Skip to main content Accesibility Help

Development and Evaluation of a Novel Topical Treatment for Acne with Azelaic Acid-Loaded Nanoparticles

  • Catarina Pinto Reis (a1), Ana Gomes (a1), Patrícia Rijo (a2), Sara Candeias (a1), Pedro Pinto (a3), Marina Baptista (a2), Nuno Martinho (a1) and Lia Ascensão (a4)...

Azelaic acid (AzA) is used in the treatment of acne. However, side effects and low compliance have been associated with several topical treatments with AzA. Nanotechnology presents a strategy that can overcome these problems. Polymeric nanoparticles can control drug release and targeting and reduce local drug toxicity. The aim of this study was to produce and evaluate an innovative topical treatment for acne with AzA-loaded poly-dl-lactide/glycolide copolymer nanoparticles. A soft white powder of nanoparticles was prepared. The mean size of loaded nanoparticles was <400 nm and zeta potential was negative. Spherical nanoparticles were observed by scanning electron microscopy. Encapsulation efficiency was around 80% and a strong interaction between the polymer and the drug was confirmed by differential scanning calorimetric analysis. In vitro drug release studies suggested a controlled and pulsatile release profile. System efficacy tests suggested similar results between the loaded nanoparticles and the nonencapsulated drug against the most common bacteria associated with acne. Cytotoxicity of AzA-loaded nanoparticles was concentration dependent, although not pronounced. The occluded patch test seemed to indicate that the formulation excipients were safe and thus AzA-loaded nanoparticles appear to be an efficient and safe treatment for acne.

Corresponding author
* Corresponding author. E-mail:
Hide All
Amichai, B., Shemer, A. & Grunwald, M.H. (2006). Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol 54(4), 644646.
Ates, O., Gürsoy, A., Altintas, H., Otük, G. & Birteksöz, S. (2003). Synthesis and antimicrobial activity of [2-[2-(N, N-disubstituted thiocarbamoyl-sulfanyl)-acylamino] thiazol-4-yl] acetic acid ethyl esters. Arch Pharm (Weinheim) 336(1), 3946.
Bojar, R., Holland, K. & Cunliffe, W. (1991). The in-vitro antimicrobial effects of azelaic acid upon Propionibacterium acnes strains P37. J Antimicrob Chemother 28(6), 843853.
Brüggemann, H., Lomholt, H.B. & Kilian, M. (2012). The flexible gene pool of Propionibacterium acnes . Mob Genet Elements 2(3), 145148.
Buzea, C., Pacheco, I.I. & Robbie, K. (2007). Nanomaterials and nanoparticles: Sources and toxicity. Biointerphases 2(4), 1771.
Casimiro, M.H., Leal, J.P., Gil, M.H. & Castro, C.A.N. (2005). Análise calorimétrica aplicada a polímeros biológicos. Parte I: Fundamentos teóricos. Bol–Soc Port Quím 98, 2936.
Charnock, C., Brudeli, B. & Klaveness, J. (2004). Evaluation of the antibacterial efficacy of diesters of azelaic acid. Eur J Pharm Sci 21(5), 589596.
Chronnell, C.M., Ghali, L.R., Ali, R.S., Quinn, A.G., Holland, D.B., Bull, J.J., Cunliffe, W.J., McKay, I.A., Philpott, M.P. & Müller-Röver, S. (2001). Human beta defensin-1 and -2 expression in human pilosebaceous units: Upregulation in acne vulgaris lesions. J Invest Dermatol 117(5), 11201125.
Clinical and Laboratory Standards Institute Guidelines (CLSI) (2011). Performance Standards for Antimicrobial Susceptibility Testing: 20th Informational Supplement. CLSI document M100-S21. Wayne, PA: CLSI.
Ganceviciene, R., Bohm, M., Fimmel, S. & Zouboulis, C.C. (2009). The role of neuropeptides in the multifactorial pathogenesis of acne vulgaris. Dermato Endocrinol 1(3), 170176.
