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Anti-Inflammatory Potential of Beclometasone-Loaded Filomicelles on Activated Human Monocytes
Elena Gardey1,2, Juliane Eberhardt2,3,4, Stephanie Hoeppener2
1Department of Internal Medicine IV (Gastroenterology, Hepatology, Infectious Diseases and Interdisciplinary Endoscopy), Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany.
Abstract:
Polymeric micelles with a hydrophobic core represent versatile nanostructures for encapsulation and delivery of water-insoluble drugs. Here, water-insoluble beclometasone dipropionate (BDP) which is a potent anti-inflammatory therapeutic agent but limited to topical applications so far, is encapsulated. Therefore, this work used an amphiphilic block copolymer self-assembling into flexible polymeric filomicelles, which have recently proven to selectively target inflamed areas in patients with inflammatory bowel disease (IBD). The small diameter and flexibility of these filomicelles is considered beneficial for transepithelial passages, while their length minimizes the unspecific uptake into nontargeted cells. This work successfully establishes a protocol to load the water-insoluble BDP into the core of the filomicelles, while maintaining the particle stability to prevent any premature drug release. The anti-inflammatory efficacy of BDP-loaded filomicelles is further investigated on lipopolysaccharide (LPS) stimulated human monocytes. In these ex vivo assays, the BDP-loaded filomicelles significantly reduce TNF-α, IL-6, IL-1ß, IL-12p70, IL-17a, and IL-23 release after 24 h. Additional time course study of drug-loaded filomicelles and their comparison with a common water-soluble and unspecific corticosteroid demonstrate promising results with significant immune response suppression in stimulated monocytes after 2 and 6 h. These findings demonstrate the potential of polymeric filomicelles as a vehicle for potent water-insoluble corticosteroids.
Insights
Polymeric filomicelles effectively encapsulate the anti-inflammatory drug beclometasone dipropionate (BDP). These nanostructures show promise for targeted drug delivery, significantly suppressing inflammatory markers in immune cells.
Area of Science:
- Nanotechnology
- Pharmacology
- Immunology
Background:
- Polymeric micelles are effective nanostructures for delivering hydrophobic drugs.
- Beclometasone dipropionate (BDP) is a potent anti-inflammatory drug currently limited to topical use.
- Flexible polymeric filomicelles offer targeted delivery to inflamed tissues, potentially enhancing therapeutic efficacy.
Purpose of the Study:
- To develop a protocol for loading water-insoluble BDP into polymeric filomicelles.
- To evaluate the stability and drug release characteristics of BDP-loaded filomicelles.
- To assess the anti-inflammatory efficacy of BDP-loaded filomicelles in vitro.
Main Methods:
- An amphiphilic block copolymer was used to create flexible polymeric filomicelles.
- Water-insoluble BDP was encapsulated within the hydrophobic core of the filomicelles.
- Ex vivo assays using lipopolysaccharide (LPS)-stimulated human monocytes were performed to measure cytokine release.
Main Results:
- A stable protocol for loading BDP into filomicelles was established, preventing premature drug release.
- BDP-loaded filomicelles significantly reduced the release of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-12p70, IL-17a, IL-23) from stimulated monocytes.
- Time-course studies demonstrated rapid immune response suppression by BDP-loaded filomicelles compared to a conventional corticosteroid.
Conclusions:
- Polymeric filomicelles provide a viable nanocarrier system for potent, water-insoluble anti-inflammatory drugs like BDP.
- This delivery approach shows potential for improved therapeutic outcomes in inflammatory conditions.
- Filomicelles demonstrate targeted delivery and effective suppression of inflammatory responses in immune cells.
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