In vitro characterization of insulin containing thiomeric microparticles as nasal drug delivery system.

This study focused on a novel two step preparation method for the generation of insulin containing thiomer microparticles. The first step utilized the interpolymer complexation between poly(vinyl pyrrolidone) (PVP) and poly(acrylic acid) (PAA) or poly(acrylic acid)-cysteine (PAA-Cys), respectively, in the presence of insulin. Thereafter lyophilized coprecipitates were micronized via air jet mill. Particles were evaluated regarding size, morphology, insulin release and the effect on ciliary beat frequency of human nasal epithelial cells in vitro. Results displayed mean particle sizes of 2.6±1.6μm and 2.8±1.7μm for PAA/PVP/insulin and PAA-Cys/PVP/insulin microparticles, respectively, in a range where volitional impaction of particles on nasal epithelium takes place. Multi unit dosage forms showed in addition release for the incorporated insulin and nasal safety as to results of ciliary beat frequency studies (CBF). The introduced jet milled microparticles might in conclusion display a safe nasal insulin drug delivery system leading to improved absorption.

[1]  A. Bernkop‐Schnürch,et al.  Viscoelastic Properties of a New in situ Gelling Thiolated Chitosan Conjugate , 2005, Drug development and industrial pharmacy.

[2]  J. Irache,et al.  Specific and non-specific bioadhesive particulate systems for oral delivery to the gastrointestinal tract. , 1998, Advanced drug delivery reviews.

[3]  A. Bernkop‐Schnürch,et al.  Thiolated chitosan microparticles: a vehicle for nasal peptide drug delivery. , 2006, International journal of pharmaceutics.

[4]  A. Bernkop‐Schnürch,et al.  Enzymatic degradation of thiolated chitosan , 2013, Drug development and industrial pharmacy.

[5]  E. Bechgaard,et al.  Study of nasal enzyme activity towards insulin. In vitro. , 1991, Chemical & pharmaceutical bulletin.

[6]  Hoo-Kyun Choi,et al.  Mucoadhesive drug carrier based on interpolymer complex of poly(vinyl pyrrolidone) and poly(acrylic acid) prepared by template polymerization. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[7]  M. Akashi,et al.  Preparation and characterization of biodegradable nanoparticles based on poly(gamma-glutamic acid) with l-phenylalanine as a protein carrier. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[8]  C. Tribet,et al.  Effect of polyelectrolyte structure on protein-polyelectrolyte coacervates: coacervates of bovine serum albumin with poly(diallyldimethylammonium chloride) versus chitosan. , 2007, Biomacromolecules.

[9]  Helmut Werner Ott,et al.  A novel N-chlorotaurine–corticosteroid combination as a preservative-free local disinfectant: Influence on the ciliary beat frequency in vitro , 2006, Acta oto-laryngologica.

[10]  A. Bernkop‐Schnürch,et al.  Polymers with Thiol Groups: A New Generation of Mucoadhesive Polymers? , 1999, Pharmaceutical Research.

[11]  T. Kissel,et al.  Self-assembling nanocomplexes from insulin and water-soluble branched polyesters, poly[(vinyl-3-(diethylamino)- propylcarbamate-co-(vinyl acetate)-co-(vinyl alcohol)]-graft- poly(L-lactic acid): a novel carrier for transmucosal delivery of peptides. , 2004, Bioconjugate chemistry.

[12]  N. Melik-Nubarov,et al.  Relationship between the structure of amphiphilic copolymers and their ability to disturb lipid bilayers. , 2005, Biochemistry.

[13]  Y. Chien,et al.  Novel methods of insulin delivery: an update. , 1998, Critical reviews in therapeutic drug carrier systems.

[14]  P. Wüthrich,et al.  Drug/lactose co-micronization by jet milling to improve aerosolization properties of a powder for inhalation. , 2006, International journal of pharmaceutics.

[15]  A. Hickey,et al.  Aerosol Dispersion of Respirable Particles in Narrow Size Distributions Produced by Jet-Milling and Spray-Drying Techniques , 2004, Pharmaceutical Research.

[16]  Hoo-Kyun Choi,et al.  Mucoadhesive microspheres prepared by interpolymer complexation and solvent diffusion method. , 2005, International journal of pharmaceutics.

[17]  A. Bernkop‐Schnürch,et al.  Biomembrane permeability of peptides: strategies to improve their mucosal uptake. , 2002, Mini reviews in medicinal chemistry.

[18]  A. Bernkop‐Schnürch,et al.  Preparation and evaluation of microparticles from thiolated polymers via air jet milling. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[19]  A. Bernkop‐Schnürch,et al.  The Role of Glutathione in the Permeation Enhancing Effect of Thiolated Polymers , 2002, Pharmaceutical Research.

[20]  A. Bernkop‐Schnürch,et al.  Thiomers in noninvasive polypeptide delivery: in vitro and in vivo characterization of a polycarbophil-cysteine/glutathione gel formulation for human growth hormone. , 2004, Journal of pharmaceutical sciences.

[21]  A. Bernkop‐Schnürch,et al.  Thiolated polymers: self-crosslinking properties of thiolated 450 kDa poly(acrylic acid) and their influence on mucoadhesion. , 2002, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[22]  A. Bernkop‐Schnürch,et al.  Comparison of the mucoadhesive properties of various polymers. , 2005, Advanced drug delivery reviews.

[23]  K. Mantsopoulos,et al.  Intranasal complications in women with osteoporosis under treatment with nasal calcitonin spray: case reports and review of the literature. , 2008, Auris, nasus, larynx.

[24]  T. Kissel,et al.  Insulin Containing Nanocomplexes Formed by Self-Assembly from Biodegradable Amine-Modified Poly(Vinyl Alcohol)-Graft-Poly(l-Lactide): Bioavailability and Nasal Tolerability in Rats , 2005, Pharmaceutical Research.