Design and Characterization of Cyclosporine A-Loaded Nanofibers for Enhanced Drug Dissolution

Abstract

Despite widespread use as an immunosuppressant, the therapeutic efficacy of the undecapeptide cyclosporine A (CyA) is compromised when given by the oral route because of the innate hydrophobicity of the drug molecule, potentially leading to poor aqueous solubility and bioavailability. The aim of this study was to develop and characterize nanofibers based on the water-miscible polymer polyvinylpyrrolidone (PVP), incorporating CyA preloaded into polymeric surfactants so as to promote micelle formation on hydration; therefore, this approach represents the novel combination of three dissolution enhancement methodologies, namely solid dispersion technology, micellar systems, and nanofibers with enhanced surface area. The preparation of the nanofibers was performed in two steps. First, mixed micelles composed of the water-soluble vitamin E derivative D-α-tocopheryl poly(ethylene glycol) 1000 succinate and the amphiphilic triblock polymer Pluronic F127 (Poloxamer 407) were prepared. The micelles were characterized in terms of size, surface charge, drug loading, and encapsulation efficiency using transmission electron microscopy, dynamic light scattering, Fourier-transform infrared spectroscopy, high-performance liquid chromatography, and scanning electron and atomic force microscopy analysis. Nanofibers composed of PVP and the drugloaded surfactant system were then prepared via electrospinning, with accompanying thermal, spectroscopic, and surface topological analysis. Dissolution studies indicated an extremely rapid dissolution profile for the fibers compared to the drug alone, while wettability studies also indicated a marked decrease in contact angle compared to the drug alone. Overall, the new approach appears to offer a viable means for considerably improving the dissolution of the hydrophobic peptide CyA, with associated implications for improved oral bioavailability.

Electrospun PVP-Core/PHBV-Shell Fibers to Eliminate Tailing Off for an Improved Sustained Release of Curcumin

“…As a “brother” technology of electrospraying, electrospinning uses electrostatic field forces to fabricate continuous micro-/nanofibers. − In recent years, coaxial electrospinning, an “improved version” of traditional single-fluid electrospinning, has been developed and widely used in the preparation of functional materials. − The encapsulation efficiency and release characteristics of the drug will be improved when they attach to the surface of the carrier or are encapsulated inside. − Inspired by this concept, a series of drug-sustained release strategies have been realized by electrospinning medicine nanofibers …”

Designing a Prolonged Method of Therapeutic Delivery to Support Rehabilitation From Ototoxic Damage in a Schwann Cell Model

“…However, its pharmacokinetic properties provide some unique challenges in its bioavailability. It has very low water solubility, making it difficult to encapsulate into a microparticle at a reasonable yield (43,45). In addition, cyclosporine has poor membrane permeability, making it a less ideal candidate for a therapeutic agent of interest to permeate across the round window membrane (45).…”

Cyclosporine A Delivery Platform for Veterinary Ophthalmology—A New Concept for Advanced Ophthalmology

“…Poor membrane permeation after topical application, especially with oral administration, related to low water solubility linked with high lipophilic characteristics (log P = 2.92 at pH 7.4), and significant rigidity of the cyclic structure of the CsA results in a limited absorption of the peptide across the gastrointestinal membrane. For that reason, Cyclosporine A (CsA) was classified as a Class IV under the biopharmaceutics classification system [ 18 , 19 ]. Therefore, the proper selection of drug administration is essential for successful therapy.…”

“…It has been demonstrated that any mutation that blocks JNK and p38 signaling pathways revokes the NF-AT cis-element transcription activation which has binding sites for NFAT family members and Activator protein 1 (AP-1), and both are involved in IL-2 expression [ 26 ]. Moreover, the inhibition of both JNK and p38 signaling pathways is related to the upstream level of MAPKK-K activation for example, the MEKK1/MAPKK-Ks participates in the JNK and p38 signaling pathways through MKK7 and MKK6 [ 18 ]. Other potential indirect actions of CsA suggested that the JNK and p38 signaling pathways inhibition could be related to over-expression of Vav1/Vav2/Dbl and GEF for Rac1 or Cdc42.…”