Blends of Paclitaxel with POSS-Based Biodegradable Polyurethanes: Morphology, Miscibility, and Specific Interactions

Abstract

The morphology, miscibility, and specific interactions of paclitaxel (PTx) with a family of polyhedral oligosilsesquioxane (POSS)-based biodegradable thermoplastic polyurethanes (POSS TPUs) were investigated systematically using wide-angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). These POSS TPUs incorporate an alternating multiblock structure formed by POSS hard segments and the soft segments composed of polylactide/caprolactone copolymer (P(DLLA-co-CL)). They feature variable poly(ethylene glycol) (PEG) content from 0 to 14 wt % through adjusting the poly(ethylene glycol) (PEG) molecular weight in P(DLLA-co-CL) soft segments of fixed molar mass of M _ n = 12 kg/mol and further to 52 wt % utilizing pure PEG M _ n = 1 kg/mol in the soft segments. Using WAXD, it was found that PTx is amorphous in all proportions in the PTx/POSS TPU blends prepared using a solutioncasting method. Interestingly, the PTx not only exhibits excellent miscibility in all of these PTx/POSS TPU blends over the whole range of the drug concentration, but also serves as an antiplasticizer by increasing the blend T g gradually from the polymer T g up to the T g of amorphous PTx. The T g -composition dependences in these blends were well fitted by the Gordon-Taylor equation. The glass transition breadth of the blends increases significantly only for drug concentrations higher than 50 wt % for most of the POSS TPUs, suggesting some spatial heterogeneity at these high drug concentrations. On the other hand, the slight increment of the blend melting temperature, T m , and latent heat, ΔH, indicates enhanced phase separation between the POSS hard segments and the TPU soft segments upon drug incorporation. Gordon-Taylor analysis and FTIR results confirm that the PEG incorporated in the POSS TPUs exhibits strong H-bonding interactions with the PTx. Although PEG can promote the favorable interactions in the PTx/POSS TPU blends, we showed that the more hydrophobic LA/CL repeat units are still required in the soft segments in order to achieve molecular-level miscibility. This systematic investigation of the PTx/POSS TPU systems may be of great value to design plasticizer/antiplasticizer for new polymer materials with controlled and tailored properties, especially for those PLA-or PCL-based biodegradable polymer systems.

Hot melt mixing and foaming of soluplus® and indomethacin

“…The impact of incorporated low‐molecular weight APIs on a polymer's T g can be found in literature [20–23]. In general, a shift in T g is expected when the API is dissolved into the polymeric excipient, on the other hand the polymer's T g will not change if the two compounds are not in one phase and the API remains crystalline.…”

A Nanocage for Nanomedicine: Polyhedral Oligomeric Silsesquioxane (POSS)

“…[55] Furthermore, recent studies in the design of degradable polymers suggest overall improvements in the miscibility of paclitaxel over a range of concentrations, which can be fine tuned by specific interactions of degradable POSS-TPUs. [56] POSS-PCU has been characterized and assessed for biomedical applications in general, and for cardiovascular applications in particular, and the results of such studies reveal that POSS-PCU nanocomposites contain enhanced physical and chemical characteristics which create a technology platform for biomedical applications. This polymer is currently being used in the design, fabrication, and manufacture of medical devices, including microvascular beds for organ tissue (including liver), muscle, cartilage, and breast implants, [50] materials for coating quantum dot nanocrystals for cancer detection, improved contrast agents for magnetic resonance imaging (MRI), A) The surface can be modified by grafting specific bio-active peptide motifs or other ligands or receptors into POSS-PCU.…”

Thermoplastic polyurethane synthesis using POSS as a chain modifier

“…The absorption peak observed between 3043-3041 cm -1 is associated with the presence of aromatic rings in the MDI, HQEE and organic terminations of the POSS (Figure 1). Peaks immediately below the 3000 cm -1 region show the presence of C-H bonds, confirmed in the region of 1455-1414 cm -1 [15] . The characteristic N=C=O peak at approximately 2253 cm -1 was absent in Figure 2, suggesting a complete conversion of the isocyanate terminations presents on MDI reagent in Figure 1a into urethane and urea groups.…”

“…According to the Flory-Huggins theory 31 , a melting temperature increase indicates a comparably unfavorable interaction between components, in this case, the TPU and POSS. Considering this theory, the addition of POSS drives stronger phase separation of the TPU hard segment from the amorphous phase in POSS TPUs, leading to enhanced POSS crystallization 15 . The melting enthalpy showed appreciable changes only for TPUs with 0.4% addition of POSS; the glass transition temperature of flexible phase (T g-f ) values consequently being higher due to the lower chain mobility.…”

“…The average size of the nucleus is 1.5 nm, and it is surrounded by functional organic groups. The POSS nanoscopic size allows reinforcement of the polymeric segments in which it is included, controlling the chain mobility at the molecular level 15 . These effects are related to the surface area and chemical interactions imposed by the nanoreinforcement of the polymeric chain, and its effect is analogous to the macroscopic reinforcement obtained by the addition of fibers to a polymeric matrix in composite structures 16,17 .…”