Lamellar Liquid Crystalline Phases for Cutaneous Delivery of Paclitaxel: Impact of the Monoglyceride

• Published in: Pharmaceutical research 2013-03, Vol.30 (3), p.694-706
• Main Authors: Hosmer, Jaclyn M., Steiner, Alexandre A., Lopes, Luciana B.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - pharmacokinetics; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Caprylates - chemistry; Caprylates - metabolism; Chemotherapy; Drug Carriers - chemistry; Drug Carriers - metabolism; General pharmacology; Glycerides - chemistry; Glycerides - metabolism; Liquid Crystals - chemistry; Male; Medical Law; Medical sciences; Monoglycerides - chemistry; Monoglycerides - metabolism; Paclitaxel - administration & dosage; Paclitaxel - pharmacokinetics; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Phase Transition; Rats; Research Paper; Skin - drug effects; Skin - metabolism; Skin - ultrastructure; Skin Absorption - drug effects; Skin Irritancy Tests; Swine; Transdermal medication
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-012-0908-0

Purpose To develop liquid crystalline phases with monoglycerides, and assess whether the monoglyceride type favors cutaneous over transdermal paclitaxel delivery. Methods BRIJ-based lamellar phases were prepared with 0.5% paclitaxel and 20% of either monocaprylin (LP-MC), monomyristolein (LP-MM) or monoolein (LP-MO). Skin electrical resistance, drug release and cutaneous delivery in vitro and in vivo were assessed. Viability of skin equivalents and release of IL-1α were assessed as indexes of irritation potential. Results An inverse relationship between monoglyceride acyl chain length and amount of paclitaxel delivered was observed. Although the largest paclitaxel amounts were delivered by LP-MC, all formulations delivered higher levels of drug in the skin (56–64-fold) than across the tissue. The superiority of LP-MC seems related to a stronger decrease in skin resistance (as an index of permeability), and not to increased drug release. LP-MC displayed similar penetration-enhancing ability in vivo, and a much lower irritation potential than Triton-X100 (a moderate irritant), leading to 3-fold higher skin equivalent viability and release of 60-fold less IL-1α. Conclusions Even though LP-MC delivered the largest amounts of paclitaxel, all formulations provided similar cutaneous/transdermal delivery ratios, suggesting that changing the monoglyceride acyl chain length did not affect the balance between cutaneous and transdermal delivery.