Nanoaggregates of a random amphiphilic polyanion to carry water-insoluble clofazimine in neutral aqueous media

Hernandez-Valdepeña, Israel; Domurado, Martine; Coudane, Jean; Braud, Christian; Baussard, Jean‐François; Vert, Michel; Domurado, Dominique

doi:10.1016/j.ejps.2008.10.008

Cited by 13 publications

(19 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This possibility has been demonstrated by encapsulating clofazimine in a hydrophobized poly(methylvinylether- alt -maleic acid) (PMVEMAc). 123 Later, these authors extended this concept to biodegradable random amphiphilic polycations. 124 They prepared copolymers of of 5-Z-amino-δ-valerolactone (5-NHZVL) and ε- caprolactone (ε-CL).…”

Section: Amphiphilic Random Copolymers Based On Bio-derived Polymersmentioning

confidence: 99%

Self-assembly of random copolymers

et al. 2014

View full text Add to dashboard Cite

Self-assembly of random copolymers has attracted considerable attention recently. In this feature article, we highlight the use of random copolymers to prepare nanostructures with different morphologies and to prepare nanomaterials that are responsive to single or multiple stimuli. The synthesis of single-chain nanoparticles and their potential applications from random copolymers are also discussed in some detail. We aim to draw more attention to these easily accessible copolymers, which are likely to play an important role in translational polymer research.

show abstract

Section: Amphiphilic Random Copolymers Based On Bio-derived Polymersmentioning

confidence: 99%

Self-assembly of random copolymers

et al. 2014

View full text Add to dashboard Cite

show abstract

“…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%

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

Chan

et al. 2016

Org. Biomol. Chem.

123

View full text Add to dashboard Cite

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.

show abstract

“…Several strategies are commonly applied to improve poorly soluble drugs solubility namely prodrug formation, salt formation [6], complexation with cyclodextrins [3] or other macromolecules [1,7], formulation of amorphous dispersions [8], use of co-solvents or surfactants [9], formulation of liposomes [10] and nanosuspensions [11]. Although many types of nanoparticles are available for oral delivery, lipid nanoparticles and especially solid lipid nanoparticles (SLNs), have shown to be one of the most promising delivery systems to improve the oral bioavailability of hydrophobic drugs [12].…”

Section: Introductionmentioning

confidence: 99%

Overcoming clofazimine intrinsic toxicity: statistical modelling and characterization of solid lipid nanoparticles

Chaves

Lima

Vieira

et al. 2018

J. R. Soc. Interface.

View full text Add to dashboard Cite

The aim of this work was to develop solid lipid nanoparticles (SLNs) loaded with clofazimine (CLZ) (SLNs-CLZ) to overcome its intrinsic toxicity and low water solubility, for oral drug delivery. A Box-Behnken design was constructed to unravel the relations between the independent variables in the selected responses. The optimized SLNs-CLZ exhibited the following properties: particle size 230 nm, zeta potential of -34.28 mV, association efficiency of 72% and drug loading of 2.4%, which are suitable for oral delivery. Further characterization included Fourier transformed infrared spectroscopy that confirmed the presence of the drug and the absence of chemical interactions. By differential scanning calorimetry was verified the amorphous state of CLZ. The storage stability studies ensured the stability of the systems over a period of 12 weeks at 4°C. cytotoxicity studies evidenced no effect of both drug-loaded and unloaded SLNs on MKN-28 gastric cells and on intestinal cells, namely Caco-2 and HT29-MTX cells up to 25 µg ml in CLZ. Free CLZ solutions exhibited IC values of 16 and 20 µg ml for Caco-2 and HT29-MTX cells, respectively. It can be concluded that the optimized system, designed considering important variables for the formulation of poorly soluble drugs, represents a promising platform for oral CLZ delivery.

show abstract

Nanoaggregates of a random amphiphilic polyanion to carry water-insoluble clofazimine in neutral aqueous media

Cited by 13 publications

References 20 publications

Self-assembly of random copolymers

Self-assembly of random copolymers

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

Overcoming clofazimine intrinsic toxicity: statistical modelling and characterization of solid lipid nanoparticles

Contact Info

Product

Resources

About