Research Paper Chitosan based micro- and nanoparticles for colon-targeted delivery of vancomycin prepared by alternative processing methods T. Cerchiara a,⇑ , A. Abruzzo a , M. di Cagno b , F. Bigucci a , A. Bauer-Brandl b , C. Parolin a , B. Vitali a , M.C. Gallucci c , B. Luppi a a Department of Pharmacy and Biotechnologies, University of Bologna, Via San Donato 19/2, 40127 Bologna, Italy b Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark c Department of Chemistry and Chemical Technologies, University of Calabria, Via P. Bucci, 87036 Arcavacata di Rende (CS), Italy article info Article history: Received 3 July 2014 Revised 26 November 2014 Accepted in revised form 3 March 2015 Available online 11 March 2015 Keywords: Microparticles Nanoparticles Drug delivery Chitosan Vancomycin abstract The aim of this work was to prepare chitosan (CH) based particulate formulations for colon delivery of vancomycin (VM). Chitosan microparticles (MPs) and nanoparticles (NPs) loaded with VM were prepared using different CH/tripolyphosphate (TPP) molar ratios and different technological processes. In particu- lar, nanoparticles were prepared by ionic gelation and freeze-drying to recover these particles, or, alternatively, by spray-drying method. Microparticles were prepared using a different spray-dryer. Micro- and nanoparticles were characterized in terms of size distributions by photon correlation spec- troscopy (PCS), while encapsulation and drug loading efficiencies were studied using a dialysis method. Fourier Transform Infrared Spectroscopy (FT-IR) was employed to determine the surface composition of the micro- and nanoparticles respectively, and the morphologies of the developed systems were studied by scanning electron microscopy (SEM). Water uptake as well as drug release profiles were also mea- sured. Antibacterial activity against Staphylococcus aureus, a Gram-positive model strain, was evaluated. FT-IR results suggested an electrostatic interaction between VM and CH/TPP particles. Moreover, the particles were found to hold a positive zeta-potential, indicating the presence of CH on the particle sur- faces. Particle size and encapsulation efficiency were mainly influenced by the different manufacturing processes employed. Nanoparticles obtained by spray-drying showed the best results in terms of water uptake and drug release rate. Moreover, they showed a good bactericidal activity against S. aureus. Ó 2015 Elsevier B.V. All rights reserved. 1. Introduction It has recently been demonstrated that micro/nanoparticles based on chitosan can be suitable delivery systems for oral site-specific drug delivery [1]. Chitosan (CH) is a natural linear polycationic polysaccharide obtained by partial N-deacetylation of chitin; it shows interesting properties such as biocompatibility, biodegradability and mucoadhesion and it has been widely used to prepare various oral drug delivery systems [2]. In particular, in the last years chitosan particles have been developed as new dosage forms for the treatment of colonic diseases such as ulcera- tive colitis, Crohn’s disease, pseudomembranous colitis and irrita- ble bowel syndrome [3,4], confirming chitosan’s ability to enhance drug absorption and to improve drug bioavailability. Vancomycin (VM) is an antibiotic glycopeptide used in the prophylaxis and treatment of serious infections such as the pseu- domembranous colitis caused by Clostridium difficile [5] and of other pathologies caused by Gram-positive bacteria e.g. Staphylococcus aureus and other Staphylococcus species that are unresponsive to other antibiotics [6]. Nevertheless, the oral administration pathway of VM is mainly limited by degradation in the acidic environment of the stomach, by enzymatic degrada- tion, by low epithelial permeability, and by rapid clearance from the gastrointestinal tract. For this reason, VM needs to be admi- nistered intravenously for systemic therapy and it is associated with severe adverse effects [7]. To increase VM’s oral bioavailability, micro/nanoparticles based on chitosan/pectin [8,9] and macrogel-based solid dispersion beads [5] have been developed. In particular, nanoparticles possess sev- eral advantages over other forms of conventional delivery systems such as tablets and capsules. The size of particles plays an impor- tant role in colon-targeted delivery: small particles can better attach to mucus layers due to their easier penetration and their relatively small mass. Moreover, nanoparticle accumulation could http://dx.doi.org/10.1016/j.ejpb.2015.03.004 0939-6411/Ó 2015 Elsevier B.V. All rights reserved. ⇑ Corresponding author at: Dpt. Pharmacy and Biotechnology, Bologna University, Via San Donato 19/2, 48127 Bologna, Italy. Tel.: +39 (0)51 20 95615. E-mail address: teresa.cerchiara2@unibo.it (T. Cerchiara). European Journal of Pharmaceutics and Biopharmaceutics 92 (2015) 112–119 Contents lists available at ScienceDirect European Journal of Pharmaceutics and Biopharmaceutics journal homepage: www.elsevier.com/locate/ejpb