Gollnick, H. (2003). Current concepts of the pathogenesis of acne: Implications for drug treatment. Drugs 63(15), 15791596.
Gollnick, H. & Schramm, M. (1998). Topical drug treatment in acne. Dermatology 196(1), 119125.
Gollnick, H.P., Graupe, K. & Zaumseil, R.P. (2004). Azelaic acid 15% gel in the treatment of acne vulgaris. Combined results of two double-blind clinical comparative studies. J Dtsch Dermatol Ges 2(10), 841847.
Ibrahierm, A. & Mansour, M. (2002). Simultaneous determination of azelaic and benzoic acids in topical preparations by liquid chromatography. Chromatographia 7(55), 435437.
ICH Q2 (R1) Guidelines (2005). Validation of Analytical Procedures: Text and Methodology. Geneva, Switzerland: ICH.
Jih, M.H. & Kimyai-Asadi, A. (2007). Laser treatment of acne vulgaris. Semin Plast Surg 21(3), 167174.
Kilian, M., Scholz, C.F. & Lomholt, H.B. (2012). Multilocus sequence typing and phylogenetic analysis of Propionibacterium acnes . J Clin Microbiol 50(4), 11581165.
Kinney, M.A., Yentzer, B.A., Fleischer, A.B. Jr. & Feldman, S.R. (2010). Trends in the treatment of acne vulgaris: Are measures being taken to avoid antimicrobial resistance? J Drugs Dermatol 9(5), 519524.
Knor, T., Meholjić-Fetahović, A. & Mehmedagić, A. (2011). Stratum corneum hydration and skin surface pH in patients with atopic dermatitis. Acta Dermatovenerol Croat 19(4), 242247.
Liu, C.H. & Huang, H.Y. (2012). Antimicrobial activity of curcumin-loaded myristic acid microemulsions against Staphylococcus epidermidis . Chem Pharm Bull 60(9), 11181124.
Mainardes, R., Palmira, M., Gremião, D. & Evangelista, R. (2006). Thermoanalytical study of praziquantel-loaded PLGA nanoparticles. Braz J Pharm Sci 42(4), 523530.
Makadia, H.K. & Siegel, S.J. (2011). Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers 3(3), 13771397.
Makino, K., Mogi, T., Ohtake, N., Yoshida, M., Ando, S., Nakajima, T. & Ohshima, H. (2000). Pulsatile drug release from poly (lactide-co-glycolide) microspheres: How does the composition of the polymer matrices affect the time interval between the initial burst and the pulsatile release of drugs? Colloids Surf B: Biointerfaces 19(2), 173179.
Mendham, J., Denney, R., Barnes, J. & Thomas, M. (2000). Thermal analysis. In Vogel's Textbook of Quantitative Chemical Analysis, 6th ed., Mendham, J., Denney, R.C., Barnes, J.D. & Thomas, M. (Eds.), pp. 475494. Harlow, Essex, UK: Pearson Education Limited.
Morykwas, M.J., Thornton, J.W. & Bartlett, R.H. (1987). Zeta potential of synthetic and biological skin substitutes: Effects on initial adherence. Plast Reconstr Surg 79(5), 732739.
Mukerjee, A. & Vishwanatha, J. (2009). Formulation, characterization and evaluation of curcumin-loaded PLGA nanospheres for cancer therapy. Anticancer Res 29(10), 38673875.
Nishijima, S., Kurokawa, I., Katoh, N. & Watanabe, K. (2000). The bacteriology of acne vulgaris and antimicrobial susceptibility of Propionibacterium acnes and Staphylococcus epidermidis isolated from acne lesions. J Dermatol 27(5), 318323.
Ogiso, T., Yamaguchi, T., Iwaki, M., Tanino, T. & Miyake, Y. (2001). Effect of positively and negatively charged liposomes on skin permeation of drugs. J Drug Target 9(1), 4959.
