Gelatin/chitosan particles suitable for application in ocular drug administration were prepared by a two-step cross-linking process performed in an emulsion-phase separation system. The particles were characterized by scanning electron microscopy and laser diffractometry, and the diameters were 0.202—4.596 µm. The microparticles pH-dependent behavior was monitored by their mean diameter changes in aqueous environment. Adrenalin was drug used to study loading and release characteristics. The prepared particles were nontoxic, with the DL50 values of 6.9—8.19 g/kg body mass. The in vivo biocompatibility tests consisted of subcutaneous administration of a microparticle suspension in physiological serum followed by morpho histological analysis of the implantation site. The in vivo adrenalin ocular delivery was tested on both animals and a voluntary human patient to determine the adrenalin action and by tears. The particles showed good adherent properties without irritation to the patient; adrenalin was released cleared the ocular congestion.
De Campos, A.M. , Sanchez, A. and Alonso, M.J. (2001). Chitosan Nanoparticles: A New Vehicle for the Improvement of the Delivery of Drugs to the Ocular Surface. Application to Cyclosporin A, Int. J. Pharm., 224: 159-168.
2.
Felt, O., Furrer, P., Mayer, J.M., Plazonnet, B., Buri, P. and Gurny, R. ( 1999). Topical Use of Chitosan in Ophthalmology: Tolerance Assessment and Evaluation of Precorneal Retention, Int. J. Pharm., 180: 185-193.
3.
Calvo, P., Vila-Jato, J.L. and Alonso, M.J. ( 1997). Evaluation of Cationic Polymer-Coated Nanocapsules as Ocular Drug Carriers, Int. J. Pharm., 153: 41-50.
4.
Carrino-Gomez, B. and Duncan, R. (1997). Evaluation of the Biological Properties of Soluble Chitosan and Chitosan Microspheres, Int. J. Pharm., 148: 231-240.
5.
Thanou, M., Verhoef, J.C. and Junginger, H.E. ( 2001). Oral Drug Absorption Enhancement by Chitosan and Its Derivatives, Adv. Drug. Delivery. Rev., 52: 117-126.
6.
Genita, I., Perugini, P., Conti, B. and Pavanetto, F. ( 1997). A Multiple Emulsion Method to Entrap a Lipophilic Compound Into Chitosan Microspheres, Int. J. Pharm., 152: 237-246.
7.
Perugini, P. , Genta, I., Pavanetto, F., Conti, B., Scalia, S. and Baruffini, A. (2000). Study on Glycolic Acid Delivery by Liposomes and Microspheres, Int. J. Pharm., 196: 51-61.
8.
Filipovic-Grcic, J., Voinovich, D., Moneghini, M., Becirevic-Lacan , M., Magarotto, L. and Jalsenjak, I. (2000). Chitosan Microspheres With Hydrocortisone and Hydrocortisone-hydroxypropyl-β-cyclodextrin Inclusion Complex, Eur. J. Pharm. Sci., 9: 373-379.
9.
He, P., Davis, S.S. and Illum, L. ( 1999). Chitosan Microspheres Prepared by Spray Drying, Int. J. Pharm., 187: 53-65.
10.
Berger, J., Reist, M., Mayer, J.M., Felt, O., Peppas, N.A. and Gurny, R. ( 2004). Structure and Interactions in Covalently and Ionically Crosslinked Chitosan Hydrogels for Biomedical Applications, Eur. J. Pharm. Biopharm., 57: 19-34.
11.
Berthold, A. , Cremer, K. and Kreuter, J. (1996). Preparation and Characterization of Chitosan Microspheres as Drug Carrier for Prednisolone Sodium Phosphate as Model for Anti-Inflammatory Drugs, J. Controlled Release , 39: 17-25.
12.
Bayomi, M.A. , Al-Suwayeh, S.A., El-Helw, A.M., and Mesnad, A.F. (1998). Preparation of Casein-Chitosan Microspheres Containing Diltiazem Hydrochloride by an Aqueous Coacervation Technique, Pharm. Acta. Helvetiae., 73: 187-192.
13.
Vandenberg, G.W. , Drolet, C., Scott, S.L. and de la Noue , J. (2001). Factors Affecting Protein Release From Alginate-Chitosan Coacervate Microcapsules During Production and Gastric/Intestinal Simulation, J. Controlled Release, 77: 297-307.
14.
Liu, H., Fan, H., Cui, Y., Chen, Y., Yao, K. and Goh, J.C.H. ( 2007). Effects of the Controlled-Released Basic Fibroblast Growth Factor From ChitosanGelatin Microspheres on Human Fibroblasts Cultured on a ChitosanGelatin Scaffold, Biomacromolecules, 8: 1446-1455.
15.
Chiono, V., Pulieri, E., Vozzi, G., Ciardelli, G., Ahluwalia, A. and Giusti, P. ( 2008). Genipin-Crosslinked Chitosan/Gelatin Blends for Biomedical Applications, J. Mater. Sci: Mater. Med., 19: 889-898.
16.
Lim, S.T. , Martin, G.P., Berry, D.J. and Brown, M.B. (2000). Preparation and Evaluation of the In Vitro Drug Release Properties and Mucoadhesion of Novel Microspheres of Hyaluronic Acid and Chitosan, J. Controlled Release, 66: 281-292.
17.
Shu, X.Z. and Zhu, K.S. (2001). Chitosan/Gelatin Microspheres Prepared by Modified Emulsification and Ionotropic Gelation, J. Microencapsul., 18: 237-245.
18.
Zecchi, V., Aiedeh, K. and Orienti, I. ( 1997). In: Muzarelli, R.A.A. and Peter, M.G. (eds), Chitin Handbook, Grottammare: European Chitin Society, Grottammare. pp. 397.
19.
Silva, R., Boldt, S., Costa, V.M., Carmo, H., Carvalho, M., Carvalho, F. et al. (2007). Evaluation of GSH Adducts of Adrenaline in Biological Samples, Biomed. Chromatogr., 21: 670-679.
20.
Danila, G. ( 1984). Ghid de date toxicologice, Editura. Medicală., Bucureşti..
21.
Diebold, Y. , Jarrin, M., Saez, V., Carvahlo, E., Orea, M., Calonge, M. et al. (2007). Ocular Drug Delivery by Liposome - Chitosan Nanoparticle Complexes (LCS-NP), Biomaterials , 28: 1553-1564.
22.
Wang, L.Y., Gu, Y.H., Zhou, Q.Z., Ma, G.H., Wan, Y.H. and Su Z.G. ( 2006). Preparation and Characterization of Uniform-Sized Chitosan Microspheres Containing Insulin by Membrane Emulsification and a Two-Step Solidification Process, Colloids Surf., B, 50: 126-135.
23.
Yao, K. , Xu, M.X., Yin, Y.J., Zhao, J.Y. and Chen, X.L. (1996). pH-Sensitive Chitosan/Gelatin Hybrid Polymer Network Microspheres for Delivery of Cimetidine, Polym. Int., 39: 333-337.
24.
Shu, X.Z. and Zhu, K.J. (2002). Controlled Drug Release Properties of Ionically Cross-Linked Chitosan Beads: The Influence of Anion Structure, Int. J. Pharm., 233: 217-225.
25.
Kim, J.C. , Lee, H.Y., Kim, M.H., Lee, H.J., Kang, H.Y. and Kim, S.M. (2006). Preparation and Characterization of Chitosan/Gelatin Microcapsules Containing Triclosan, Colloids Surf, B, 52: 52-56.
