Poloxamer188 composite electrospun poly L-lactic acid fibrous nonwoven: Sustained in vitro and in vivo release letrozole as a subcutaneous implant

Abstract

Poloxamer188 composite poly L-lactic acid (PLLA) electrospun fibrous nonwovens (EFNW) were prepared by simple letrozole-poloxamer188-PLLA co-solution electrospinning and used as subcutaneous implants to sustained release letrozole. Contents of poloxamer188 and letrozole were varied to investigate the effect of the two compounds’ amounts on drug release behavior. Materials’ combination and drug incorporation in fibers were investigated by X-ray diffraction and differential thermal calorimetry. Letrozole contents in vitro and in vivo were all determined by high-performance liquid chromatography-ultraviolet spectrometry. Meanwhile, in order to analyze the mechanism of drug release behavior and show modulated drug release by electrospun fibers, letrozole-poloxamer188 solid dispersions (SDs) and letrozole-poloxamer188poly L-lactic acid-dichloromethane solution cast films (CFs) were also studied. Plasma letrozole concentration curves of subcutaneous implanting EFNW and daily oral administration of poloxamer188-letrozole SD on female rabbits were investigated and compared. Fibers of desirable morphology were obtained. During the whole release process of all EFNWs, water-insoluble letrozole could be released in the form of being dissolved. Letrozole release rates increased with increasing poloxamer188 content and decreased with increasing letrozole content. When letrozole and poloxamer188 content in fibers was 30% and 150% (EFNW-30-150%), respectively (with respect to PLLA in mass ratio), the release curve presented a desirable profile. After subcutaneous implant of EFNW-30-150%, the plasma concentration curve presented a later peak time and lower maximum value, and a comparable bioavailability with daily oral administration of poloxamer188-letrozole SD solution within 15 days. The research provided primary and encouraging information to use EFNW as a novel subcutaneous implant for sustained delivery of water-insoluble drugs.