Natural Rubber Latex Foam Reinforced with Micro- and Nanofibrillated Cellulose via Dunlop Method.

Natural rubber latex foam (NRLF) was reinforced with micro- and nanofibrillated cellulose at a loading content of 5-20 parts per hundred of rubber (phr) via the Dunlop process. Cellulose powder from eucalyptus pulp and bacterial cellulose (BC) was used as a microcellulose (MC) and nanocellulose (NC) reinforcing agent, respectively. NRLF, NRLF-MC, and NRLF-NC exhibited interconnected macroporous structures with a high porosity and a low-density. The composite foams contained pores with sizes in a range of 10-500 µm. As compared to MC, NC had a better dispersion inside the NRLF matrix and showed a higher adhesion to the NRLF matrix, resulting in a greater reinforcement. The most increased tensile strengths for MC and NC incorporated NRLF were found to be 0.43 MPa (1.4-fold increase) and 0.73 MPa (2.4-fold increase), respectively, by reinforcing NRLF with 5 phr MC and 15 phr NC, whereas the elongation at break was slightly reduced. Compression testing showed that the recovery percentage was improved to 34.9% (1.3-fold increase) by reinforcement with 15 phr NC, whereas no significant improvement in the recovery percentage was observed with MC. Both NRLF-MC and NRLF-NC presented hydrophobic surfaces and good thermal stability up to 300 °C. Due to their highly porous structure, after a prolong immersion in water, NRLF composites had high water uptake abilities. According to their properties, the composite foams could be further modified for use as green absorption or supporting materials.

Octadecyltrichlorosilane Incorporated Alginate Micro-granules as Sustained-Release Carriers for Small Hydrophilic Molecules.

BACKGROUND: Hydrogels are excellent drug carriers, but their inability to retain hydrophilic drugs for a prolonged period of time has greatly limited their usage. Research has mostly focused on intricate designs and manipulations of hydrogels to expand their applications in drug delivery. OBJECTIVE: In this study, a simple approach by incorporating a hydrophobic agent, octadecyltrichlorosilane (OTS), to alginate hydrogel micro-granules (Alg-Ms), was investigated as an effective technique to prolong the release of small hydrophilic drugs. METHODS: Sodium Benzoate (SB), a highly water-soluble antimicrobial and anti-inflammatory compound, was used as a model drug. The presence of hydrophobic OTS impeded swelling of these OTS incorporated Alg-Ms (OTS-Alg-Ms), hence sustaining the release of SB. RESULT: The release data was fitted with Ritger-Peppas and Peppas-Sahlin models and the results showed that SB released from OTS-Alg-Ms with higher OTS content was mainly controlled by Fickian diffusion; with a lower OTS content, OTS-Alg-Ms swelled more easily, the combined diffusion and swelling led to a faster SB release. CONCLUSION: Thus, by simply tuning the OTS concentration in the solution where Alg-Ms were briefly submerged in a predefined release period, from hours to a few days, small hydrophilic drugs from these OTS-Alg-Ms could be successfully achieved.

Layer-by-layer Polyelectrolytes Coating of Alginate Microgels for Sustained Release of Sodium Benzoate and Zosteric Acid.

The potential of sustaining release of very small (Mw < 250 g/mol) hydrophilic drugs up to several days from layer-by-layer (LbL) polyelectrolyte coated alginate microgels (Alg-Ms) was investigated. One purpose is to minimize post-surgical adhesions, which develop in 12 h to 3 days after surgery. The LbL polyelectrolyte layer would serve as a diffusion barrier for their release. The LbL polyelectrolyte bilayers were prepared using poly(allylamine) (PAH) and poly(styrene sulfonate) (PSS). Sodium benzoate (NaB, Mw = 144 g/mol) and zosteric acid (ZA, Mw = 244 g/mol), two anti-inflammatory and anti-microbial compounds, were used as model drugs. A higher number of PAH/PSS bilayer lead to a greater sustained release of both drugs, and with 4 bilayers, the release of NaB and ZA was prolonged from 24 h to 72 h and 120 h, respectively. Fitting the data to the Ritger-Peppas' equation showed that as the bilayer number increased, the release constant and/or exponent decreased, indicating the LbL PAH/PSS bilayer effectively reduced the permeability of these two very small hydrophilic drugs. The ability to prolong the release of such small hydrophilic molecules, which has rarely been investigated previously, would find broad applications in fields such as anti-adhesion treatment and antifouling coatings.

