Abstract
Purpose
The development of particle-based carriers for transepidermal drug delivery has become a field of major interest in dermatology. In this study, we investigated the suitability of biodegradable poly-lactic acid (PLA) particles loaded with fluorescent dyes as carriers for transepidermal drug delivery.
Methods
The penetration profiles of PLA particles (228 and 365 nm) and the release of dye from the particles were investigated in human skin explants using fluorescence microscopy, confocal laser scanning microscopy and flow cytometry.
Results
PLA particles penetrated into 50% of the vellus hair follicles, reaching a maximal depth corresponding to the entry of the sebaceous gland in 12–15% of all observed follicles. The accumulation of particles in the follicular ducts was accompanied by the release of dye to the viable epidermis and its retention in the sebaceous glands for up to 24 h. Kinetic studies in vitro as well as in skin explants revealed, that, although stable in aqueous solution, destabilization of the particles and significant release of incorporated dye occurred upon contact with organic solvents and the skin surface.
Conclusions
These results suggest that particles based on PLA polymers may be ideal carriers for hair follicle and sebaceous gland targeting.
Abbreviations
- Coum-6:
-
coumarin-6
- Coum-6_PLA_365:
-
coumarin-6-loaded 365 nm PLA particles
- CSSS:
-
cyanoacrylate skin surface stripping
- IPM:
-
isopropylmiristate
- MFI:
-
mean fluorescence intensity
- NPs:
-
nanoparticles
- NR:
-
nile red
- NR_PLA_228:
-
nile red-loaded 228 nm PLA particles
- PCL:
-
poly- ε-caprolactone
- PLA:
-
poly lactic-acid
- PLGA:
-
poly-lactic-co-glycolic acid
- SLN:
-
solid lipid nanoparticles
- VHF:
-
vellus hair follicle
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Acknowledgements
This work was partially supported by European funding to B. Verrier through the FP6 STREP Munanovac programme. C. Primard was supported by a fellowship from the Region Rhone-Alpes (France).
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Fiorenza Rancan and Dimitrios Papakosta have contributed equally to this work
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Fig S1
Cryosections of human skin after topical application of NR_PLA_228 (a-c), Coum-6_PLA_365 (d-f) and 200 nm polystyrene (PS, g-i,) particles and 16 h incubation at 37°C. Images c,f and i show the 4 time magnified image of the marked region in the corresponding sample. Most PLA particles aggregate on the follicle openings while the fluorescent dye diffused into the epidermis. On the contrary, PS particles accumulated in the follicle duct without leaking of the loaded fluorescent dye. (PPT 4160 kb)
Fig S2
NR_PLA_228 (a), Coum-6_PLA_365 (b) and polystyrene particles (c,d, Fluospheres, 200 nm) suspended in PBS were incubated 24 h with IPM. Aliquots were then collected at the PBS/IPM interface and observed with a fluorescence microscope. PLA particles form clusters at the water/IPM interface (a,b) while no clusters of PS particles were visible at the interfaces between the two phases. PS particles, in contrast, remained in dispersion in the aqueous buffer phase (c,d). (PPT 755 kb)
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Rancan, F., Papakostas, D., Hadam, S. et al. Investigation of Polylactic Acid (PLA) Nanoparticles as Drug Delivery Systems for Local Dermatotherapy. Pharm Res 26, 2027–2036 (2009). https://doi.org/10.1007/s11095-009-9919-x
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DOI: https://doi.org/10.1007/s11095-009-9919-x