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Targeting of microdiscs in white cells to tibial abscesses in rabbits
M Bhamra1, M R Tyrrell, A L Hulme
1Academic Surgical Unit, Queen Elizabeth the Queen Mother Wing, St Mary's Hospital, London, England.
Abstract:
The ability to deliver drugs to specific foci of infection is a sought-after goal. One solution is to use microparticles as drug carriers. This approach is limited by detection of microparticles by the reticuloendothelial system (RES). In order to reduce RES uptake of such particles, we investigated the possibility of "hiding" microparticles within white cells prior to targeting them to experimental tibial abscesses. We used radioactive silicone microdiscs, supplied by the Royal Signals & Radar Establishment. Twelve rabbits with abscesses in the right tibia were used: six control animals received radioactive opsonised microdiscs intravenously, and six animals received the same dose of microdiscs following incubation of the microdiscs with white cells. Each animal's liver, spleen, lungs, and both tibiae were removed, weighed, and homogenised. Radioactivity counts were obtained from each tissue, and the ratio of counts per gram of tissue for the right/left tibiae was calculated for the two groups of animals. The ratio of counts in the control group was 1.66 (+/- 0.57 SD), and the mean ratio of counts from the rabbits who had microdisc incubated with white cells was 3.32 (+/- 0.52 SD). This difference was statistically significant at p = 0.02 (Mann-Whitney U test).
Insights
Researchers hid microparticles within white blood cells to improve drug delivery to infection sites. This method significantly increased microparticle accumulation in tibial abscesses compared to conventional delivery, overcoming reticuloendothelial system detection.
Area of Science:
- Biomedical Engineering
- Drug Delivery Systems
- Immunology
Background:
- Targeted drug delivery to infection foci is challenging.
- Microparticles are potential drug carriers but are often detected by the reticuloendothelial system (RES).
- Reducing RES uptake is crucial for effective microparticle-based therapies.
Purpose of the Study:
- To investigate if encapsulating microparticles within white blood cells can reduce RES uptake.
- To assess the efficacy of white blood cell-mediated delivery of microparticles to experimental tibial abscesses.
Main Methods:
- Radioactive silicone microdiscs were used as model drug carriers.
- Twelve rabbits with tibial abscesses were divided into two groups: control (intravenous microdiscs) and experimental (microdiscs incubated with white blood cells).
- Tissue radioactivity was measured to determine microparticle distribution, focusing on the ratio of counts in the infected vs. contralateral tibia.
Main Results:
- The ratio of radioactivity in the infected tibia to the contralateral tibia was significantly higher in the group receiving white blood cell-incubated microdiscs (3.32 +/- 0.52 SD) compared to the control group (1.66 +/- 0.57 SD).
- This difference was statistically significant (p = 0.02).
- This suggests enhanced targeting of abscesses when microparticles are shielded by white blood cells.
Conclusions:
- Encapsulating microparticles within white blood cells is a promising strategy to evade RES detection.
- This approach can significantly improve the accumulation of drug carriers at infection sites.
- White blood cell-mediated delivery offers a potential solution for enhancing the efficacy of microparticle-based therapeutics.