Alignment of inducible vascular progenitor cells on a micro-bundle scaffold improves cardiac repair following myocardial infarction.

Ischemic heart disease is still the leading cause of death even with the advancement of pharmaceutical therapies and surgical procedures. Early vascularization in the ischemic heart is critical for a better outcome. Although stem cell therapy has great potential for cardiovascular regeneration, the ideal cell type and delivery method of cells have not been resolved. We tested a new approach of stem cell therapy by delivery of induced vascular progenitor cells (iVPCs) grown on polymer micro-bundle scaffolds in a rat model of myocardial infarction. iVPCs partially reprogrammed from vascular endothelial cells (ECs) had potent angiogenic potential and were able to simultaneously differentiate into vascular smooth muscle cells (SMCs) and ECs in 2D culture. Under hypoxic conditions, iVPCs also secreted angiogenic cytokines such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) as measured by enzyme-linked immunosorbent assay (ELISA). A longitudinal micro-scaffold made from poly(lactic-co-glycolic acid) was sufficient for the growth and delivery of iVPCs. Co-cultured ECs and SMCs aligned well on the micro-bundle scaffold similarly as in the vessels. 3D cell/polymer micro-bundles formed by iVPCs and micro-scaffolds were transplanted into the ischemic myocardium in a rat model of myocardial infarction (MI) with ligation of the left anterior descending artery. Our in vivo data showed that iVPCs on the micro-bundle scaffold had higher survival, and better retention and engraftment in the myocardium than free iVPCs. iVPCs on the micro-bundles promoted better cardiomyocyte survival than free iVPCs. Moreover, iVPCs and iVPC/polymer micro-bundles treatment improved cardiac function (ejection fraction and fractional shortening, endocardial systolic volume) measured by echocardiography, increased vessel density, and decreased infarction size [endocardial and epicardial infarct (scar) length] better than untreated controls at 8 weeks after MI. We conclude that iVPCs grown on a polymer micro-bundle scaffold are new promising approach for cell-based therapy designed for cardiovascular regeneration in ischemic heart disease.

Amino Acid-Based Zwitterionic Polymer Surfaces Highly Resist Long-Term Bacterial Adhesion.

The surfaces or coatings that can effectively suppress bacterial adhesion in the long term are of critical importance for biomedical applications. Herein, a group of amino acid-based zwitterionic polymers (pAAZ) were investigated for their long-term resistance to bacterial adhesion. The polymers were derived from natural amino acids including serine, ornithine, lysine, aspartic acid, and glutamic acid. The pAAZ brushes were grafted on gold via the surface-initiated photoiniferter-mediated polymerization (SI-PIMP). Results show that the pAAZ coatings highly suppressed adsorption from the undiluted human serum and plasma. Long-term bacterial adhesion on these surfaces was investigated, using two kinds of representative bacteria [Gram-positive Staphylococcus epidermidis and Gram-negative Pseudomonas aeruginosa] as the model species. Results demonstrate that the pAAZ surfaces were highly resistant to bacterial adhesion after culturing for 1, 5, 9, or even 14 days, representing at least 95% reduction at all time points compared to the control unmodified surfaces. The bacterial accumulation on the pAAZ surfaces after 9 or 14 days was even lower than on the surfaces grafted with poly[poly(ethyl glycol) methyl ether methacrylate] (pPEGMA), one of the most common antifouling materials known to date. The pAAZ brushes also exhibited excellent structural stability in phosphate-buffered saline after incubation for 4 weeks. The bacterial resistance and stability of pAAZ polymers suggest they have good potential to be used for those applications where long-term suppression to bacterial attachment is desired.

Surface immobilization of thermo-responsive poly(N-isopropylacrylamide) by simple entrapment in a 3-aminopropyltriethoxysilane network.

