Colloids and Surfaces B: Biointerfaces 93 (2012) 36–40 Contents lists available at SciVerse ScienceDirect Colloids and Surfaces B: Biointerfaces j our na l ho me p age: www.elsevier.com/locate/colsurfb Chitosan-solid lipid nanoparticles as carriers for topical delivery of tretinoin Daniela M. Ridolfi a , Priscyla D. Marcato a , Giselle Z. Justo b,c , Lívia Cordi d,a , Daisy Machado b , Nelson Durán a,e,∗ a Institute of Chemistry, Biological Chemistry Laboratory, Universidade Estadual de Campinas, C.P. 6159, CEP 13083-970 Campinas, SP, Brazil b Biochemistry Department, Institute of Biology, Universidade Estadual de Campinas, Campinas, SP, Brazil c Biological Science Department (Campus Diadema) and Biochemistry Department (Campus São Paulo), Universidade Federal de São Paulo, SP, Brazil d Institute of Biology, Genetic, Evolution and Bioagents Department, Universidade Estadual de Campinas, Campinas, SP, Brazil e Center of Natural and Human Sciences, Universidade Federal do ABC, Santo André, SP, Brazil a r t i c l e i n f o Article history: Received 3 August 2011 Received in revised form 24 November 2011 Accepted 30 November 2011 Available online 17 December 2011 Keywords: All-trans retinoic acid Antibacterial activity Chitosan Cytotoxicity Solid lipid nanoparticles Tretinoin a b s t r a c t Tretinoin (TRE) or all-trans retinoic acid is employed in the topical treatment of various skin diseases including acne and psoriasis. However, its use is strongly limited by side effects and high chemical insta- bility. TRE encapsulation in nanostructured systems reduces these problems. Chitosan is a biopolymer that exhibits a number of interesting properties such as bioadhesion and antibacterial activity. The aim of this work was to prepare and characterize solid lipid nanoparticles (SLN) containing TRE, with and without addition of chitosan, to assess their in vitro cytotoxicity in keratinocytes and to evaluate their antibacterial activity against bacteria related to acne. SLN without (SLN-TRE) and with (SLN-chitosan-TRE) chitosan were prepared by hot high pressure homogenization. The hydrodynamic mean diameter and zeta potential were 162.7 ± 1.4 nm and -31.9 ± 2.0 mV for SLN-TRE, and 284.8 ± 15.0 nm and 55.9 ± 3.1 mV for SLN-chitosan-TRE. The SLN-chitosan-TRE exhibited high encapsulation efficiency, high physical stability in the tested period (one year), were not cytotoxic to keratinocytes and showed high antibacterial activity against P. acnes and S. aureus. Therefore chitosan-SLN can be good candidates to encapsulate TRE and to increase its therapeutic efficacy in the topical treatment of acne. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Tretinoin (TRE) or all-trans retinoic acid is a metabolite of Vita- min A employed in the topical treatment of various skin diseases such as acne [1], photoaging [2] and psoriasis [3]. However, its use is strongly limited by several disadvantages such as skin irritation [4] and high chemical instability [5,6]. The encapsulation of TRE in nanostructured systems has decreased the adverse effects and pro- tected this molecule against degradation. Interesting examples of these systems are liposomes [7], nanocapsules [8] and solid lipid nanoparticles (SLN) [9–15]. Results obtained by Brisaert et al. [7] showed that the incorporation of TRE in liposomes decreased its photo-degradation. Similar results were obtained with polymeric nanoparticles by Ourique et al. [8]. Shah et al. [10] incorporated TRE in SLN and also noted a significant increase in its photostability in comparison to its free form. In this same study, dermal irrita- tion tests were performed in rabbits and the formulation of TRE ∗ Corresponding author at: Instituto de Quimica, Biological Chemistry Laboratory, Universidade Estadual de Campinas, CP 6154, CEP 13083-970 Campinas, SP, Brazil. Tel.: +55 19 35213149; fax: +55 19 35213023. E-mail address: duran@iqm.unicamp.br (N. Durán). encapsulated in SLN was significantly less irritating than the com- mercial formulation of TRE. Besides providing advantages such as sustained release, protection against drug degradation and high physical stability, another important aspect of SLN is the facility to scale-up the production process, allied to the absence of organic solvents [16,17]. Chitosan is a biopolymer that has been widely used in the phar- maceutical field since it exhibits a number of interesting properties, such as bioadhesion (ability to adhere to negatively charged sur- faces such as skin and mucosa), wound-healing properties and antibacterial activity [18]. Chitosan has been used in combination with solid lipid nanoparticles to improve interaction and internal- ization in corneal cells [19], for oral administration of peptide drugs [20], to decrease SLN internalization by macrophage [21] and to enhance the oral absorption of insulin [22]. The chitosan-SLN combines the advantages of SLN with the bio- logical properties of chitosan. The bioadhesion property of chitosan can increase the retention of the drug at the site of application. Additionally, chitosan antibacterial activity is interesting for treat- ment of skin diseases involving bacterial proliferation such as acne. Therefore, the encapsulation of TRE in chitosan-SLN could increase its therapeutic efficacy in the treatment of acne, since chi- tosan antimicrobial activity would be added to the comedolytic 0927-7765/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.colsurfb.2011.11.051