Polymer coated mucoadhesive liposomes intended for the management of xerostomia.

The aim of this work was to prepare and test different pharmaceutical formulations in respect of their potential in relieving dry mouth symptom. Since many of the products available on the market provide only temporary relief to the patients, there is need for new formulations able to retain on the oral mucosa. The prolonged moisture protection could be achieved by combining mucoadhesive materials, such as polymers containing hydrogen bonding groups, with vesicles capable of releasing hydration medium from the inner compartment. In this study three different types of liposomes (positively, negatively and neutrally charged) were coated with five different types of polymers: low-methoxylated pectin (LM-pectin), high-methoxylated pectin (HM-pectin), alginate, chitosan and hydrophobically modified ethyl hydroxyethyl cellulose (HM-EHEC). The particle size and the zeta potential of the obtained carriers were tested by measuring dynamic light scattering (DLS) and electrophoretic mobility. Later on, selected positively charged liposomes were deposited on a negatively charged mica surface and depicted by atomic force microscopy (AFM). The water sorption properties of polymers, uncoated liposomes and polymer-coated liposomes were studied by the means of dynamic vapor sorption (DVS). The experiments were performed within the relative humidity range RH=95-0-95%, at 35°C. It was found that coating the liposomes with polymers significantly increased the water sorption capacity of the formulations, making them an attractive choice for hydration of the oral mucosa.

Water sorption properties of HM-pectin and liposomes intended to alleviate dry mouth.

Pharmaceutical formulations intended for treatment of xerostomia (dry mouth) should be able to keep the oral mucosa hydrated for a prolonged period of time. The products already existing on the market contain water-soluble polymers, however their ability to moisturize the oral mucosa for a longer period of time seems limited. In this paper the sorption properties of water vapor of high-methoxylated pectin (HM-pectin, a hydrophilic biopolymer) and phosphatidylcholine-based (Soya-PC) liposomes have been studied and compared using a gravimetric method. The kinetics of water desorption and sorption have been recorded over the relative humidity range RH=95-0-95%, at 35°C. The obtained isotherms were found to be well described by the n-layer Brunauer-Emmet-Teller (BET) adsorption model. The water isotherms on HM-pectin were Type II (IUPAC), while water isotherms on liposomes were Type III. The maximum water sorption capacity of liposomes (1.2mg water per mg of adsorbent at 95% RH) was found to be twice as high as for pectin. Due to the slower water release from the liposomes, as well as their high water sorption capacity, they seem to have great potential in relieving the symptoms of dry mouth syndrome.

An in vitro study of mucoadhesion and biocompatibility of polymer coated liposomes on HT29-MTX mucus-producing cells.

Drug delivery to the oral cavity poses a significant challenge due to the short residence time of the formulations at the site of action. From this point of view, nanoparticulate drug delivery systems with ability to adhere to the oral mucosa are advantageous as they could increase the effectiveness of the therapy. Positively, negatively and neutrally charged liposomes were coated with four different types of polymers: alginate, low-ester pectin, chitosan and hydrophobically modified ethyl hydroxyethyl cellulose. The mucoadhesion was studied using a novel in vitro method allowing the liposomes to interact with a mucus-producing confluent HT29-MTX cell-line without applying any external force. MTT viability and paracellular permeability tests were conducted on the same cell-line. The alginate-coated liposomes achieved a high specific (genuine) mucin interaction, with a low potential of cell-irritation. The positively charged uncoated liposomes achieved the highest initial mucoadhesion, but also displayed a higher probability of cell-irritation. The chitosan-coated liposomes displayed the highest potential for long lasting mucoadhesion, but with the drawback of a higher general adhesion (tack) and a higher potential for irritating the cells.