Mucoadhesive Polymer Hyaluronan as Biodegradable Cationic/Zwitterionic-Drug Delivery Vehicle

Mucoadhesive polymers in pharmaceutical formulations release drugs in mucosal areas. They interact and fix to mucus through molecular interpenetration, etc., which increase drug bioavailability. Polymers physicochemical properties affect formulation mucoadhesion, rheological behaviour and drug absorption. Hyaluronan (HA) is selected as a mucoadhesive and biodegradable polymer. Geometric, topological and fractal analyses are carried out with program TOPO. Reference calculations are performed with algorithm GEPOL. Procedure TOPO underestimates molecular volume by 0.7 %. The error results 5 % in surface area and derived topological indices. The solvent-accessible surface is undercalculated by 3 %: from hexamer HA to HA·3Ca and hydrate, the hydrophobic term rises by 42% and decays by 26 %, as well as the hydrophilic part drops by 14% and rises by 58 %, in agreement with the number of H-bonds. The accessibility rises by 9 % and decays by 8 %. The fractal dimension is underevaluated by 1 % and, for HA, it results 1.566; on going to HA·3Ca and hydrate, it rises by 2 % and 1 %. The nonburied-atoms dimension increases by 11 %: for HA, it results 1.725. When going to HA·3Ca and hydrate, it augments by 4 % and 0.3%. Ongoing from HA to HA·3Ca and hydrate, the external minus molecular dimension enlarges by 20 % and decays by 9 %. The hydrate globularity is lower than for water, Ca 2+ and averages of O-atoms in HA. The rugosity of Ca 2+ is smaller than for hydrate, averages of O-atoms in HA and water. The accessibilities of Ca 2+ and water are greater than for hydrate. As cations exchange in HA·3Ca requires Ca 2+ alteration, rises of drug zwitterionic character and acidic pH increase absorption.