Microspheres mucoadhesive polymers

The benzyl ester of hyaluronic acid (HYAFF 11) is a highly mucoadhesive polymer which can be processed into microspheres. Such microspheres containing salmon calcitonin were intravaginally administered to rats as a dosage form for the prevention of ovariectomy osteopenia [65]. In recent studies, HYAFF 11-salmon calcitonin microspheres were formulated as single-dose pessaries, resulting in sustained plasma concentrations of calcitonin [67]. 

Genta, I., Costantini, M., Asti, A., Conti, B., and Montanari, L. (1998), Influence of glu-taraldehyde on drug release and mucoadhesive properties of chitosan microspheres, Carbohydr. Polym., 36,81-88. 

It is generally believed that microspheres that adhere to the nasal mucus elicit better immune response, and for this reason, many microspheres made of mucoadhesive polymers, such as chitosan, have been used extensively in the preparation of nasal vaccine formulations. 

Bioadhesive formulations and microsphere delivery systems in particular have attracted much attention. As drug formulations are usually rapidly removed from the site of deposition by the mucociliary clearance, increasing the retention time of drug in the nasal cavity via bioadhesion can increase bioavailability [28], Bioadhesion may be defined as the ability of a material (synthetic or biological) to adhere to a biological tissue for an extended period of time. When applied to a mucous membrane, a bioadhesive polymer may adhere primarily to the mucus layer or epithelial cell surface in a phenomenon known as mucoadhesion [29,30]. The bioadhesive properties of a wide range of materials have been evaluated over the last decade. 

Besides the polymer derivatization, combining the polymers in microsphere preparations can result in improved drug delivery and absorption characteristics. Hyaluronic acid-chitosan microspheres appeared to improve the absorption of incorporated gentamicin compared to the individual polymers, assembling the mucoadhesive potential of both polymers and the penetration-enhancing effect of chitosan [51,52],... 

Mikos and Peppas described the flow channel to measure the bioadhesion of polymer microparticles on mucin gels. Later Lehr et al. ° used an in situ loop model in the rat for the investigation of mucoadhesive microspheres (Fig. 3). They concluded that this approach allowed the study of the transit of particles. Another technique to study the mucoadhesive properties of microspheres is the electrobalance method, as... 

Nakamura et al. ° studied the adhesion of water-soluble and neutral polymers, hydroxypropyl cellulose (HPC), xanthan gum (XG), tamarind gum (TG), and polyvinyl alcohol (PVA) to nasal mucosa in vitro and in vivo. The polymers, mixed with a dye, were applied as powders to the nasal cavity of rabbits, and the remaining dye residue was determined at 2, 4, and 6 h after nasal instillation with a thin fiberscope. The polymer XG showed the longest residence time of the dye in the cavity, followed by TG, HPC, and PVA in decreasing order. For the mixture XG and XG-PVA (2 8), some residue of dye could still be observed 6h after administration. The order of adhesion of these polymers to agar plates in vitro agreed with that of their mucoadhesion in vivo. Ilium et al. introduced bioadhesive microspheres for nasal delivery of poorly absorbable drugs. Radiolabelled microspheres made from diethylaminoethyl (DEAE)-dextran, starch microspheres, and albumin microspheres were administered to human volunteers and appeared to be cleared significantly slower than solutions or... 

In spite of these formidable challenges, the attractiveness of oral route has fueled the exploration of an incredibly diverse set of strategies to deliver proteins and peptides and the subject has been exhaustively reviewed. The various approaches include permeation enhancers, enzyme inhibitors, mucoadhesives, multifunctional matrices that simultaneously incorporate the above strategies, enteric coatings that offer protection from the acidic environment of the stomach, encapsulation (liposomes, microspheres, and nanoparticles), pH-sensitive polymers, microemulsions, carriers (delivery agents), and protein modification either to simply enhance permeability or to exploit specific transporters. While proof-of-concept has been demonstrated with most of these delivery systems in animal... 

Albertini, B., Passerini, N., Sabatino, M., Di Franco, P, Vitali, B., Brigidi, P., and L. Rodriguez. Polymer-lipid based mucoadhesive microspheres prepared by spray-congealing for the vaginal delivery of econazole nitrate. Eur J Pharm Sci, 36 (2009) 591-601. 

---