of the many porous 
 materials being developed for sustained release 
 drug delivery systems , electrochemically etched porous silicon ( psi ) is an attractive candidate 
 because of its highly tunable nanostructure ( micro- to macroporous ) , 
 chemically modifiable surface , biocompatibility , and biodegradability .
the biodegradation 
 product of psi is orthosilicic acid [ si(oh)4 ] , which is 
 easily absorbed from the gastrointestinal tract and excreted in the 
 urine .
it has been shown that psi nanoparticles 
 loaded with drugs can be injected intravenously and are degraded in vivo into benign products excreted by the kidneys .
however , interaction between the porous 
 matrix and the drug must be carefully considered to design an effective 
 delivery system that provides controlled release of the drug in its 
 active form .
loaded molecules will quickly diffuse out of porous materials 
 because of local concentration gradients unless additional interactions 
 between the porous matrix and drug are generated .
freshly prepared 
 psi contains highly reactive surface si  h species with underlying 
 elemental silicon , both of which are good reducing agents .
for example , the reduction potential of psi is sufficient to reduce , 
 and thereby inactivate , many organic and inorganic drugs such as doxorubicin , daunorubicin , and 
 cisplatin . thus modification of psi is 
 needed to both limit redox degradation of drugs and increase the affinity 
 of the drug for the psi surface .
various electrostatic or hydrophobic 
 interactions , covalent chemistries , or pore capping reactions have been used to create more effective 
 drug delivery systems . here
we describe a new oxidative psi 
 trapping method that is versatile 
 and sufficiently mild to be useful with a range of drugs possessing 
 a wide variety of characteristics ( organic or inorganic , hydrophilic 
 or hydrophobic , neutral or positively charged , and/or redox - active ) . 

the method relies on the dynamic structure of psi and physical changes 
 that occur during its oxidation .
electrochemically etched psi readily 
 oxidizes in aqueous solutions , which generally results 
 in reduction of the pore volume because of swelling of the pore walls 
 as oxygen is incorporated into the silicon skeleton ( scheme 1 ) .
we hypothesized that pore wall swelling could 
 be used to trap a drug within the psi framework , provided the dimensions 
 of the initial pores , the oxidized pores , and the drug are in a suitable 
 size range .
the redox activity of the psi matrix with the drug candidate 
 is an additional constraint : to prevent the drug from being reduced , 
 the silicon skeleton must be oxidized by something other than the 
 drug being trapped .
we reasoned that an oxidant of sufficient kinetic 
 and thermodynamic competency and concentration could be preferentially 
 reduced , leaving the trapped drug unaffected . because water is a relatively 
 weak oxidant , stronger silicon oxidants such as nitrite , peroxide , and dimethyl 
 sulfoxide ( dmso ) are candidates , depending 
 on the characteristics of the drug being loaded .
although it has 
 a good ability to oxidize silicon or si  h surface bonds , when 
 used as a food preservative it actually suppresses oxidation ; in that 
 case , it limits the oxidation of fatty acids by acting as a trap for 
 free radicals derived from oxygen and other reactive oxygen species . 
 this ability of nitrite ion to act as a chemical oxidant for silicon 
 while simultaneously suppressing more deleterious oxidation reactions 
 is a distinctive characteristic of this oxidant in this work .
this leads to a decrease in 
 pore diameter as the porous silicon film ( bottom left ) becomes partially 
 oxidized ( bottom middle ) and then fully oxidized ( bottom left ) . while we have long suspected that silicon oxidation 
 could be used 
 to load drugs within the psi framework , we have never specifically tested or validated that this loading 
 technique actually leads to drug trapping and further that the drug 
 is not degraded by the loading process .
thus , in this study , we tested 
 the redox trapping method using cobinamide , a vitamin b12 analogue that is being developed as a cyanide antidote .
we chose cobinamide because its hydrophilicity , small size , and 
 redox - active cobalt center make it difficult to load into porous matrices 
 in its active oxidized state ; thus , it presented a greater challenge 
 than most drugs , and if the method worked for cobinamide , it would 
 likely work for other drugs .
we compared cobinamide to rhodamine b , 
 a cationic organic dye with limited redox activity , to prove that 
 cobinamide s redox activity was not involved in the oxidation 
 trapping mechanism .
the distinctive uv  visible absorbance spectra 
 of cobinamide and rhodamine b provided for quick and easy detection 
 and redox state assessment .
boron - doped p - type si wafers ( 110 , 
 0.011 , or 0.030.05  cm resistivity , 100 
 orientation ) were obtained from international wafer service , inc . 

