Functionalized Hydrophobic Poly(glycerol-co-ε-caprolactone) Depots for Controlled Drug Release

Abstract

A limitation to many polymer-based drug delivery systems is the ability to customize a particular polymer composition for tailoring drug release kinetics to a specific clinical application. In this study, we investigated the structure-function effects of conjugating various hydrophobic biocompatible side chains to poly(glycerol-co-caprolactone) copolymers with the goal of achieving prolonged and controlled release of a chemotherapeutic agent. The choice of side chain significantly affected the resulting polymer properties including thermal transitions, relative crystallinity (ΔHf), and hydrophobicity. Drug-loaded films cast from solutions of polymer and 10-hydroxycamptothecin demonstrated prolonged release from four to over seven weeks depending upon side chain structure without initial burst release behavior. Use of the stearic acid-conjugated poly(glycerol-co-caprolactone) films afforded substantial anti-cancer activity in vitro for at least 50 days when exposed to fresh cultures of A549 human lung cancer cells over 24-hour intervals, correlating well with the measured drug release kinetics.

3D superhydrophobic electrospun meshes as reinforcement materials for sustained local drug delivery against colorectal cancer cells

“…The superhydrophobic meshes under investigation are electrospun poly(ε-caprolactone) (PCL) doped with 10% poly(glycerol monostearate-co-ε-caprolactone) (PGC-C18) (Figure 2A). PGC-C18 was selected as the polymer dopant due to the relative ease in functionalizing the backbone with many pendant groups, including stearic acid [21, 27, 31], where the addition of 10% PGC-C18 produces the desired superhydrophobic effect due to a high apparent contact angle (143°) (Table 1). PCL was purchased, whereas PGC-C18 was synthesized as shown in Figure 2A.…”

“…PCL was purchased, whereas PGC-C18 was synthesized as shown in Figure 2A. [21, 27, 31] Briefly, the carbonate monomer of glycerol, 5-benzyloxy-1,3-dioxan-2-one, was synthesized, after which ε-caprolactone and the carbonate monomer were copolymerized in a 4:1 ratio (21 kD). The benzyl group on the secondary hydroxyl of the carbonate monomer of the copolymer was subsequently removed, followed by the addition of stearic acid using a standard DCC coupling method.…”

Titanium wire implants with nanotube arrays: A study model for localized cancer treatment

“…A foreign-body response may result in a collagenous fibrous capsule developing around the implant, thus preventing adequate diffusion of the drug into the tissue. Further understanding of the interplay between localized delivery and tissue healing after implant insertion to prevent this response from occurring is crucial for the future application of such devices into real systems [66,67].…”

Synthetic Biomaterials from Metabolically Derived Synthons

“…Subsequent coupling of various fatty acids of chain lengths C8, C12, C14, C16, and C18 to the secondary hydroxyl afforded polymers with different degrees of hydrophobicity, crystallinity, and film forming capacity. 200 Encapsulation of chemotherapeutic agents [e.g., 10-hydroxycamptothecin (10HCPT) or paclitaxel (Pax)] into cast films of the polymer results in drug release rates dependent on the fatty acid chain length with extended, prolonged release of the agent occurring over 7 weeks for the most hydrophobic film, the C18 analog. Repeated exposure of the 10HCPTloaded or paclitaxel-loaded polymer films to fresh lung cancer cells in vitro afforded cell death for over 50 days.…”