Bioadhesives vaginal delivery systems

Richardson, J.L., and Armstrong, T.I., Vaginal Delivery of Calcitonin by Hyaluronic Acid Formulations. In Bioadhesive Drug Delivery Systems (E. Mathiowitz, D.E. Chickering, III, and C.-M. Lehr, eds.), Marcel Dekker, Inc., New York, 1999, pp. 563-599. 

In recent years, efforts have been made to find methods to increase peptide and protein absorption via the vaginal mucosa by the use of penetration enhancers, enzyme inhibitors, and bioadhesive drug delivery systems. 

Richardson, J. L., Farraj, N. F., and Ilium, L. (1992), Enhanced vaginal absorption of insulin in sheep using lysophosphatidylcholine and a bioadhesive microsphere delivery system, Int. J. Pharm., 88, 319-325. 

A host of bioadhesive controlled release systems have been proposed in recent years. Among the most commonly studied applications of bioadhesive materials is the area of buccal controlled delivery [408], The buccal delivery of small peptides from bioadhesive polymers was studied by Bodde and coworkers [409], and a wide range of compositions based on poly(butyl acrylate) and/or poly(acrylic acid) gave satisfactory performance. Bioadhesive poly(acrylic add)-based formulations have also been used for oral applications [402,410] for the sustained delivery of chlorothiazide [410] and for a thin bioadhesive patch for treatment of gingivitis and periodontal disease [411]. Other bioadhesive applications of polyelectrolytes include materials for ophthalmic vehicles [412,413], and systems for oral [410,414,415-419], rectal [420,421] vaginal [422] and nasal [423] drug delivery. 

The bioadhesive properties of hydrophobic polybasic gels containing ACV-dimethylami-noethyl methacrylate-co-methyl methacrylate were investigated in view of their use as vaginal drug delivery systems [72]. The bioadhesive properties of such gels make them suitable for site-specific and pH-controlled drug delivery. 

Spermicide-antiviral the polymer appears to be an effective delivery system for the spermicidal/antiviral agent nonoxynol-9. By its ability to adhere to vaginal tissue while retaining nonoxynol-9 in its gel structure, it is an excellent extended effect spermicide. As an antiviral, nonoxynol-9 can only kill free HIV and is not noticeably active when the virus is within a lymphocyte. In contrast, the bioadhesive gel containing nonoxynol-9 attaches to lymphocytes and maintains sufficient contact time to allow the nonoxynol-9 surfactant to disrupt the cell wall, thus eliminating the lymphocyte and killing the vims within. This suggests that the polymer may be useful in the prophylaxis of AIDS and the treatment of other sexually transmitted diseases. 

Kast, C. E., Valenta, C., Leopold, M., and Bernkop-Schnurch, A. (2002), Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole, J. Controlled Release, 81,347-354. 

Xanthan gum can be used to increase the bioadhesive strength in vaginal formulations and as a binder in colon specific drug delivery systems. ... 

Mucoadhesive drug delivery systems are comprised of administration of drug across the mucosal membrane using a mucoadhesive/bioadhesive polymer through various noninvasive routes such as peroral, ocular, buccal, nasal, stomach, intestinal, colon, vaginal, rectal, cervical or vulval. The drug delivery systems, which have made use of chitosan as a carrier for administration through various routes, have been represented in Table 2.2. 

The key objective of our efforts has been to develop a vaginal formulation that optimizes spermicidal and antiviral activity while enhancing spreading and true bioadhesiveness. Utilization of strict design principles for an excipient delivery vehicle, which included substantivity to vaginal mucosa, saline compatibility, compatibility with a wide range of spermicidal and antiviral compounds, low irritation potential, sperm impedance, system stability, and efficacy after stressed storage conditions, resulted in the development of DCE s [11,12,13]. Based on the results from in vitro studies, the DCE vehicle was selected for clinical development. 

Site-specific delivery will require the use of a self-locating system, typically a bioadhesive formulation, although an IVR, due to its elastomeric nature, will remain located high in the vaginal space. Conversely, for rapid distribution throughout the space, semisolid or fast-dissolving solid systems will be required. For semisolids, flow properties and viscoelastic character will be the critical determinants of their ability to spread rapidly from their point of application. 

---