In a previous study, we demonstrated the feasibility of retaining poly(N-isopropylacrylamide) (pNIPAAm) on hydroxylated surfaces by spin-coating a blend of pNIPAAm with a small amount of 3-aminopropyltriethoxysilane (APTES), an organosilane, followed by thermal annealing. In this study, we detail the conditions for retaining pNIPAAm films by APTES. Our results show that the difference in surface energy between pNIPAAm and APTES in the blended film resulted in the segregation of APTES molecules to the film/substrate interface, as verified by XPS, during annealing, and the segregated APTES molecules cross-linked to form the APTES network, thus entrapping pNIPAAm. The retained pNIPAAm films (25-35 nm) exhibited thermo-responsive behavior, determined by water contact angles and film thickness in water at temperatures above and below the lower critical solution temperature of pNIPAAm, as well as good cell attachment and rapid detachment (<10 minutes). The gained insights would allow a better design of these thermo-responsive surfaces for cell sheet engineering and other relevant applications.

Modification of Bacterial Cellulose with Organosilanes to Improve Attachment and Spreading of Human Fibroblasts.

Bacterial Cellulose (BC) synthesized by Acetobacter xylinum has been a promising candidate for medical applications. Modifying BC to possess the properties needed for specific applications has been reported. In this study, BCs functionalized by organosilanes were hypothesized to improve the attachment and spreading of Normal Human Dermal Fibroblast (NHDF). The BC gels obtained from biosynthesis were dried by either ambient-air drying or freeze drying. The surfaces of those dried BCs were chemically modified by grafting methyl terminated octadecyltrichlorosilane (OTS) or amine terminated 3-aminopropyltriethoxysilane (APTES) to expectedly increase hydrophobic or electrostatic interactions with NHDF cells, respectively. NHDF cells improved their attachment and spreading on the majority of APTES-modified BCs (∼70-80% of area coverage by cells) with more rapid growth (∼2.6-2.8× after incubations from 24 to 48h) than on tissue culture polystyrene (∼2×); while the inverse results (< 5% of area coverage and stationary growth) were observed on the OTS-modified BCs. For organosilane modified BCs, the drying method had no effect on in vitro cell attachment/spreading behaviors.

Mechanically strong hybrid double network hydrogels with antifouling properties.

The development of mechanically tough and biocompatible polymer hydrogels has great potential and promise for many applications. Herein, we synthesized a new type of hybrid physically-chemically crosslinked Agar/PAM double network (DN) hydrogel using a simple, one-pot method. Agar/PAM gels are designed with desirable/balanced mechanical properties by varying the network-forming parameters. Among them, a strong Agar/PAM DN gel achieves the highest tensile stress of 3.3 MPa at failure strain of 2400%, while a tough DN gel achieves the tensile strain of 3700% at failure stress of 2.8 MPa. Besides excellent mechanical properties, Agar/PAM DN hydrogels exhibited excellent antifouling properties to highly resist protein adsorption, cell adhesion, and bacterial attachment, as well as the free shapeable property to form any complex shapes. The relationship between mechanical properties and antifouling performance was discussed. We hope that the combination of the mechanical and antifouling properties in Agar/PAM gels will make them as promising "biomimetic" materials for many bio-inert applications.

Applicability of the extended Derjaguin-Landau-Verwey-Overbeek theory on the adsorption of bovine serum albumin on solid surfaces.

Protein adsorption is the prerequisite for bacterial attachment and cellular adhesion, which are critical for many biomedical applications. To understand protein adsorption onto substrates, predictive models are generally informative prior to experimental studies. In this study, the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory was employed to determine whether or not it could interpret the protein adsorption behaviors. The experimental results of fluorescein isothiocyanate labeled bovine serum albumin (BSA) adsorbed on six different surfaces: glass, octadecyltrichlorosilane modified glass, 2-[methoxypoly(ethyleneoxy)propyl]trimethoxy-silane (PEG)-modified glass, polystyrene, poly(dimethylsiloxane), and poly(methyl methacrylate) were utilized. The XDLVO interaction energy curves, especially from the contribution of acid-base interactions, obtained using the surface properties of substrates and BSA molecules qualitatively predict/interpret the protein adsorption behaviors on these surfaces. Some derivation of the experimental results from the prediction was noticed for the glass and the PEG-modified glass. When including a hydration layer to the PEG-modified glass surface, the nonfouling result of such surface by proteins was also elucidated by the XDLVO theory.

Applicability of Washburn capillary rise for determining contact angles of powders/porous materials.

The Washburn capillary rise (WCR) technique has been widely utilized for determining contact angles of powders or porous materials; however, there are concerns regarding powder size and powder packing, especially for materials that exhibit large contact angle hysteresis. In this paper, some of these concerns were addressed. Due to the large water contact angle hysteresis on flat nylon 6/6 films, these films were ground into powders of different sizes and then used as model packing materials. The powders were packed in glass tubes to result in various packing structures that affected the penetration (i.e. advancing) rate of the test liquids. While all advancing contact angles obtained from WCR were found to be overestimated, more reasonable values were resulted when relatively large powders (e.g. 500-2000 µm) were used to pack the tubes. With larger powders, the packing contained bigger voids and consequently lead to slower penetration rates of the liquids, hence a relatively smaller advancing contact angle. The smaller advancing contact angle obtained from the slower advancing rate was also observed by using the sessile drop method. To verify the applicability of using large powders (500-2000 µm) for contact angle determination by using WCR, the advancing water contact angles of a bacterial cellulose/alginate composite sponge (BCA) with and without UV/ozone treatment were measured. The results showed that by using relatively large powders, WCR could be applied to obtain a reasonable advancing contact angle and assess the wettability change of complex porous materials.

Effect of rhamnolipids on initial attachment of bacteria on glass and octadecyltrichlorosilane-modified glass.

Bacterial attachment on solid surfaces has various implications in environmental, industrial and medical applications. In this study, the effects of rhamnolipid biosurfactants on initial attachment of bacteria on hydrophilic glass and hydrophobic octadecyltrichlorosilane (OTS) modified glass were evaluated under continuous-flow conditions. The bacteria investigated were three Gram-negative species Pseudomonas aeruginosa, Pseudomonas putida, and Escherichia coli, and two Gram-positive species Staphylcoccus epidermidis and Bacillus subtilis. Rhamnolipids, at 10 and 200 mg/l, significantly reduced the attachment of all but S. epidermidis on both glass and OTS-modified glass. For S. epidermidis rhamnolipids reduced the attachment on OTS-modified glass but not on glass. Studies were further done to identify the mechanism(s) by which rhamnolipids reduced the cell attachment. The following potential properties of rhamnolipids were investigated: inhibition of microbial growth, change of cell surface hydrophobicity, easier detachment of cells already attached to substratum, and modification of substratum surface properties. Results showed that rhamnolipids were ineffective for the latter two effects. Rhamnolipids, up to 200mg/l, inhibited the growth of B. subtilis, S. epidermidis and P. aeruginosa PAO1 but not the growth of E. coli, P. putida and P. aeruginosa E0340. Also, rhamnolipids tended to increase the hydrophobicity of P. aeruginosa PAO1 and E. coli, decrease the hydrophobicity of P. putida and S. epidermidis, and have no clear effect on the hydrophobicity of B. subtillis. These trends however did not correlate with the observed trend of cell attachment reduction. The responsible mechanism(s) remained unknown.

Evaluation of the natural product antifoulant, zosteric acid, for preventing the attachment of quagga mussels--a preliminary study.

The effectiveness of zosteric acid, a natural antifoulant from the marine seagrass Zostera marina, in preventing the attachment of quagga mussels, a biofouling bivalve, was investigated. Animals were exposed to water containing zosteric acid ranging from 0 to 1000 ppm, and their attachment to the container glass walls was tracked with time. 500 ppm zosteric acid was not effective at detaching animals that had already attached, but was able to prevent the attachment of most unattached animals for two days. The anti-fouling effect increased with higher concentration. Low concentrations (250 ppm and below) were not effective at preventing attachment; however, 1000 ppm zosteric acid prevented attachment of mussels for the first three days of zosteric acid exposure, and only 20% of the mussels were attached by day 4. In contrast, animals in control (no zosteric acid) solutions began to attach within one day. In conclusion, zosteric acid is an effective natural product deterrent of attachment of a biofouling bivalve.

Initial bacterial attachment in slow flowing systems: effects of cell and substrate surface properties.