aqueous hydrofluoric acid ( 48% aqueous ) , dimethyl sulfoxide , hydrogen 
 peroxide ( 30% aqueous ) , hydrochloric acid ( 1 m ) , and sodium hydroxide 
 ( all acs grade ) were purchased from fisher scientific .
phosphate - buffered 
 saline ( 1 , ph 7.4 ) was purchased from mediatech , inc .
pure aquohydroxocobinamide was produced by base hydrolysis of hydroxocobalamin 
 ( purchased from sigma - aldrich ) .
porous silicon 
 ( psi ) films were prepared by anodic electrochemical etching of polished 
 si wafers .
a teflon etch cell was used that exposed 8 cm of the si wafer to a 1:1 ( v / v ) 48% aqueous hf / ethanol mixture .
samples 
 were etched at a constant current density of 32 ma / cm for 
 1200 , 600 , and 430 s for samples 13 , respectively . 

the psi films were removed from the crystalline silicon substrate 
 by a current pulse of 5 ma / cm for 50 s in a solution of 
 3.3% aqueous hf in ethanol .
the free - standing psi films were rinsed 
 with ethanol and dried in vacuo . dried psi films ( 10 
 mg )
were immersed in 1 ml of 25 mm sodium nitrite ( ph adjusted to 
 5 with hcl ) within a glass vial and fractured into microparticles 
 by ultrasonication for 30 min .
the mixture was maintained at room 
 temperature for 24 h to allow further oxidation of the particles , 
 and the particles were washed three times each with water and ethanol 
 by centrifugation and dried in vacuo at 60 c 
 for 2 h. the resulting oxidized particles were added to 1 ml of 5 
 mm cobinamide or rhodamine b in deionized water ( ph adjusted to 5 
 with hcl ) and agitated for 16 h at room temperature .
the cobinamide- 
 or rhodamine b - loaded particles were then washed three times each 
 with water and ethanol by centrifugation and dried in vacuo . a 1 ml 
 solution of 5 mm cobinamide or rhodamine b and 25 mm sodium nitrite 
 in water (
ph adjusted to 5 with hcl ) was added to 10 mg of 
 dried psi films in a glass vial .
the mixture was exposed to ultrasonication 
 for 30 min to fracture the si films into microparticles and maintained 
 at room temperature for 24 h to allow further oxidation of the particles 
 in the presence of cobinamide or rhodamine b. the particles were washed 
 three times each with water and ethanol by centrifugation and dried in vacuo at 60 c for 2 h. a scanning 
 electron microscope ( fei xl30 ) was used to obtain cross - sectional 
 images of the psi samples .
attenuated total reflectance fourier transform 
 infrared ( atr - ftir ) spectra were recorded using a thermo scientific 
 nicolet 6700 ftir instrument with a smart itr diamond atr fixture . 

raman spectra were recorded using a renishaw invia raman microscope 
 with a 100 mw , 532 nm laser excitation source .
desorption 
 isotherms were acquired on the freshly etched materials at 77 k on 
 a micromeritics asap 2020 instrument .
thin film optical interference 
 spectra of the porous si samples were recorded in a 180 reflection 
 configuration using an unpolarized tungsten light and an ocean optics 
 4000 ccd spectrometer fitted with a bifurcated fiber - optic cable . 

porous si 
 microparticles loaded with cobinamide or rhodamine b were immersed 
 in 1 ml of either deionized water or aqueous phosphate - buffered saline 
 ( ph 7.4 ) at a particle concentration of 100 g / ml and agitated 
 at room temperature .
the supernatant containing released cobinamide 
 or rhodamine b was collected at set times ( 2 , 8 , 24 , 48 , 72 , 96 , and 
 120 h ) and replaced with fresh water or buffer .
concentrations of 
 released cobinamide were determined by adding excess potassium cyanide 
 to the solution to convert cobinamide to the dicyano form and then 
 measuring the absorbance value at 370 nm (  = 30000 m cm ) .
concentrations of released rhodamine b 
 were determined by the absorbance at 544 nm (  = 106000 m cm ) .
in this study , 
 we were interested in determining how the different porous silicon 
 morphologies generated from silicon wafers with different resistivities 
 ( under similar reaction conditions ) would affect oxidation of the 
 different silicon structures and how those differences would affect 
 the loading and subsequent release of cobinamide from the silicon 
 matrix .
porous silicon films were prepared from single - crystal silicon 
 100 wafers with three different resistivities : 1.20 , 
 0.65 , and 0.05  cm ( samples 13 , respectively ) . 

the silicon wafers were subjected to anodic electrochemical etching 
 in a 1:1 ( v / v ) aqueous 48% hydrofluoric acid / ethanol electrolyte solution . 

