Drug-Induced Morphology Switch in Drug Delivery Systems Based on Poly(2-oxazoline)s

Abstract

Defined aggregates of polymers such as polymeric micelles are of great importance in the development of pharmaceutical formulations. The amount of drug that can be formulated by a drug delivery system is an important issue, and most drug delivery systems suffer from their relatively low drug-loading capacity. However, as the loading capacities increase, i.e., promoted by good drug–polymer interactions, the drug may affect the morphology and stability of the micellar system. We investigated this effect in a prominent system with very high capacity for hydrophobic drugs and found extraordinary stability as well as a profound morphology change upon incorporation of paclitaxel into micelles of amphiphilic ABA poly(2-oxazoline) triblock copolymers. The hydrophilic blocks A comprised poly(2-methyl-2-oxazoline), while the middle blocks B were either just barely hydrophobic poly(2-n-butyl-2-oxazoline) or highly hydrophobic poly(2-n-nonyl-2-oxazoline). The aggregation behavior of both polymers and their formulations with varying paclitaxel contents were investigated by means of dynamic light scattering, atomic force microscopy, (cryogenic) transmission electron microscopy, and small-angle neutron scattering. While without drug, wormlike micelles were present, after incorporation of small amounts of drugs only spherical morphologies remained. Furthermore, the much more hydrophobic poly(2-n-nonyl-2-oxazoline)-containing triblock copolymer exhibited only half the capacity for paclitaxel than the poly(2-n-butyl-2-oxazoline)-containing copolymer along with a lower stability. In the latter, contents of paclitaxel of 8 wt % or higher resulted in a raspberry-like micellar core.

Polymers and Nanomedicine: Considerations on Variability and Reproducibility When Combining Complex Systems

“…In four consecutive papers, three different batches of a polymer were investigated (Table 2) [39][40][41][42][43]. Similar to the work of Hoogenboom et al on homopoly(2-oxazoline)s [37], the standard deviation of the M n was approximately 5% of the average.…”

In-vitro cytotoxic activities of poly(2-ethyl-2-oxazoline)-based amphiphilic block copolymers prepared by CuAAC click chemistry

“…Up to now, various modification strategies for example, functional initiators or monomers, copolymerization and post-modification reactions are applied for the functionalization aliphatic polyesters [28,29]. Recently, poly(2-oxazoline)s have drawn attention with the finding of the potential biological and chemical favorability due to their some advantageous structural properties such as pH and temperature sensitive, ionic strength, chemical and biological stimuli [30][31][32][33][34]. These polymers can be obtained via living cationic ring opening polymerization (CROP) of 2-alkyl-oxazolines and functionalized by using either functional initiator or nucleophilic terminating agents [35][36][37][38][39].…”

Directed Functionalization of Halophenyl‐2‐oxazolines with TMPMgCl·LiCl

“…Thus, a solution of the indicated electrophile in THF (1.0 mL) was added dropwise and the reaction mixture stirred for 12 h. The reaction was quenched with saturated aqueous NH 4 Cl (10 mL), the products were extracted with ethyl acetate (3 ϫ 10 mL), the extracts washed with brine, dried with MgSO 4 , and concentrated. 135.1, 131.3, 129.9, 129.3, 127.9, 127.7, 124.4, 78.9, 68.6 4 (0.8 mol-%, 4.5 mg) in THF (1 mL) and a solution of corresponding aryl halide RX (1 mmol, 2 equiv.) were added, and the resulting mixture was stirred at 60°C overnight.…”

“…[1] In addition, 2-oxazoline derivatives have been used in smart polymer engineering [2,3] and in the formation of micelles. [4] The chiral derivatives are widely used as chiral auxiliaries [5] and ligands for asymmetric catalysis, with several applications in organic synthesis.…”