Pool, H., Quitanar, D., Figueroa, J., Mano, C., Bechara, J., Godínez, L. & Mendoza, S. (2012). Antioxidant effects of quercetin and catechin encapsulated into PLGA nanoparticles. J Nanomaterials 2012, 112.
Purdy, S., Langston, J. & Tait, L. (2003). Presentation and management of acne in primary care: A retrospective cohort study. Br J Gen Pract 53(492), 525529.
Reis, C., Martinho, N., Rosado, C., Fernandes, A. & Roberto, A. (forthcoming). Design of polymeric nanoparticles and its potential applications as drug delivery systems for acne treatment. Drug Dev Ind Pharm (in press).
Sanna, V., Roggio, A.M., Posadino, A.M., Cossu, A., Marceddu, S., Mariani, A., Alzari, V., Uzzau, S., Pintus, G. & Sechi, M. (2011). Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: Formulation, characterization, and cytotoxicity studies. Nanoscale Res Lett 6(1), 260269.
Schneider, M., Stracke, F., Hansen, S. & Schaefer, U.F. (2009). Nanoparticles and their interactions with the dermal barrier. Dermato Endocrinol 1(4), 197206.
Seidenari, S., Giusti, F. & Giovanni, P. (2000). Instrumental evaluation of occluded patch test reactions. In Handbook of Non-Invasive Methods and the Skin, Serup, J., Jemec, G.B.E. & Grave, G.L. (Eds.), pp. 973977. New York: Taylor & Francis.
Shaw, J.C. (2002). Acne: Effect of hormones on pathogenesis and management. Am J Clin Dermatol 3(8), 571578.
Siepmann, F., Le Brun, V. & Siepmann, J. (2006). Drugs acting as plasticizers in polymeric systems: A quantitative treatment. J Control Release 115(3), 298306.
Stevanovic, M., Pavlovic, V., Petkovic, J., Filipic, M. & Uskokovic, D. (2011). ROS-inducing potential, influence of different porogens and in vitro degradation of poly (D,L-lactide-co-glycolide)-based material. Express Polym Lett 5(11), 9961008.
Stinco, G., Bragadin, G., Trotter, D., Pillon, B. & Patrone, P. (2007). Relationship between sebostatic activity, tolerability and efficacy of three topical drugs to treat mild to moderate acne. J Eur Acad Dermatol Venereol 21(3), 320325.
Thiboutot, D. (2008). Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris. J Drugs Dermatol 7(1), 1316.
Thiboutot, D.M., Fleischer, A.B. Jr., Del Rosso, J.Q. & Graupe, K. (2008). Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea. J Drugs Dermatol 7(6), 541546.
Turner, N.G., Cullander, C. & Guy, R.H. (1998). Determination of the pH gradient across the stratum corneum. J Investig Dermatol Symp Proc 3(2), 110113.
USP (2007). ⟨791⟩ pH. USP 30-NF 25. Rockville, MD: U.S. Pharmacopeial.
Vasita, R., Mani, G., Agrawal, C. & Katti, D. (2010). Surface hydrophilization of electrospun PLGA micro-/nanofibers by blending with Pluronic® F-108. Polymer 51(16), 37063714.
Wolf, J.E. Jr., Kerrouche, N. & Arsonnaud, S. (2006). Efficacy and safety of once-daily metronidazole 1% gel compared with twice-daily azelaic acid 15% gel in the treatment of rosacea. Cutis 77(4), 311.
Wu, Z.M., Ling, L., Zhou, L.Y., Guo, X.D., Jiang, W., Qian, Y., Luo, K.Q. & Zhang, L.J. (2012). Novel preparation of PLGA/HP55 nanoparticles for oral insulin delivery. Nanoscale Res Lett 7(1), 299307.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Microscopy and Microanalysis
  • ISSN: 1431-9276
  • EISSN: 1435-8115
  • URL: /core/journals/microscopy-and-microanalysis
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed