Fabrication and Characterization of a Porous Silicon Drug Delivery System with an Initiated Chemical Vapor Deposition Temperature-Responsive Coating.

This paper reports on the fabrication of a pSi-based drug delivery system, functionalized with an initiated chemical vapor deposition (iCVD) polymer film, for the sustainable and temperature-dependent delivery of drugs. The devices were prepared by loading biodegradable porous silicon (pSi) with a fluorescent anticancer drug camptothecin (CPT) and coating the surface with temperature-responsive poly(N-isopropylacrylamide-co-diethylene glycol divinyl ether) (pNIPAM-co-DEGDVE) or non-stimulus-responsive poly(aminostyrene) (pAS) via iCVD. CPT released from the uncoated oxidized pSi control with a burst release fashion (∼21 nmol/(cm(2) h)), and this was almost identical at temperatures both above (37 °C) and below (25 °C) the lower critical solution temperature (LCST) of the switchable polymer used, pNIPAM-co-DEGDVE (28.5 °C). In comparison, the burst release rate from the pSi-pNIPAM-co-DEGDVE sample was substantially slower at 6.12 and 9.19 nmol/(cm(2) h) at 25 and 37 °C, respectively. The final amount of CPT released over 16 h was 10% higher at 37 °C compared to 25 °C for pSi coated with pNIPAM-co-DEGDVE (46.29% vs 35.67%), indicating that this material can be used to deliver drugs on-demand at elevated temperatures. pSi coated with pAS also displayed sustainable drug delivery profiles, but these were independent of the release temperature. These data show that sustainable and temperature-responsive delivery systems can be produced by functionalization of pSi with iCVD polymer films. Benefits of the iCVD approach include the application of the iCVD coating after drug loading without causing degradation of the drug commonly caused by exposure to factors such as solvents or high temperatures. Importantly, the iCVD process is applicable to a wide array of surfaces as the process is independent of the surface chemistry and pore size of the nanoporous matrix being coated.

Combination of iCVD and porous silicon for the development of a controlled drug delivery system.

We describe a pH responsive drug delivery system which was fabricated using a novel approach to functionalize biodegradeable porous silicon (pSi) by initiated chemical vapor deposition (iCVD). The assembly involved first loading a model drug (camptothecin, CPT) into the pores of the pSi matrix followed by capping the pores with a thin pH responsive copolymer film of poly(methacrylic acid-co-ethylene dimethacrylate) (p(MAA-co-EDMA)) via iCVD. Release of CPT from uncoated pSi was identical in two buffers at pH 1.8 and pH 7.4. In contrast, the linear release rate of CPT from the pSi matrix with the p(MAA-co-EDMA) coating was dependent on the pH; release of CPT was more than four times faster at pH 7.4 (13.1 nmol/(cm(2) h)) than at pH 1.8 (3.0 nmol/(cm(2) h)). The key advantage of this drug delivery approach over existing ones based on pSi is that the iCVD coating can be applied to the pSi matrix after drug loading without degradation of the drug because the process does not expose the drug to harmful solvents or high temperatures and is independent of the surface chemistry and pore size of the nanoporous matrix.

Insights into thin, thermally responsive polymer layers through quartz crystal microbalance with dissipation.

The thermodynamics of temperature-responsive polymeric layers was analyzed using a two-state coil to globule model to which the van't Hoff relationship was applied. For soluble homopolymer poly(N-isopropylacrylamide (pNIPAAm), enthalpies of transition, ΔH(vH), were calculated using varations in ultraviolet-visible (UV-vis) spectroscopy with temperature to be 8400 ± 30 and 1652 ± 4 kJ mol-cooperative unit(-1) for standard synthesis and initiated chemical vapor deposition (iCVD), respectively. For the insoluble surface-bound layer of cross-linked iCVD poly(N-isopropylacrylamide-co-di(ethylene glycol) divinyl ether) [p(NIPAAm-co-DEGDVE)], ΔH(vH) was determined to be 810 ± 30 kJ mol-cooperative unit(-1) using quartz crystal microbalance with dissipation monitoring (QCM-D). Microcalorimetry measurements showed the enthalpies per mole NIPAAm monomer to be 5.8 ± 0.2, 3.5 ± 0.6, and 3.1 ± 0.3 kJ mol-NIPAAm(-1), resulting in cooperative unit sizes of 1460 ± 60, 470 ± 80, and 260 ± 30 monomer units for the standard pNIPAAm, iCVD pNIPAAm, and p(NIPAAm-co-DEGDVE) systems, respectively. These values indicate that both per monomer enthalpic contribution as well as cooperative unit size are primary factors contributing to the variations in van't Hoff enthalpies for the three systems studied. Diffusion of bovine serum albumin (BSA) into swollen p(NIPAAm-co-DEGDVE) films below its lower critical solution temperature was elucidated via QCM-D measurements. These data provided a calculated diffusion coefficient of (3.5 ± 0.1) × 10(-14) cm(2) s(-1) of BSA into the swollen hydrogel film with a mesh size of 6.0 ± 0.2 nm (compared to the hydrodynamic radius of BSA, r(H) = 3.36 nm).

Chemical vapor deposition of conformal, functional, and responsive polymer films.

Chemical vapor deposition (CVD) polymerization utilizes the delivery of vapor-phase monomers to form chemically well-defined polymeric films directly on the surface of a substrate. CVD polymers are desirable as conformal surface modification layers exhibiting strong retention of organic functional groups, and, in some cases, are responsive to external stimuli. Traditional wet-chemical chain- and step-growth mechanisms guide the development of new heterogeneous CVD polymerization techniques. Commonality with inorganic CVD methods facilitates the fabrication of hybrid devices. CVD polymers bridge microfabrication technology with chemical, biological, and nanoparticle systems and assembly. Robust interfaces can be achieved through covalent grafting enabling high-resolution (60 nm) patterning, even on flexible substrates. Utilizing only low-energy input to drive selective chemistry, modest vacuum, and room-temperature substrates, CVD polymerization is compatible with thermally sensitive substrates, such as paper, textiles, and plastics. CVD methods are particularly valuable for insoluble and infusible films, including fluoropolymers, electrically conductive polymers, and controllably crosslinked networks and for the potential to reduce environmental, health, and safety impacts associated with solvents. Quantitative models aid the development of large-area and roll-to-roll CVD polymer reactors. Relevant background, fundamental principles, and selected applications are reviewed.

Sharp Hydrophilicity Switching and Conformality on Nanostructured Surfaces Prepared via Initiated Chemical Vapor Deposition (iCVD) of a Novel Thermally Responsive Copolymer.

A novel thermally responsive copolymer p(NIPAAm-co-DEGDVE) is synthesized using the substrate independent method of iCVD and exhibits a sharp lower critical solution temperature (LCST) transition centered at ≈28.5 ± 0.3 °C determined via quartz crystal microbalance measurements with dissipation monitoring (QCM-D). Swelling with water below the LCST produces a reversible change of ≈3× in film thickness. The layer is conformal on nanostructured surfaces including MWCNT forests and electrospun nanofiber mats. Modified planar substrates exhibit ≈30°change in static contact angle over the LCST, while through conformal coating on nanostructured substrates changes in static contact angle up to 135° are achieved. Additionally, coated surfaces exhibit temperature sensitive BSA adsorption measured by QCM-D and is reversible as shown through fluorescence imaging of a coated electrospun nanofiber mat.

Infrared spectroscopy of competitive interactions between liquid crystals, metal salts, and dimethyl methylphosphonate at surfaces.

We report the use of Fourier transform polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) to characterize the influence of dimethyl methylphosphonate (DMMP) on the molecular interactions occurring within thin films of nitrile-containing liquid crystals supported on surfaces presenting metal perchlorate salts. Infrared spectra obtained using thin films of 4'-octyl-4-biphenylcarbonitrile (8CB) supported on copper(II) perchlorate salts reveal the nitrile groups of 8CB to be coordinated to the copper(II) on these surfaces, and subsequent exposure of the system to DMMP to result in the elimination of these coordinated nitrile groups. Concurrently, evidence of coordination of the phosphoryl group of DMMP with copper(II) is provided by measurement of a shift of the phosphoryl stretch from 1246 to 1198 cm(-1). In contrast, surfaces presenting nickel(II) perchlorate salts only weakly coordinate with DMMP [the phosphoryl peak shifts from 1246 to 1213 cm(-1) in the presence of nickel(II)], and exposure of 8CB to DMMP results in only partial loss of coordination of the nitrile groups of 8CB with nickel(II). These PM-IRRAS measurements and others reported in this article provide insights into the molecular origins of macroscopic ordering transitions that are observed when micrometer-thick films of nitrile-containing liquid crystals supported on copper(II) or nickel(II) perchlorate are exposed to DMMP: Upon exposure to DMMP, nematic phases of 4'-pentyl-4-biphenylcarbonitrile (5CB) supported on copper(II) perchlorate salts undergo ordering transitions, whereas 5CB supported on nickel(II) perchlorate salts do not. Our IR results support the hypothesis that these ordering transitions reflect the relative strengths of coordination interactions occurring between the 5CB, DMMP, and the metal salts at these interfaces.