Karyn L. Jarvis

Surface chemistry of porous silicon and implications for drug encapsulation and delivery applications

Porous silicon (pSi) has a number of unique properties that appoint it as a potential drug delivery vehicle; high loading capacity, controllable surface chemistry and structure, and controlled release properties. The native Si(y)SiH(x) terminated pSi surface is highly reactive and prone to spontaneous oxidation. Surface modification is used to stabilize the pSi surface but also to produce surfaces with desired drug delivery behavior, typically via oxidation, hydrosilylation or thermal carbonization. A number of advanced characterization techniques have been used to analyze pSi surface chemistry, including X-ray photoelectron spectroscopy and time of flight secondary ion mass spectrometry. Surface modification not only stabilizes the pSi surface but determines its charge, wettability and dissolution properties. Manipulation of these parameters can impact drug encapsulation by altering drug-pSi interactions. pSi has shown to be a successful vehicle for the delivery of poorly soluble drugs and protein therapeutics. Surface modification influences drug pore penetration, crystallinity, loading level and dissolution rate. Surface modification of pSi shows great potential for drug delivery applications by controlling pSi-drug interactions. Controlling these interactions allows specific drug release behaviors to be engineered to aid in the delivery of previously challenging therapeutics. Within this review, different pSi modification techniques will be outlined followed by a summary of how pSi surface modification has been used to improve drug encapsulation and delivery.

Hydrophobic plasma polymer coated silica particles for petroleum hydrocarbon removal.

In recent years, functionalized hydrophobic materials have attracted considerable interest as oil removal agents. This investigation has applied plasma polymerization as a novel method to develop hydrophobic and oleophilic particles for water purification. 1,7-Octadiene was plasma polymerized onto silica particles using a radio frequency inductively coupled reactor fitted with a rotating chamber. Plasma polymerized 1,7-octadiene (ppOD) films were deposited using plasma power of 40 W and monomer flow rate of 2 sccm, while polymerization time was varied from 5 to 60 min. The surface chemistry of ppOD coated particles was investigated via X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectroscopy, while Washburn capillary rise measurements were applied to evaluate the hydrophobicity and oleophilicity of the particles. The effectiveness of ppOD coated particles for the removal of hydrophobic matter from water was demonstrated by adsorption of motor oil, kerosene, and crude oil. Petroleum hydrocarbon removal was examined by varying removal time and particle mass. The morphology of oil-loaded ppOD coated particles was examined via environmental scanning electron microscopy observations. Increasing the polymerization time increased the concentration of hydrocarbon functionalities on the surface, thus also increasing the hydrophobicity and oil removal efficiency (ORE). The ppOD coated particles have shown to have excellent ORE. These particles were capable of removing 99.0-99.5% of high viscosity motor oil in 10 min, while more than 99.5% of low viscosity crude oil and kerosene was adsorbed in less than 30 s. Plasma polymerization has shown to be a promising approach to produce a new class of materials for a fast, facile, and efficient oil removal.

Plasma Polymer-Functionalized Silica Particles for Heavy Metals Removal

Highly negatively charged particles were fabricated via an innovative plasma-assisted approach for the removal of heavy metal ions. Thiophene plasma polymerization was used to deposit sulfur-rich films onto silica particles followed by the introduction of oxidized sulfur functionalities, such as sulfonate and sulfonic acid, via water-plasma treatments. Surface chemistry analyses were conducted by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectroscopy. Electrokinetic measurements quantified the zeta potentials and isoelectric points (IEPs) of modified particles and indicated significant decreases of zeta potentials and IEPs upon plasma modification of particles. Plasma polymerized thiophene-coated particles treated with water plasma for 10 min exhibited an IEP of less than 3.5. The effectiveness of developed surfaces in the adsorption of heavy metal ions was demonstrated through copper (Cu) and zinc (Zn) removal experiments. The removal of metal ions was examined through changing initial pH of solution, removal time, and mass of particles. Increasing the water plasma treatment time to 20 min significantly increased the metal removal efficiency (MRE) of modified particles, whereas further increasing the plasma treatment time reduced the MRE due to the influence of an ablation mechanism. The developed particulate surfaces were capable of removing more than 96.7% of both Cu and Zn ions in 1 h. The combination of plasma polymerization and oxidative plasma treatment is an effective method for the fabrication of new adsorbents for the removal of heavy metals.

