Chitosan-Based Nano-Embedded Microparticles: Impact of Nanogel Composition on Physicochemical Properties

Chitosan-based nanogels have been widely applied as drug delivery vehicles. Spray-drying of said nanogels allows for the preparation of dry powder nano-embedded microparticles. In this work, chitosan-based nanogels composed of chitosan, alginate, and/or sodium tri-penta phosphate were investigated, particularly with respect to the impact of composition on the resulting physicochemical properties. Different compositions were obtained as nanogels with sizes ranging from 203 to 561 nm. The addition of alginate and exclusion of sodium tri-penta phosphate led to an increase in nanogel size. The nanogels were subsequently spray-dried to form nano-embedded microparticles with trehalose or mannitol as matrix excipient. The microparticles of different composition were mostly spherical with a smooth surface and a mass median aerodynamic diameter of 6–10 µm. Superior redispersibility was observed for microparticles containing amorphous trehalose. This study demonstrates the potential of nano-embedded microparticles for stabilization and delivery of nanogel-based delivery systems.

[1]  H. M. Nielsen,et al.  Hyaluronic Acid-Based Nanogels Produced by Microfluidics-Facilitated Self-Assembly Improves the Safety Profile of the Cationic Host Defense Peptide Novicidin , 2015, Pharmaceutical Research.

[2]  L. Véron,et al.  Synthesis and structural characterization of chitosan nanogels. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[3]  M. Yeh,et al.  Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy , 2011, International journal of nanomedicine.

[4]  C. Remuñán-López,et al.  Microspheres loaded with polysaccharide nanoparticles for pulmonary delivery: preparation, structure and surface analysis , 2011 .

[5]  J. S. Dua,et al.  LIPOSOME: METHODS OF PREPARATION AND APPLICATIONS , 2012 .

[6]  N. Peppas,et al.  Hydrogels in Pharmaceutical Formulations , 1999 .

[7]  T. Park,et al.  Self-Assembled and Nanostructured siRNA Delivery Systems , 2011, Pharmaceutical Research.

[8]  Mauro Ferrari,et al.  Seven challenges for nanomedicine. , 2008, Nature nanotechnology.

[9]  C. Remuñán-López,et al.  Microspheres containing lipid/chitosan nanoparticles complexes for pulmonary delivery of therapeutic proteins. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[10]  Pharmaceutical Press,et al.  Handbook of Pharmaceutical Excipients , 2012 .

[11]  Johannes E. Schindelin,et al.  Fiji: an open-source platform for biological-image analysis , 2012, Nature Methods.

[12]  J. Zhang,et al.  Development and characterization of a novel Cremophor EL free liposome-based paclitaxel (LEP-ETU) formulation. , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[13]  Tao Wang,et al.  Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery. , 2005, Colloids and surfaces. B, Biointerfaces.

[14]  R. Neubert,et al.  Potentials of new nanocarriers for dermal and transdermal drug delivery. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[15]  T. Kissel,et al.  Surfactant-free redispersible nanoparticles in fast-dissolving composite microcarriers for dry-powder inhalation. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[16]  Laura M Ensign,et al.  Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers. , 2012, Advanced drug delivery reviews.

[17]  B. Seijo,et al.  Physicochemical characterization of chitosan nanoparticles: electrokinetic and stability behavior. , 2005, Journal of colloid and interface science.

[18]  Jinhua Hu,et al.  Stable and pH-sensitive nanogels prepared by self-assembly of chitosan and ovalbumin. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[19]  Carla P. Gomes,et al.  Translating chitosan to clinical delivery of nucleic acid-based drugs , 2014 .

[20]  Wolfgang Becker,et al.  Nanoparticles and microparticles for skin drug delivery. , 2011, Advanced drug delivery reviews.

[21]  A. Saneja,et al.  Recent Advances in Chitosan-Based Nanomedicines for Cancer Chemotherapy , 2016 .

[22]  Vladimir P Torchilin,et al.  Multifunctional nanocarriers. , 2006, Advanced drug delivery reviews.

