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In Vitro and In Vivo Studies on HPMA-Based Polymeric Micelles Loaded with Curcumin.

ABSTRACT: Curcumin-loaded polymeric micelles composed of poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) were prepared to solubilize and improve the pharmacokinetics of curcumin. Curcumin-loaded micelles were prepared by a nanoprecipitation method using mPEG_5kDa-b-p(HPMA-Bz) copolymers with varying molecular weight of the hydrophobic block (5.2, 10.0, and 17.1 kDa). At equal curcumin loading, micelles composed of mPEG_5kDa-b-p(HPMA-Bz)_17.1kDa showed better curcumin retention in both phosphate-buffered saline (PBS) and plasma at 37 °C than micelles based on block copolymers with smaller hydrophobic blocks. No change in micelle size was observed during 24 h incubation in plasma using asymmetrical flow field-flow fractionation (AF₄), attesting to particle stability. However, 22-49% of the curcumin loading was released from the micelles during 24 h from formulations with the highest to the lowest molecular weight p(HPMA-Bz), respectively, in plasma. AF₄ analysis further showed that the released curcumin was subsequently solubilized by albumin. In vitro analyses revealed that the curcumin-loaded mPEG_5kDa-b-p(HPMA-Bz)_17.1kDa micelles were internalized by different types of cancer cells, resulting in curcumin-induced cell death. Intravenously administered curcumin-loaded, Cy7-labeled mPEG_5kDa-b-p(HPMA-Bz)_17.1kDa micelles in mice at 50 mg curcumin/kg showed a long circulation half-life for the micelles (t_1/2 = 42 h), in line with the AF₄ results. In contrast, the circulation time of curcumin was considerably shorter than that of the micelles (t_1/2? = 0.11, t_1/2? = 2.5 h) but ?5 times longer than has been reported for free curcumin (t_1/2? = 0.02 h). The faster clearance of curcumin in vivo compared to in vitro studies can be attributed to the interaction of curcumin with blood cells. Despite the excellent solubilizing effect of these micelles, no cytostatic effect was achieved in neuroblastoma-bearing mice, possibly because of the low sensitivity of the Neuro2A cells to curcumin.

SUBMITTER: Bagheri M

PROVIDER: S-EPMC7927141 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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In Vitro and In Vivo Studies on HPMA-Based Polymeric Micelles Loaded with Curcumin.

Bagheri Mahsa M Fens Marcel H MH Kleijn Tony G TG Capomaccio Robin B RB Mehn Dora D Krawczyk Przemek M PM Scutigliani Enzo M EM Gurinov Andrei A Baldus Marc M van Kronenburg Nicky C H NCH Kok Robbert J RJ Heger Michal M van Nostrum Cornelus F CF Hennink Wim E WE

Molecular pharmaceutics 20210119 3

Curcumin-loaded polymeric micelles composed of poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) were prepared to solubilize and improve the pharmacokinetics of curcumin. Curcumin-loaded micelles were prepared by a nanoprecipitation method using mPEG5kDa-b-p(HPMA-Bz) copolymers with varying molecular weight of the hydrophobic block (5.2, 10.0, and 17.1 kDa). At equal curcumin loading, micelles composed of mPEG5kDa</s ...[more]

PMID: 33464911

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Project description:Micelles composed of block copolymers of poly(ethylene glycol)- b-poly( N-2-benzoyloxypropyl methacrylamide) (mPEG- b-p(HPMA-Bz)) have shown great promise as drug-delivery carriers due to their excellent stability and high loading capacity. In the present study, parameters influencing micelle size were investigated to tailor sizes in the range of 25-100 nm. Micelles were prepared by a nanoprecipitation method, and their size was modulated by the block copolymer properties such as molecular weight, their hydrophilic-to-hydrophobic ratio, homopolymer content, as well as formulation and processing parameters. It was shown that the micelles have a core-shell structure using a combination of dynamic light scattering and transmission electron microscopy analysis. By varying the degree of polymerization of the hydrophobic block ( NB) between 68 and 10, at a fixed hydrophilic block mPEG5k ( NA = 114), it was shown that the hydrophobic core of the micelle was collapsed following the power law of ( NB × Nagg)1/3. Further, the calculated brush height was similar for all the micelles examined (10 nm), indicating that crew-cut micelles were made. Both addition of homopolymer and preparation of micelles at lower concentrations or lower rates of addition of the organic solvent to the aqueous phase increased the size of micelles due to partitioning of the hydrophobic homopolymer chains to the core of the micelles and lower nucleation rates, respectively. Furthermore, it was shown that by using different solvents, the size of the micelles substantially changed. The use of acetone, acetonitrile, ethanol, tetrahydrofuran, and dioxane resulted in micelles in the size range of 45-60 nm after removal of the organic solvents. The use of dimethylformamide and dimethylsulfoxide led to markedly larger sizes of 75 and 180 nm, respectively. In conclusion, the results show that by modulating polymer properties and processing conditions, micelles with tailorable sizes can be obtained.

Dataset Information

In Vitro and In Vivo Studies on HPMA-Based Polymeric Micelles Loaded with Curcumin.

Publications

<i>In Vitro</i> and <i>In Vivo</i> Studies on HPMA-Based Polymeric Micelles Loaded with Curcumin.

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