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Investigation of Polylactic Acid (PLA) Nanoparticles as Drug Delivery Systems for Local Dermatotherapy

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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.

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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).

Author information

Authors and Affiliations

  1. Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Charité-Universitätsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany

    Fiorenza Rancan, Dimitrios Papakostas, Sabrina Hadam, Wolfram Sterry, Ulrike Blume-Peytavi & Annika Vogt

  2. Photobiophysik, Institut für Physik, Humboldtd Universität Berlin, Berlin, Germany

    Steffen Hackbarth

  3. Université de Lyon, Université Lyon 1, UMR CNRS 5223 ‘IMP’, Laboratoire des Matériaux Polymères et Biomatériaux, 15 bd. André Latarjet Bât. ISTIL, F-69622, Villeurbanne Cedex, France

    Thierry Delair

  4. Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS, Lyon Cedex 07, France

    Charlotte Primard & Bernard Verrier

Authors
  1. Fiorenza Rancan
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  2. Dimitrios Papakostas
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  3. Sabrina Hadam
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  4. Steffen Hackbarth
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  5. Thierry Delair
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  6. Charlotte Primard
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  7. Bernard Verrier
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  8. Wolfram Sterry
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  9. Ulrike Blume-Peytavi
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  10. Annika Vogt
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Corresponding author

Correspondence to Annika Vogt.

Additional information

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

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