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Therapeutic Efficacy of Curcumin Enhanced by Microscale Discoidal Polymeric Particles in a Murine Asthma Model.

ABSTRACT: Curcumin is considered a potential anti-asthmatic agent owing to its anti-inflammatory properties. The objective of the present study was to prepare curcumin-containing poly(lactic-co-glycolic acid)-based microscale discoidal polymeric particles (Cur-PLGA-DPPs) and evaluate their anti-asthmatic properties using a murine asthma model. Cur-PLGA-DPPs were prepared using a top-down fabrication method. The prepared Cur-PLGA-DPPs had a mean particle size of 2.5 ± 0.4 ?m and a zeta potential value of -34.6 ± 4.8 mV. Ex vivo biodistribution results showed that the Cur-PLGA-DPPs mainly accumulated in the lungs and liver after intravenous injection. Treatment with Cur-PLGA-DPPs effectively suppressed the infiltration of inflammatory cells in bronchoalveolar lavage fluid, and reduced bronchial wall thickening and goblet-cell hyperplasia compared to those in the phosphate-buffered-saline-treated control group. No significant changes in hematology and blood biochemistry parameters were observed after treatment with Cur-PLGA-DPPs. At equal curcumin concentrations, treatment with Cur-PLGA-DPPs exhibited better therapeutic efficacy than treatment with free curcumin. Our results suggest that the microscale Cur-PLGA-DPPs can be potentially used as a lung-targeted asthma therapy.

SUBMITTER: Park JY

PROVIDER: S-EPMC7463530 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Therapeutic Efficacy of Curcumin Enhanced by Microscale Discoidal Polymeric Particles in a Murine Asthma Model.

Park Jun Young JY Chu Ga Eul GE Park Sanghyo S Park Chaewon C Aryal Susmita S Kang Won Jun WJ Cho Won Gil WG Key Jaehong J

Pharmaceutics 20200806 8

Curcumin is considered a potential anti-asthmatic agent owing to its anti-inflammatory properties. The objective of the present study was to prepare curcumin-containing poly(lactic-<i>co</i>-glycolic acid)-based microscale discoidal polymeric particles (Cur-PLGA-DPPs) and evaluate their anti-asthmatic properties using a murine asthma model. Cur-PLGA-DPPs were prepared using a top-down fabrication method. The prepared Cur-PLGA-DPPs had a mean particle size of 2.5 ± 0.4 μm and a zeta potential val ...[more]

PMID: 32781576

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Project description:Fine-tuning loading and release of therapeutic and imaging agents associated with polymeric matrices is a fundamental step in the preclinical development of novel nanomedicines. Here, 1,000 × 400 nm Discoidal Polymeric Nanoconstructs (DPNs) were realized via a top-down, template-based fabrication approach, mixing together poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-diacrylate (PEG-DA) chains in a single polymer paste. Two different loading strategies were tested, namely the "direct loading" and the "absorption loading." In the first case, the agent was directly mixed with the polymeric paste to realize DPNs whereas, in the second case, DPNs were first lyophilized and then rehydrated upon exposure to a concentrated aqueous solution of the agent. Under these two loading conditions, the encapsulation efficiencies and release profiles of different agents were systematically assessed. Specifically, six agents were realized by conjugating lipid chains (DSPE) or polymeric chains (PEG) to the near-infrared imaging molecule Cy5 (DSPE-Cy5 A and DSPE-Cy5 B); the chemotherapeutic molecules methotrexate (DSPE-MTX and PEG-MTX) and doxorubicin (LA-DOX and DSPE-DOX). Moderately hydrophobic compounds with low molecular weights (MW) returned encapsulation efficiencies as high as 80% for the absorption loading. In general, direct loading was associated with encapsulation efficiencies lower than 1%. The agent hydrophobicity and MW were shown to be critical also in tailoring the release profiles from DPNs. On triple-negative breast cancer cells (MDA-MB-231), absorption loaded DOX-DPNs showed cytotoxic activities comparable to free DOX but slightly delayed in time. Preliminary in vivo studies demonstrated the high stability of Cy5-DPNs. Collectively, these results demonstrate that the pharmacological properties of DPNs can be finely optimized by changing the loading strategies (direct vs. absorption) and compound attributes (hydrophobicity and molecular weight).

Dataset Information

Therapeutic Efficacy of Curcumin Enhanced by Microscale Discoidal Polymeric Particles in a Murine Asthma Model.

Publications

Therapeutic Efficacy of Curcumin Enhanced by Microscale Discoidal Polymeric Particles in a Murine Asthma Model.

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