Bacterial biofilm can have significant effects on the behaviors and/or performance of natural and man-made systems. Understanding the factors governing initial bacterial attachment is critical to biofilm management. In this study, the initial attachment of three bacteria, Pseudomonas aeruginosa, Escherichia coli and Pseudomonas putida, on two substrates, glass and octadecyltrichlorosilane (OTS) modified glass, was examined in flow chambers. The flow chambers were designed and operated to mimic slow moving water bodies and minimize the gravitational settlement of cells. The hydrophobicity of bacterial surface was evaluated by partitioning of cells to the water-hexadecane interface and the liquid contact angles on cell layers collected on filter papers. On the more hydrophilic glass surface, the attachment trend was found to be E. coli>P. putida>P. aeruginosa, while the opposite trend was observed on the hydrophobic, OTS modified surface. The attachment trend on glass could be explained by the magnitude of the negative interaction energy at secondary minima, as predicted by the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory. The much higher attachments of P. aeruginosa and P. putida on the OTS-modified substrate, on the other hand, suggested that these cells could overcome the energy barrier between the primary and secondary minima of interaction energy to become attached to the primary minimum. The extent of primary-minimum attachment appeared to correlate with the scale of the energy barrier, with higher attachments in the bacteria-substrate combinations of lower energy barriers. The study generated important insights into the effects of cell and substrate surface properties on initial bacterial attachment.

Generation of contact-printing based poly(ethylene glycol) gradient surfaces with micrometer-sized steps.

A surface with a density gradient of poly(ethylene glycol) (PEG) is an attractive substrate for combinatorial studies of biological phenomena. In this study, the generation of discrete step-wise density gradients of PEG utilizing a contact-printing approach is reported. The step-wise gradient template is achieved by contact-printing n-octadecyltrichlorosilane (OTS) to a glass from a hemispherical elastomeric stamp when the stamp is brought into contact with the substrate, and then step-wisely increasing the contact area as the corresponding contact-printing time for the step decreases. A PEG-silane is then used to backfill the unoccupied spaces of the contact printed OTS gradient to generate the OTS-PEG density gradient. Various characterizations, including water contact angle measurement, lateral force microscopy, and X-ray photoelectron spectroscopy, are conducted and confirmed that the surface coverage of OTS increases (or the coverage of PEG decreases) with the increase of contact-printing time of OTS. The step-wise gradient is illustrated by adsorption of a bovine serum albumin labeled with fluorescein isothiocyanate and subsequent attachment of fibroblasts. The amounts of protein adsorption and cellular attachment increase with the decrease of the surface coverage of PEG.

Dewetting of polystyrene thin films on poly(ethylene glycol)-modified surfaces as a simple approach for patterning proteins.

A simple technique for patterning proteins utilizing dewetted polystyrene (PS) droplets is demonstrated. A polystyrene thin film was spin coated on a poly(ethylene glycol) (PEG) silane-modified surface. As the PS film dewets from the surface, upon annealing, to form droplets, the PEG-silane-modified surface is exposed, which retains its capability to resist protein adsorption, and the PS droplets allow the selective adsorption of proteins. In contrast to the undewetted flat PS film, the droplet surface had a greater amount of adsorbed proteins. Atomic force microscopy scans reveal that the roughness of the droplet surface is higher, and a multilayer of proteins results on the droplet surface. Moreover, micro- and nanoscale droplet patterns can easily be achieved by tuning the thickness of PS thin films. Because dewetting approaches for generating ordered dewetting droplets have been successfully generated by others, those approaches could be easily combined with this technique to fabricate ordered protein patterns.

Dynamic contact angle in rim instability of dewetting holes.

The effects of dynamic contact angle (thetad), between a substrate and the melt of a dewetting polymer thin film, on the evolution of rim instabilities of dewetting holes were reported. Various thetad's were achieved by covering SiOx surfaces with different coverage of octadecyltrichlorosilane. On each surface, the morphology of the dewetting holes was examined in detail as the hole grew to a certain size. Rim instabilities, in terms of undulations in both r and z directions, became more pronounced as thetad increased, under which condition, narrower and higher rims were also observed. Experimentally, atomic force microscopic scans of the rim were used to obtain the rim profile, which was predicted using thetad. The predicted rim profile was used, in combination with the analysis of Rayleigh instability of a cylindrical fluid, to interpret the rim instability. The model captures the basic trend of the rim instability dependency on thetad. The study demonstrates the importance of the substrate properties on the rim instability and the destabilization of polymer thin films during hole growth.

Assessment of antifouling effectiveness of two natural product antifoulants by attachment study with freshwater bacteria.