Thermal Oxidation for Controlling Protein Interactions with Porous Silicon

Thermal oxidation of porous silicon (pSi) has been used to control interactions with three proteins; lysozyme, papain, and human serum albumin (HSA) enabling the influences of protein structure, molecular weight, and charge to be elucidated. Adsorption behavior was assessed via adsorption isotherms while the structures of adsorbed proteins were investigated using a bioactivity assay, FTIR, and zeta potential. Time-of-flight secondary ion mass spectrometry was used to examine protein pore penetration. High protein adsorption onto unoxidized pSi (240-610 microg/m(2)) was attributed to predominately hydrophobic interactions which resulted in structural changes of the adsorbed proteins and significant loss of bioactivity. Thermal oxidation at 400 and 800 degrees C significantly reduced protein adsorption (80-485 microg/m(2)) by reducing hydrophobicity. Oxidation of pSi modified the protein adsorption mechanisms to solely electrostatic attraction for positively charged proteins and structural rearrangement for negatively charged proteins. Adsorption via electrostatic attraction preserved protein bioactivity and zeta potential, thus inferring a retention of their native structure. In contrast, the negative charge and globular structure of HSA resulted in a loss of structure. We have demonstrated that thermal oxidation of pSi can be used to control protein interactions, adsorbed structure, and bioactivity.

Plasma polymerized allylamine coated quartz particles for humic acid removal

Allylamine plasma polymerization has been used to modify the surface of quartz particles for humic acid removal via an inductively coupled rotating barrel plasma reactor. Plasma polymerized allylamine (ppAA) films were deposited at a power of 25 W, allylamine flow rate of 4.4 sccm and polymerization times of 5-60 min. The influence of polymerization time on surface chemistry was investigated via X-ray photoelectron spectroscopy (XPS), time of flight secondary ion mass spectrometry (ToF-SIMS) and electrokinetic analysis. Acid orange 7 adsorption/desorption quantified the number of surface amine groups. Humic acid removal via ppAA quartz particles was examined by varying pH, removal time, humic acid concentration, and particle mass. Increasing the polymerization time increased the concentration of amine groups on the ppAA quartz surface, thus also increasing the isoelectric point. ToF-SIMS demonstrated uniform distribution of amine groups across the particle surface. Greatest humic acid removal was observed at pH 5 due to electrostatic attraction. At higher pH values, for longer polymerization times, humic acid removal was also observed due to hydrogen bonding. Increasing the initial humic acid concentration increased the mass of humic acid removed, with longer polymerization times exhibiting the greatest increases. Plasma polymerization using a rotating plasma reactor has shown to be a successful method for modifying quartz particles for the removal of humic acid. Further development of the plasma polymerization process and investigation of additional contaminants will aid in the development of a low cost water treatment system.

Aqueous and thermal oxidation of porous silicon microparticles: implications on molecular interactions.

Links between the mechanisms and kinetics of aqueous and dry thermal oxidation of porous silicon (pSi) microparticles have been investigated and the influence on molecular interaction established. zeta potential measurements have established the interplay between the dry oxidation state of pSi microparticles and their interfacial chemistry in aqueous solution, and Fourier transform infrared spectroscopy has demonstrated the effect of immersion time and oxidation temperature on surface chemistry. The influence of aqueous and thermal oxidation on molecular interactions and loading was investigated using methylene blue as a probe molecule. Aqueous immersion of pSi microparticles results in an initial increase in OySiH (y = 1-3) species with increasing immersion times, reducing O2SiH concentration, while O3SiH concentration remained constant. Thermal oxidation from 473 to 1073 K causes the gradual transition from SiySiHx to OySiH and finally OySiOH species. Both aqueous and thermal oxidations had an effect on the zeta potentials of pSi microparticles. Methylene blue discoloration occurred due to its reduction by the SiSiHx-terminated surface thereby demonstrating the reactivity of such species. Aqueous and thermal oxidations modify pSi microparticle surface chemistry, which has therefore shown to influence molecular interactions. Understanding the aqueous oxidation of pSi is crucial when loading pSi from aqueous solution due to its impact on molecular interactions. These molecular interactions play an important role in the loading of pSi since they dictate the attraction of the molecule toward the surface and therefore ultimately the loading level.

Surface chemical modification to control molecular interactions with porous silicon.

Interactions between porous silicon (pSi) particles and probe molecules were evaluated to determine the effect of pSi and probe molecule chemistry on adsorption. Methylene blue, ethyl violet and orange G dyes were chosen for investigation as they possess distinct functionalities and charges. Several distinct pSi surface species were produced via thermal oxidation at 200-800 °C and their effect on adsorption investigated. The adsorption mechanisms were elucidated from equilibrium adsorption and desorption isotherms. Methylene blue adsorption was attributed to electrostatic attraction where a gradual increase in adsorption with oxidation temperature was observed. Significant methylene blue desorption was observed at pH 3, confirming adsorption occurs via electrostatic attraction. Ethyl violet demonstrated an increase in plateau adsorption capacity and affinity with increased oxidation temperatures and adsorption was initially attributed to electrostatic attraction, however desorption of ethyl violet was not observed, thus indicating potential chemisorption. Orange G exhibited high affinity adsorption for Si(y)SiH(x) terminated surfaces but no orange G desorption was detected, indicating a chemisorption adsorption mechanism. It has been successfully demonstrated that the surface modification of pSi enabled the manipulation of molecular interactions. By interacting probe molecules with similar functionalities to drug molecule with pSi, greater understanding of drug-pSi interactions can be ascertained which are of great importance. pSi surface chemistry can be tailored to enable control over molecular interactions and ultimately dictate loading, encapsulation and release behavior.

