Evaluation of bioadhesive polymers as delivery systems for nose to brain delivery: in vitro characterisation studies.
There is an increasing need for nasal drug delivery systems that could improve the efficiency of the direct nose to brain pathway especially for drugs for treatment of central nervous system disorders. Novel approaches that are able to combine active targeting of a formulation to the olfactory region with controlled release bioadhesive characteristics, for maintaining the drug on the absorption site are suggested. If necessary an absorption enhancer could be incorporated. Low methylated pectins have been shown to gel and be retained in the nasal cavity after deposition. Chitosan is known to be bioadhesive and also to work as an absorption enhancer. Consequently, two types of pectins, LM-5 and LM-12, together with chitosan G210, were selected for characterisation in terms of molecular weight, gelling ability and viscosity. Furthermore, studies on the in vitro release of model drugs from candidate formulations and the transport of drugs across MDCK1 cell monolayers in the presence of pectin and chitosan were also performed. Bioadhesive formulations providing controlled release with increased or decreased epithelial transport were developed. Due to their promising characteristics 3% LM-5, 1% LM-12 pectin and 1% chitosan G210 formulations were selected for further biological evaluation in animal models.
Charlton
S T
ST
School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Davis
S S
SS
Illum
L
L
D000268:Adhesiveness; D000281:Administration, Intranasal; D000818:Animals; D001572:Benzofurans / Q000737:chemistry; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D003692:Delayed-Action Preparations; D004058:Diffusion; D004285:Dogs; D004337:Drug Carriers; D004339:Drug Compounding; D004847:Epithelial Cells / Q000378:metabolism*; D005782:Gels; D007700:Kinetics; D008353:Mannitol / Q000378:metabolism; D008745:Methylation; D008956:Models, Chemical; D008970:Molecular Weight; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism*; D010368:Pectins / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011433:Propranolol / Q000378:metabolism; D012995:Solubility; D014014:Tissue Adhesives / Q000737:chemistry*; D014783:Viscosity
D001572:Benzofurans; D002491:Central Nervous System Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D011108:Polymers; D014014:Tissue Adhesives; D008353:Mannitol; D010368:Pectins; D048271:Chitosan; D011433:Propranolol; C089586:saprisartan potassium