ReseaRch aRticle 10.2217/NNM.10.69 © 2010 Future Medicine Ltd Nanomedicine (2010) 5(6), 843–853 ISSN 1743-5889 843 Surface-modiied PLGA-based nanoparticles that can efic iently associate and deliver virus-like particles The use of biodegradable polymeric nanoparticles for drug delivery has been gaining momentum and has shown signiicant therapeutic potential [1,2] . Over the last few years, the design of new delivery systems for immunization has received increasing interest and the support of many prominent pub- lic and private health organizations, such as the Global Alliance on Vaccines and Immunization (GAVI) and the Bill & Melinda Gates Foundation, among others. In fact, new vaccine strategies able to make vaccination campaigns easier, safer and cheaper have been prioritized and, thus, represent one of the grand challenges in global health. The development of eficient adjuvant and antigen delivery systems is a key issue in order to improve the immunogenicity of vaccines based on puriied recombinant proteins. Promising advances for improving vaccine delivery with the application of the polyester-based microparticles, such as poly(lactic acid) (PLA) and poly(d,l-lactic-co-glycolic acid) (PLGA), have been obtained either as needle-free or single-shot approaches [1,3] . A primary obstacle impeding the development of PLGA vaccine delivery systems is the instability of the antigen during the preparation of the delivery system. It has been observed that the antigens not only suffer signiicant structural alteration (i.e., denaturation, aggregation and deg- radation) during their encapsulation, but also dur- ing the course of their release from PLGA particles upon degradation of the polymer [4–7] . Therefore, several strategies aimed at preserving the antigen inside the microspheres have been developed [8–10]. Among the different approaches undertaken to overcome this problem, the most ef icient have been those based on the formation of core-coated microspheres and PLGA/poloxamer micropartic- ulate blends. In fact, these novel microstructures have been shown to provide long-lasting immune responses against tetanus toxoid [8,9] . It was evi- denced that some physicochemical characteristics of these carriers could be further optimized for better performance [11–13] . It was demonstrated that the particle size and the surface composition affect the transport of PLGA delivery systems across the mucosal surfaces. The extent of trans- porting PLGA-based delivery systems was more important for nanoparticles of 200 nm, although this could also have been inluenced by the surface characteristics of the nanoparticles, such as the presence of a hydrophilic corona, such as polyeth- yleneglycol (PEG) or chitosan (CS), which have improved the interaction of the nanoparticles with the nasal mucosa [11,14] . More recently, as another approach to solving the limitation of the internal acidiication within a nanometric structure, nanoparticles made by using an intimate blend of PLGA with polyoxyeth- ylene derivatives, either poloxamines or poloxam- ers, were developed [15] . This approach was found to be successful for preserving the biological activ- ity of plasmid DNA [16] . Furthermore, intranasal Aim: To design and develop a new nanocarrier appropriately engineered for the adequate accommodation of a virus-like particle, the recombinant hepatitis B surface antigen (22 nm), and intended to be used for the transmucosal delivery of the associated antigen. The nanoparticles consisted of a core blend of poly(D,L - lactide-co-glycolide) and poloxamer 188, and a hydrophilic shell of chitosan. Results: By by conveniently adapting the nanoprecipitation technique, it was possible to associate a signiicant amount of active antigen (44%) to the nanocarrier. The resulting nanosystems had a size of around 200 nm and positive zeta potential attributed to the association of chitosan. The nanoparticles were able to deliver the associated antigen in a controlled manner for up to 14 days without compromising its activity, as determined by ELISA. Moreover, the antigenicity of the recombinant hepatitis B surface antigen was preserved for at least 14 days, when stored as an aqueous suspension, and for at least 3 months when converted in a freeze-dried powder. Conclusion: Poly(D,L,lactic-co-glycolic acid)-based nanoparticles represent a promising approach for the delivery of virus-like-particles. KEYWORDS: PLGA-based nanoparticle n rHBsAg n surface modiication n vaccine delivery n virus-like particle Patrizia Paolicelli 1* , Cecilia Prego 1* , Alejandro Sanchez 1 & Maria J Alonso †1 1 Department of Pharmacy & Pharmaceuical Technology, School of Pharmacy, University of Saniago de Compostela, 15782 Saniago de Compostela, Spain † Author for correspondence: Tel.: +34 981 594 488 ext. 14885 Fax: +34 981 547 148 mariaj.alonso@usc.es *Authors contributed equally For reprint orders, please contact: reprints@futuremedicine.com