning

confidence: 98%

“…The improved solubility of CFZ was likely due to amine protonation under acidic conditions. 10,25,60 In the presence of CB [7] under both neutral and acidic conditions, the color of the solutions deepened significantly, which was mainly attributed to the dissolution of CFZ when complexed with CB [7] (Fig. 1).…”

Section: H Nmr Titration Of the Host-guest Complexmentioning

confidence: 99%

“…1). 25 Given that CFZ is virtually insoluble in aqueous solution, 1 H NMR titration of CFZ was performed at pD = 2 with increasing amount of CB [7] in D 2 O. However, the obtained 1 H NMR spectrum of CFZ alone ( Fig.…”

Section: H Nmr Titration Of the Host-guest Complexmentioning

confidence: 99%

“…See DOI: 10 [18][19][20][21] have been attempted to improve the solubility and minimize the side-effects of CFZ. Additionally, encapsulation by drug delivery vehicles such as amphiphilic polymers, [22][23][24][25][26] liposomes, 27,28 and macrocyclic molecules 29,30 has also been considered as a promising solution for bioavailability improvement, and to confer probable benefits on the management of side effects. Among these novel drug delivery vehicles, macrocyclic molecules have recently stimulated great interest in the pharmaceutical research field, as complexation by such molecules may not only improve the physicochemical properties of an active pharmaceutical ingredient (API), but also may modulate the biological activities of encapsulated APIs.…”

Section: Introductionmentioning

confidence: 99%

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Complexation of clofazimine by macrocyclic cucurbit[7]uril reduced its cardiotoxicity without affecting the antimycobacterial efficacy

Chan

et al. 2016

Org. Biomol. Chem.

123

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Cucurbit[7]uril (CB[7]) has recently attracted increasing attention in pharmaceutical sciences due to its great potential in improving the physicochemical properties and bioactivity of drug molecules. Herein, we have investigated the influence of CB[7]'s complexation on the solubility, antimycobacterial activity, and cardiotoxicity of a model anti-tuberculosis drug, clofazimine (CFZ), that has poor water-solubility and inherent cardiotoxicity. In our study, CFZ was found to be complexed by CB[7], in a 1 : 1 binding mode with a relatively strong binding affinity (in the order of magnitude of 10(4)-10(5) M(-1)), as determined by the phase solubility method via HPLC-UV analysis and (1)H NMR titration, as well as UV-visible spectroscopic titration, and further confirmed by electrospray ionization mass spectrometry (ESI-MS). Upon complexation, the solubility of virtually insoluble CFZ was significantly increased, reaching a concentration of up to approximately 0.53-fold of the maximum solubility of CB[7]. The inherent cardiotoxicity of CFZ was dramatically reduced to almost nil in the presence of CB[7]. Importantly, on the other hand, such a supramolecular complexation of the drug did not compromise its therapeutic efficacy, as shown by the antimycobacterial activities examined against Mycobacterium smegmatis, demonstrating the significant potential of CB[7] as a functional pharmaceutical excipient.

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Section: Binding Parameters Determinationmentioning

confidence: 98%

Section: H Nmr Titration Of the Host-guest Complexmentioning

confidence: 99%

Section: H Nmr Titration Of the Host-guest Complexmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Complexation of clofazimine by macrocyclic cucurbit[7]uril reduced its cardiotoxicity without affecting the antimycobacterial efficacy

Chan

et al. 2016

Org. Biomol. Chem.

123

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“…Studies that have been reported almost exclusively focus on enhancing the solubility of hydrophobic drugs. [23,24] …”

mentioning

confidence: 99%

Solubilisation of oils in aqueous solutions of a random cationic copolymer

Pegg

Czajka

Hazell

et al. 2017

Journal of Colloid and Interface Science

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. AbstractHypothesis. Reports of random copolymers capable of solubilising hydrophobic oils are rare. This is primarily because random copolymers are unlikely to self-assemble into suitable aggregates (or micelles) in water. A random copolymer with a "blocky" (or lumpy) microstructure may have potential to solubilise hydrophobic oils in water. This type of polymer would have advantages over block copolymers which are more laborious and costly to synthesise.Experiments. The solubilising capacity of a blocky random copolymer, namely poly(methyl methacrylate-co-2-dimethylaminoethyl methacrylate) (PMMA--co-PDMAEMA) is assessed by UV-visible spectroscopy and compared with common reference surfactants. The relative solubilising performance of random copolymers (across a narrow range of DMAEMA mol % fraction) for aromatic and aliphatic oils was also studied. The morphology of the aggregates was monitored as a function of the solubilisation capacity by small-angle neutron scattering (SANS) and dynamic-light scattering (DLS).Findings. Similarly to well-defined block copolymers, these random copolymers have a specific preference for solubilising aromatic over aliphatic oils. Increasing hydrophobicity of the copolymer enhances the solubilisation capacity. SANS has highlighted that aggregates become swollen and more uniform/spherical with increasing concentration of aromatic solubilisate, and that the aromatic solubilisate partitions throughout the random copolymer aggregates.

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Selecting and Designing Polymers Suitable for Nanoparticle Manufacturing

Cammas‐Marion

2016

Polymer Nanoparticles for Nanomedicines

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Solubilization of Water-Insoluble Drugs Due to Random Amphiphilic and Degradable Poly(dimethylmalic acid) Derivatives

Cited by 14 publications

References 51 publications

Complexation of clofazimine by macrocyclic cucurbit[7]uril reduced its cardiotoxicity without affecting the antimycobacterial efficacy

Complexation of clofazimine by macrocyclic cucurbit[7]uril reduced its cardiotoxicity without affecting the antimycobacterial efficacy

Solubilisation of oils in aqueous solutions of a random cationic copolymer

Selecting and Designing Polymers Suitable for Nanoparticle Manufacturing

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