Thermosetting gel for the delivery of 5-aminolevulinic acid esters to the cervix

Autor: Sabine Collaud, Qian Peng, Norbert Lange, Robert Gurny
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Pathology
medicine.medical_specialty
Porphyrins
Skin/drug effects/metabolism
Drug Carriers/*chemistry
Mice
Nude
Uterine Cervical Neoplasms
Pharmaceutical Science
Excipient
Context (language use)
Cervix Uteri
In Vitro Techniques
Pharmacology
Administration
Cutaneous
Dosage form
Phase Transition
Cervix Uteri/*metabolism
Mice
In vivo
Medicine
Animals
Uterine Cervical Neoplasms/drug therapy
Skin
Drug Carriers
ddc:615
Photosensitizing Agents
business.industry
Photochemotherapy/methods
Administration Cutaneous
Temperature
Hydrogels
Aminolevulinic Acid
Poloxamer
Photosensitizing Agents/*administration & dosage/chemistry/pharmacokinetics/therapeutic use
Aminolevulinic Acid/*administration & dosage/chemistry/pharmacokinetics/therapeutic use
Hydrogels/*chemistry
Bioavailability
Mice Nude
Photochemotherapy
Solubility
Self-healing hydrogels
Poloxamer 407
Female
Porphyrins/biosynthesis/blood/cerebrospinal fluid
business
medicine.drug
Zdroj: Journal of Pharmaceutical Sciences, Vol. 97, No 7 (2008) pp. 2680-90
ISSN: 0022-3549
Popis: 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.
Databáze: OpenAIRE
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