pH-responsive drug release from functionalized electrospun poly(caprolactone) scaffolds under simulatedin vivoenvironment

Abstract

The difference in the tumor environment from the normal healthy tissue can be therapeutically exploited to develop new strategies for controlled and site-specific drug delivery. In the present study, a continuous flow system is designed to represent the in vivo environment of a tumor tissue and drug release is studied at different pH that represents normal tissue pH, tumor tissue pH, and stomach pH. The results obtained from these experiments were translated to a human embryonic kidney cell culture system and the effect of drug released from these functionalized PCL scaffolds on cell viability was studied. A significant decrease in cell viability was observed with the doxorubicin hydrochloride concentration that would be released at acidic pH, either present as a result of tumor extracellular environment or could be achieved via fabrication of a composite scaffold with a polyvinyl alcohol hydrogel containing acid. In the end, a study using zebrafish as an animal model is also undertaken in order to study the drug release from the scaffolds in vivo.

Maleimide functionalized polycaprolactone micelles for glutathione quenching and doxorubicin delivery

“…40 Interestingly, polymeric micelles from aliphatic polyester such as PCL are reported to be pH-responsive and can be tailored to achieve pH-dependent drug release. 61,98,99 To analyze the possibility of using PMCL as a drug carrier capable of accumulating at the tumor site through an EPR effect due to the smaller micelles size and releasing a larger amount of the loaded drug as a result of the low pH, DOX was loaded since this anticancer drug is FDA approved for a wide spectrum of tumors. 100 DOX was encapsulated into the hydrophobic core of the micelles using the solvent evaporation method and dialyzed as described above.…”

pH-Responsive Electrospun Nanofibers and Their Applications

“…Jassal et al used a sodium hydroxide (NaOH) solution to introduce carboxylic acid groups on a PCL scaffold. [146] An 8 h treatment prevented the breakage of e-spun nanofibers while surface degradation occurred after 24 h including hydrolysis of the PCL membranes. DOX was then grafted to the surface by immersing the mesh in a DOX solution.…”

“…PDA adheres to all types of surfaces due to the presence of catechol moieties and amino groups, which react with nucleophiles and electrophiles. [154] J. Jiang et al reported a mussel inspired system [144] Surface polymerization PCL Polydopamine (PDA) [70,145] Surface hydrolyzation PCL Functional groups (-COOH) / Doxorubicin (DOX) [146] Surface deposition PI Silica nanoparticles/ Decanoic acid-TiO 2 DA-TiO 2 [147] PA6 Polyaniline (PA) [148] based on poly(e-caprolactone) (PCL) nanofibers coated with PDA. [70,145] Therefore, by functionalizing the PCL nanofibers with plasma treatment, functional groups (-CO-, -COOH-) were deposited on the surface of e-spun nanofibers.…”

Electrospun Nanofibers: Recent Applications in Drug Delivery and Cancer Therapy

“…These NFs not only showed good biocompatibility in fibroblasts (L929), they were also able to stimulate cell growth compared to untreated cells. Functionalized electrospun PCL scaffolds sensitive to pH changes, were loaded with DOX and tested at different pH levels (from 7.4 to 2.5) finding the highest drug release (90%–95%) at the lowest pH levels [61]. This was observed in the human embryonic kidney cells (HEK) treated with these scaffolds with a cell viability at pH 6 lower than those obtained at pH 7.2.…”