[23]  J. Rantanen,et al.  Application of spray-drying and electrospraying/electospinning for poorly water-soluble drugs: a particle engineering approach. , 2014, Current pharmaceutical design.

[24]  R. Löbenberg,et al.  Targeted delivery of nanoparticles for the treatment of lung diseases. , 2008, Advanced drug delivery reviews.

[25]  I. El-Sherbiny,et al.  Swellable Ciprofloxacin-Loaded Nano-in-Micro Hydrogel Particles for Local Lung Drug Delivery , 2014, AAPS PharmSciTech.

[26]  Paolo Blasi,et al.  Chitosan nanoparticles: preparation, size evolution and stability. , 2013, International journal of pharmaceutics.

[27]  Christine Wandrey,et al.  Cell response to the exposure to chitosan-TPP//alginate nanogels. , 2011, Biomacromolecules.

[28]  Y. Lapitsky Ionically crosslinked polyelectrolyte nanocarriers: Recent advances and open problems , 2014 .

[29]  C. Remuñán-López,et al.  Microencapsulated chitosan nanoparticles for lung protein delivery. , 2005, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[30]  C. Remuñán-López,et al.  Microencapsulated chitosan nanoparticles for pulmonary protein delivery: in vivo evaluation of insulin-loaded formulations. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[31]  A. Bohr,et al.  Nanoembedded Microparticles for Stabilization and Delivery of Drug-Loaded Nanoparticles. , 2015, Current pharmaceutical design.

[32]  Hyejin Park,et al.  Chitosan-based nanoparticles as a sustained protein release carrier for tissue engineering applications. , 2012, Journal of biomedical materials research. Part A.

[33]  V. Préat,et al.  PLGA-based nanoparticles: an overview of biomedical applications. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[34]  Wei Xue,et al.  Novel alginate coated hydrophobically modified chitosan polyelectrolyte complex for the delivery of BSA , 2013, Journal of Materials Science: Materials in Medicine.

[35]  Ventola Cl,et al.  The nanomedicine revolution: part 1: emerging concepts. , 2012, P & T : a peer-reviewed journal for formulary management.

[36]  C. Remuñán-López,et al.  Chitosan nanoparticle-loaded mannitol microspheres: structure and surface characterization. , 2007, Biomacromolecules.

[37]  C. L. Ventola,et al.  The nanomedicine revolution: part 1: emerging concepts. , 2012, P & T : a peer-reviewed journal for formulary management.

[38]  Yuquan Wei,et al.  Preparation of alginate coated chitosan microparticles for vaccine delivery , 2008, BMC biotechnology.

[39]  R. Langer,et al.  Advances in Drug Delivery , 1986 .

[40]  A. Bohr,et al.  Preparation of nanoscale pulmonary drug delivery formulations by spray drying. , 2014, Advances in experimental medicine and biology.

[41]  Matthew J Dalby,et al.  Hydrogel nanoparticles for drug delivery. , 2013, Nanomedicine.

[42]  Rainer H Müller,et al.  Lipid nanoparticles for parenteral delivery of actives. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[43]  L. Kong,et al.  Microencapsulation of nanoparticles with enhanced drug loading for pH‐sensitive oral drug delivery for the treatment of colon cancer , 2013 .

[44]  Kinam Park,et al.  Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for oral protein delivery. , 2013, Advanced drug delivery reviews.

[45]  Wayne M. Mullett,et al.  Nanomedicine in action: an overview of cancer nanomedicine on the market and in clinical trials , 2013 .

[46]  Stefaan C. De Smedt,et al.  Cationic Polymer Based Gene Delivery Systems , 2000, Pharmaceutical Research.

[47]  Sudesh Kumar Yadav,et al.  Biodegradable polymeric nanoparticles based drug delivery systems. , 2010, Colloids and surfaces. B, Biointerfaces.

[48]  P. Cullis,et al.  Liposomal drug delivery systems: from concept to clinical applications. , 2013, Advanced drug delivery reviews.