title: Thermosetting gel for the delivery of 5-aminolevulinic acid esters to the cervix.
abstract: 5-Aminolevulinic acid (5-ALA)-mediated photodynamic therapy has been proposed as an alternative, cervix-sparing treatment for cervical intraepithelial neoplasia (CIN). In this context, topical application of 5-ALA to the cervix is beneficial due to the small necessary dose and its minimal side effects. Therefore, lipophilic 5-ALA esters, such as hexylaminolevulinate (HAL), have led to improved local bioavailability and therapeutic efficacy. Hydrogels have shown to be more appropriate for the local delivery of these derivatives, but due to the limited long-term stability of such formulations at 25 degrees C, the development of an extemporaneously prepared hydrogel targeting CIN can be advantageous. Therefore, a poloxamer 407 thermosetting gel, which is liquid at room temperature and becomes a semi-solid when in contact with the female genital tract, has been evaluated in vitro and in vivo. Rheological evaluation has shown that a 17.0% poloxamer 407 hydrogel with a sol-gel transition at 24.8 +/- 0.6 degrees C was the best formulation for easy application and optimal residence time. Furthermore, similarly to other hydrogels previously tested, such a formulation shows a more complete HAL release in vitro than conventional cream vehicles, and tends to increase porphyrin accumulation in nude mice skin. Finally, in vitro release profiles were correlated to the in vivo results.
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, 1211 Geneva 4, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Collaud
authors.forename: Qian
authors.initials: Q
authors.lastname: Peng
authors.forename: Robert
authors.initials: R
authors.lastname: Gurny
authors.forename: Norbert
authors.initials: N
authors.lastname: Lange
mesh_terms: D000279:Administration, Cutaneous; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D002584:Cervix Uteri / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D020100:Hydrogels / Q000737:chemistry*; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D044367:Phase Transition; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D011166:Porphyrins / Q000096:biosynthesis / Q000097:blood / Q000134:cerebrospinal fluid; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012995:Solubility; D013696:Temperature; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy