Design, evaluation and in vivo pharmacokinetic study of a cationic flexible liposomes for enhanced transdermal delivery of pramipexole

Pramipexole is a widely preferred antiparkinsonian agent because of its several advantages, one being the delayed onset of motor fluctuations and dyskinesia observed with other antiparkinsonian drugs. However, it may cause pulsatile stimulation of the dopamine receptors responsible for the majority of the side effects such as orthostatic hypotension, constipation, dizziness, drowsiness, dry mouth, etc. Thus, the objective of the present work was to develop flexible liposomes of pramipexole for enhanced transdermal drug delivery and consequently to reduce side effects. Structure of phospholipids, edge activator, and surfactants being major determinants of liposomes, phospholipids of varying hydrocarbon chain length and degree of substitution, and cationic and anionic surfactants (sodium hexadecyl sulfate or cetylpyridinium chloride) were used for formulating flexible liposomes. All the batches of flexible liposomes of pramipexole were prepared by the thin-film hydration method. Liposomes were characterized by TEM, % drug entrapment, vesicle size, and deformability index. Liposomes were incorporated into the gel base and formulated as a transdermal patch. Ex-vivo drug release studies demonstrated greater and faster drug releases from all the prepared cationic flexible liposomal (CFL) gel patches as compared to flexible and anionic flexible liposomal gel patches. Further, the flexible liposomes of shorter carbon chain length and monosubstitution provide rapid drug release, while the sustained release was observed through liposomes comprising of longer carbon chain length and increased substitution. Pharmacokinetic studies demonstrated that the designed transdermal patches were capable of delivering pramipexole at the desired concentration and overcome the skin barrier function efficiently. Hence, CFL transdermal patch prepared with phospholipids containing higher carbon content appears to be promising to deliver pramipexole by the transdermal route and can thus overcome the pulsatile stimulation of dopamine receptors and associated side effects.

Automated summary

The study aimed to develop flexible liposomes of pramipexole for enhanced transdermal drug delivery and reduced side effects. Results showed greater and faster drug release in cationic flexible liposomal gel patches, with shorter carbon chain length and mono-substitution providing rapid drug release.