UNLABELLED: GOAL, SCOPE, BACKGROUND: The traditional solution for keeping unwanted organisms from attaching to submerged surfaces is to apply anti-fouling coatings. The most common antifoulant was tributyltin (TBT). TBT systems were highly effective but were also toxic to non-target organisms. The use of the TBT based coatings will be completely banned by January 1, 2008. Therefore, there is an urgent need to seek out suitable non-toxic alternatives. METHODS: The aim of this work was to evaluate the effectiveness of capsaicin and zosteric acid as natural product antifoulants (NPAs) in deterring bacterial attachment. Two fresh water bacteria systems Pseudomonas putida (Pp) and bacteria isolated from Lake Erie (LE) were used to assess the attachment when the NPAs dispersed in the water. Effectiveness was ascertained based on the decrease in microbial attachment, limited toxicity, and minimum alteration of the coatings properties. RESULTS AND DISCUSSION: A significant inhibition of bacteria attachment was achieved when aqueous capsaicin concentration was increased from 0 to 40 mg/L. For instance, after 14 days the LE system depicted 93.5% and 98.5% less biofilm coverage for 20 mg/L and 40 mg/L capsaicin, respectively when pared to systems without NPA. Biofilm coverage was reduced by 92.5% and 98.2%, respectively with 50 mg/L and 500 mg/L zosteric acid. CONCLUSIONS: Both capsaicin and zosteric acid was effective at preventing bacteria attachment. As the NPA aqueous concentration increased, biofilm formation decreased. Evaluating changes in aqueous pH, conductivity, dissolved oxygen, aqueous microbial population and biofilm formation suggested that the primary antifoulant mechanism of these two NPAs was to block the bacteria's active sites versus posing a lethal level. RECOMMENDATION AND PERSPECTIVE: From the attachment study, zosteric acid appeared to be more effective in preventing bacterial attachment when the NPAs were dispersed in the aqueous environment. For practical applications, the antifoulant needs to be incorporated into a coating and have a slow release rate. Thus the ability to successfully incorporate zosteric acid into a coating, without deterring bacterial attachment, needs to be investigated.

Effectiveness of sodium benzoate as a freshwater low toxicity antifoulant when dispersed in solution and entrapped in silicone coatings.

The traditional solution for preventing organisms from attaching to submerged surfaces is to apply antifouling coatings or biocides. Based on the varied defence mechanisms exhibited by biofilms, the antifoulant needs to prevent bacterial attachment during the early stages of biofilm formation. The potential of benzoic acid and sodium benzoate (NaB) as antifoulants for deterring freshwater bacterial attachment was evaluated with the antifoulants dispersed in solution or entrapped in silicone coatings. Effectiveness was based on the decrease in microbial attachment, limited toxicity, and minimum alteration of the properties of the coatings. The optimal NaB concentration when dispersed in solution, 700 mg l-1, resulted in a biofilm surface coverage of only 3.34% after four weeks. The model silicone, Sylgard 184, demonstrated a better overall performance than the commercial coating, RTV11. Sylgard 184 containing sodium benzoate had 41-52% less biofilm in comparison to the control Sylgard 184, whereas both the control and NaB-entrapped RTV11 coatings had significant biofilm coverage.

Incorporating zosteric acid into silicone coatings to achieve its slow release while reducing fresh water bacterial attachment.

Biofouling has posed serious problems in maritime industry including increased fuel consumptions, economic loss from ship-hull maintenances, contamination of drinking water, and serious corrosion for mechanical instruments. Minimizing the attachment of bacteria and formation of biofilm could be advantageous in reducing the early stages of biofouling. Zosteric acid, a natural product present in eelgrass, was found to have ability for preventing the attachment of some bacteria and barnacles. In this study, the antifouling ability of zosteric acid during the early stages of fouling was evaluated using attachment studies of fresh water bacteria. Simultaneously, various methods were sought for incorporating zosteric acid into silicone to prolong the release of the compound. The main results from this study were that zosteric acid exhibited anti-bacterial attachment regardless of whether it dispersed in water or incorporated into a coating. In addition, the release rate of zosteric acid from the incorporated coatings, particularly those where zosteric acid was uniformly dispersed with aggregates size of 4 microm or less, was orders of magnitude slower than those of previous reports. The release results indicate that the service life of our coatings could be far extended even with a small amount of zosteric acid incorporated.