We demonstrate the conjugation of the cancer drug doxorubicin (DOX) to poly(methacryloyloxyethyl phosphorylcholine) (polyMPC), linked by hydrazone groups, using (1) a one-pot ATRP/click sequence, and (2) a post-polymerization conjugation strategy. While the one-pot method gave polyMPC-DOX conjugates in a facile single step, post-polymerization conjugation gave higher-molecular-weight polymers with very high DOX loadings. DOX release from the polyMPC backbone was pH-dependent (faster at pH 5.0 than at pH 7.4) owing to the hydrazone linkage. Half-life values of DOX release ranged from 2 to 40 h at pH 5.0. Cell culture experiments showed that highly loaded polyMPC-DOX conjugates exhibited higher intracellular drug accumulation and lower half-maximal inhibitory concentration (IC(50)) values, while a polymer with 30 wt % drug loading showed a maximum tolerated dose in the range of 30-50 mg/kg DOX equivalent weight in healthy mice.

Segmented polyurethane multiblock polymers containing polydimethylsiloxane and polyether soft segments form tough and easily processed thermoplastic elastomers. Two commercially available examples, Elast-Eon E2A (denoted as E2A) and PurSil 35 (denoted as P35), were evaluated for molecular and mechanical stability after immersion in buffered water for up to 52 weeks at temperatures ranging from 37 to 85 °C. Dynamic mechanical spectroscopy experiments, performed in tension and shear, were used to characterize the linear viscoelastic properties of compression-molded (dry) specimens. Small-angle X-ray scattering measurements indicated a disorganized microphase-separated morphology for all test conditions. Upon aging in phosphate buffered saline, samples of E2A and P35 were analyzed by size exclusion chromatography (SEC) and tensile testing as a function of time and temperature. The absolute molar mass of each material prior to aging in water was determined by SEC using a multiangle light scattering detector. Aging at 85 °C and 52 weeks lead to a 67% and 50% reduction in molar mass from the original values for E2A and P35, respectively. We attribute the reduction in molar mass to hydrolysis of the polymer backbone and have evaluated the data using a pseudo-zero-order kinetics analysis. The temperature dependence of the extracted rate data is consistent with an activated (i.e., Arrhenius) process, and thus all the molar mass reduction data can be reduced to a single master curve. Concomitant with the reduction in molar mass, E2A and P35 transformed with aging from strain-hardening to strain-softening materials, characterized by substantially reduced tensile strength (stress at failure) and ultimate elongation (strain at failure) relative to the original properties.

We report the synthesis of hydrophilic, zwitterionic copolymers containing pendent disulfide and dithiol groups along a phosphorylcholine methacrylate backbone. These novel copolymers were prepared by controlled free radical copolymerization of methacryloyloxyethyl phosphorylcholine (MPC) and the methacrylate of lipoic acid (LA), using reversible addition−fragmentation chain transfer (RAFT) polymerization, followed by reduction of the disulfides to give dihydrolipoic acid (DHLA) pendent groups. Poly(MPC-co-DHLA) proved useful for surface functionalization of gold nanorods (Au NRs), resulting in removal of the cationic surfactant stabilizing layer present initially on the Au NRs. Au NRs coated with poly(MPC-co-DHLA) proved stable against challenging conditions, and resisted cyanide ion digestion. Au NRs coated with poly(MPC-co-DHLA) also showed nonfouling properties resulting from their surface coating, and the noncytotoxicity of these structures was confirmed in the presence of live cells. The novel polymer materials and the methodology we describe hold promise for enabling new opportunities that utilize surface-coated metallic and semiconductor nanostructures in both materials and biological applications.

Novel polymer-drug conjugates, consisting of zwitterionic poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) as the polymer component, and camptothecin (CPT) as the drug, were prepared by two methods. In one case, CPT was transformed by acylation into a functional initiator for copper catalyzed atom transfer radical polymerization (ATRP), and polyMPC was grown from this therapeutic initiator. In the other case, a one-pot ATRP-"click" conjugation strategy was employed to synthesize novel polyMPC structures containing multiple copies of the drug pendant to the zwitterionic polymer chain. The latter method allows polyMPC-graft-CPT conjugates to be prepared with a high weight percent drug loading (up to 14% CPT) with excellent solubility in pure water (>250 mg/mL). The linkage chemistry chosen between the polyMPC backbone and the pendant drugs proved critically important for assuring drug release within a time frame reasonable to consider these structures as a platform for injectable cancer therapeutics. Liberation of the drug from the polymer backbone was monitored by high-performance liquid chromatography, using size-exclusion and reverse-phase columns, and the toxicity of the polymer-drug conjugates was examined in cell culture against breast (MCF7), ovarian (OVCAR-3), and colorectal (COLO 205) cancer cell lines.

A medical grade, commercially available polyether urethane, denoted PEU 80A, was exposed to both real time (37°C) and temperature accelerated (55, 70, and 85°C) hydrolysis conditions for a period of one year in vitro. Neutral pH and deoxygenated phosphate buffered saline exposure conditions mitigated the well-studied oxidation reaction, allowing for evaluation of hydrolysis events. The hydrolytic sensitivity of the PEU 80A was analyzed using nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography−mass spectrometry (LC-MS), and size exclusion chromatography (SEC). We showed that the only obvious backbone chain scission event occurred at the urethane (carbamate) linkages. Using the widely applied Arrhenius model for accelerated predictions involving chemical reactions, we predict that a 50% reduction in PEU 80A molar mass would require approximately 80 years of exposure at 37°C in the presence of excess water. The activation energy for urethane linkage hydrolysis of ∼90 kJ mol −1 extracted from this analysis is in agreement with previous reports, where the change in molar mass was accounted for by chain scission events at the urethane linkage. A similar analysis of polydimethylsiloxane (PDMS) modified urethanes PurSil 35 (P35) and ElastEon 2A (E2A), exposed to identical hydrolysis conditions, gave an equivalent activation energy for urethane hydrolysis, indicating that hydrolytic cleavage of backbone urethane linkages is not significantly impacted by the incorporation of PDMS into the urethane structure. However, as previously reported, the activation energy governing the observed molar mass reduction in these PDMS-urethanes is one-third that measured for the hydrolytic chain scission events at the urethane bond. These combined results suggest that the reaction(s) responsible for the observed molar mass changes in the PDMS-urethanes is not due to hydrolytic cleavage at the urethane linkages.