Transdermal delivery of selegiline from alginate–Pluronic composite thermogels

• Published in: International journal of pharmaceutics Vol. 415; no. 1; pp. 119 - 128
• Main Authors: Chen, Chih-Chieh, Fang, Chia-Lang, Al-Suwayeh, Saleh A., Leu, Yann-Lii, Fang, Jia-You
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30.08.2011; Elsevier
• Subjects: Administration, Cutaneous; Alginate; Alginates - chemistry; Animals; Biological and medical sciences; Chromatography, High Pressure Liquid; composite polymers; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Compounding; Female; Freeze Drying; gelatinization temperature; gels; General pharmacology; Glucuronic Acid - chemistry; Hexuronic Acids - chemistry; hydrocolloids; Hydrogels; In Vitro Techniques; Medical sciences; Mice; Mice, Nude; Microscopy, Electron, Scanning; Monoamine Oxidase Inhibitors - administration & dosage; Monoamine Oxidase Inhibitors - chemistry; Monoamine Oxidase Inhibitors - pharmacokinetics; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phase Transition; Pluronic F127; Poloxamer - chemistry; porosity; scanning electron microscopy; Selegiline; Selegiline - administration & dosage; Selegiline - chemistry; Selegiline - pharmacokinetics; Skin - metabolism; Skin Absorption; Skin Temperature; Surface Properties; Swine; Thermogel; Transdermal delivery; Transition Temperature; Selegiline; Transdermal delivery; Pluronic F127; Alginate; Thermogel; Monoamine oxidase B inhibitor; Vehicle(excipient); Uronide polymer; Laxative; Composite material; Percutaneous route; Cyclic ether copolymer; Propylene oxide copolymer; Pharmaceutical technology; Enzyme; Enzyme inhibitor; Alginates; Ethylene oxide copolymer; Antiparkinson agent; Amine oxidase (flavin-containing); Polyelectrolyte; Triblock copolymer; Poloxamer; Oside polymer; Oxidoreductases
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.05.060

Representative visual inspection of the aqueous copolymer system at 15 °C (A), 20 °C (B), 25 °C (C), 30 °C (D), and 35 °C (E) (left to right: PF127 (20%), alginate and PF127 blending (A + P, 20% + 0.63%), and the alginate–Pluronic F127 composite copolymer (AP, 15%)). The present work was carried out to design a practical, controlled-release transdermal system for selegiline using thermosensitive hydrogels. The copolymers of alginate and Pluronic F127 (PF127) were used to design thermogels by either physical blending (A + P) or chemical grafting (AP). The thermogels were characterized in terms of the sol–gel temperature, scanning electron microscopy (SEM), degradation ratio, and skin permeation behavior. The chemical grafting of alginate to PF127 could delay the sol–gel temperature from 24.1 to 30.4 °C, which is near the temperature of the skin surface. The gelling temperature of the physical mixture of alginate and PF127 (A + P) did not significantly differ. The porosity of the A + P structure was greater compared to that of the AP structure. AP thermogels were regularly degraded, with 60% of the gel matrix remaining after a 48-h incubation. PF127 and A + P hydrogels showed almost no degradation. The results of skin permeation across porcine skin and nude mouse skin suggested that the thermogels could produce sustained selegiline release, with AP showing the most-sustained permeation. AP hydrogels exhibited linear permeation properties for the transdermal delivery of selegiline. Inter-subject variations in skin permeation were reduced by incorporation of the thermogel. Such a thermosensitive hydrogel can be advantageous as a topical therapeutic formulation for selegiline.