Recent advances in porous silicon technology for drug delivery

Porous silicon (pSi) is a nanostructured carrier system that has received considerable attention over the past 10 years, for use in a wide variety of biomedical applications, including biosensing, biomedical imaging, tissue scaffolds and drug delivery. This interest is due to several key features of pSi, including excellent in vivo biocompatibility, the ease of surface chemistry modification and the control over its 3D porous network structure. With control of these physical parameters pSi has successfully been used for the delivery of a variety of therapeutics, ranging from small-molecule drugs to larger peptide/protein-type therapeutics. In this review, the authors provide a brief overview of pSi fabrication methods, particularly with regard to the need to passivate the highly reactive Si-Hx surface species of native pSi, typically via thermal oxidation, hydrocarbonization or hydrosilylation. This surface modification, in turn, controls both the loading and release of therapeutics. The authors will then report on specific case studies of leading examples on the use of pSi as a therapeutic-delivery system. Specifically, the first reported in vivo study that demonstrated the use of pSi to improve the delivery of a Biopharmaceutical Classification System Class 2 poorly soluble drug (indomethacin), by using thermally oxidized pSi, is discussed, as well as highlighting a study that determined the biodistribution of (18)F-radiolabeled thermally hydrocarbonized pSi after oral dosing. The authors also report on the development of composite pSi-poly(D,L-lactide-co-glycolide) microparticles for the controlled delivery of protein therapeutics. Finally, the use of pSi in the delivery of bioactives, such as the successful use of thermally carbonized pSi to deliver Melanotan II, an unspecific agonist for the melanocortin receptors that are involved in controlling fluid uptake is discussed. With a growing body of literature reporting the successful use of pSi to deliver a range of therapeutics, we are entering what may be a golden age for this drug-delivery system, which may finally see the long-held promises finally achieved.

Development of oxidized sulfur polymer films through a combination of plasma polymerization and oxidative plasma treatment.

A novel two-step process consisting of plasma polymerization and oxidative plasma treatment is introduced in this article for the first time for the fabrication of -SO(x)(H)-functionalized surfaces. Plasma-polymerized thiophene (PPT) was initially deposited onto silicon wafers and subsequently SO(x)(H)-functionalized using air or oxygen plasma. The effectiveness of both air and oxygen plasma treatments in introducing sulfur-oxygen groups into the PPT film was investigated as the plasma input specific energy and treatment time were varied. The surface chemistries of untreated and treated PPT coatings were analyzed by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectroscopy (ToF-SIMS), whereas spectroscopic ellipsometry was used to evaluate the film thickness and ablation rate. Surface chemistry analyses revealed that high concentrations of -SO(x)(H) functionalities were generated on the surface upon either air or oxygen plasma treatment. It was found that, at low plasma input energies, the oxidation process was dominant whereas, at higher energies, ablation of the film became more pronounced. The combination of thiophene plasma polymerization and air/oxygen plasma treatment was found to be a successful approach to the fabrication of -SO(x)(H)-functionalized surfaces.

Influence of Film Stability and Aging of Plasma Polymerized Allylamine Coated Quartz Particles on Humic Acid Removal

Plasma polymerized allylamine (ppAA) films have been successfully deposited on to the surface of quartz particles via a rotating barrel plasma reactor for humic acid removal. The films were deposited at a power of 25 W, allylamine flow rate of 4.4 sccm and polymerization times of 5 to 60 min. X-ray photoelectron spectroscopy was used to investigate the influence of short-term stirring in water and film age on surface chemistry. Stirring results in a reduction in the nitrogen concentration, which was greatest for shorter polymerization times. Film aging of up to 52 weeks appeared to result in a reduction in the concentration of C-N species. The influence of batch, recycling, and film age on humic acid removal was investigated. Humic acid removal appeared to be reproducible across three separate batches for polymerization times of 20 min or more, which was attributed to film thickness. Recycling of the ppAA films was most successful at pH 11 for up to 4 humic acid removal/regeneration cycles. Successful regeneration at pH 11 was attributed to electrostatic repulsion of the adsorbed humic acid molecules. Decreasing the pH of the regeneration solution reduced the number of successful regeneration cycles due to greater retention of adsorbed humic acid via electrostatic attraction. Film age appears to have minimal effect on humic acid removal where freshly deposited and 52-week-old films removed similar masses of humic acid. Successful production and development of ppAA coated quartz particles has resulted in a functional material that can be incorporated into a water treatment system to improve water quality.