a constant current density of 32 ma / cm was used to prepare 
 all three samples , but the etch time was varied so that the thickness 
 of each psi sample was 10 m .
we used the spectroscopic 
 liquid infiltration method ( slim ) to 
 determine the thickness and total open porosity of the etched films 
 and found average open porosities of 60% for samples 1 and 2 and 40% for sample 3 .
these measurements 
 were confirmed by cross - sectional scanning electron microscopy ( figure 
 s1 of the supporting information ) and gravimetric 
 analysis .
the nanostructure of the pores was characterized using nitrogen 
 adsorption  desorption analysis , with the resulting isotherms 
 exhibiting type iv hysteresis loops , typical of mesoporous materials 
 ( figure 1 ) .
porous silicon films were prepared 
 with different pore morphologies to systematically study the influence 
 of pore size on loading and subsequent release of cobinamide from 
 the silicon matrix . the measured brunauer 
teller 
 ( bet ) surface areas of the samples were 
 548 , 482 , and 299 m / g for samples 13 , respectively .
as expected , the pore size increased as the concentration 
 of boron dopant increased for samples 13 as determined 
 by the mean barrett 
halenda ( bjh ) pore diameters of 3.6 , 4.7 , and 5.6 nm , respectively .
nitrogen 
 adsorption  desorption isotherms for porous silicon 
 particles prepared from p - type silicon wafers with resistivities of 
 1.20 , 0.65 , and 0.05  cm for 13 , respectively . 

the adsorption and desorption branches of the isotherms are shown 
 as filled and empty circles , respectively .
the surface chemistry of psi plays a large role in the adsorption 
 of drugs within the porous matrix .
therefore , we first studied the 
 interaction between cobinamide and the psi surface of samples 13 using fourier transform infrared ( ftir ) spectroscopy 
 ( figure 2 and figures s2 and s3 of the supporting information ) . the presence of silicon 
 hydride species on the surface of freshly prepared psi was confirmed 
 by ftir signals assigned to si  h vibrations , at 2108 and 2084 
 cm ( sih2 and sih stretching 
 modes , respectively ) .
to study the initial reaction of cobinamide 
 with the surface of the silicon matrix , ftir spectra of the psi samples 
 were monitored after exposure to aqueous solutions ( ph adjusted to 
 5 with hcl ) with and without cobinamide for 2 h. the ftir spectrum 
 of the cobinamide - exposed sample ( figure 2c ) 
 has an amide stretching frequency at 1660 cm , 
 which is characteristic of free cobinamide [ ftir of free cobinamide 
 ( figure s4 of the supporting information ) ] and absent in a control sample exposed to deionized water ( figure 2b ) . because the samples were thoroughly washed and 
 dried before ftir analysis , the presence of the cobinamide peaks in 
 the spectrum confirms loading of cobinamide in all three psi samples 
 ( 13 ) .
a broad silicon oxide band ( 1100 
 cm ) , along with peaks assigned to oxsi - hy species 
 ( 22002250 cm ) , was also present in both 
 the water- and cobinamide - treated samples .
the height of the silicon 
 oxide band compared to those of the oxsi - hy bands was larger in the 
 cobinamide - exposed sample than in the water - exposed sample .
in addition , 
 the magnitudes of the si  h vibrational bands decreased only 
 slightly for the sample exposed to water alone , while the cobinamide - exposed 
 sample displayed a complete loss of the si 
these 
 findings suggest that the rate of silicon oxidation was increased 
 in the presence of cobinamide .
fourier transform infrared ( ftir ) spectra 
 of a freshly etched porous 
 silicon sample of 2 ( bottom ) , 2 exposed 
 to water ( middle ) , or an aqueous cobinamide solution ( top ) for 2 h. 
 the baselines of the middle and top spectra are offset from the x - axis for comparison .
the redox interaction between cobinamide and the silicon 
 matrix 
 was investigated further using visible reflectance and absorbance 
 spectroscopy .
the optical reflectance spectrum of psi was used to 
 monitor the rate of silicon oxidation in the presence of cobinamide , 
 while the absorbance spectrum of cobinamide was used to determine 
 whether any redox degradation of cobinamide had occurred .
first , silicon 
 oxidation was analyzed by monitoring changes in the optical reflectance 
 spectrum over time of psi sample 2 exposed to cobinamide . 

the fourier transform of these reflectance spectra gave values of 
 2nl , or an effective optical thickness of the psi 
 film .
a value of 2nl can be used to assess how the refractive index ( n ) of the material changes over time [ assuming any changes in sample 
 thickness ( l ) are negligible ] . exposing psi to aqueous 

cobinamide caused a steady decrease in the value of 2nl over time , which can be attributed to a decrease in the refractive 
 index of the sample due to the conversion of si ( nd = 3.8 ) to sio2 ( nd = 1.54 ) ( figure 3 ) .
the absorbance spectrum of the cobinamide solution 
 after it had been exposed to psi for 2 h revealed significant changes 
 compared to that of the original cobinamide solution ( figure 4a ) .
the cobalt center of cobinamide was in the co oxidation state initially ; however , the appearance of new 
 absorption peaks at 315 and 470 nm suggested the co center 
 was reduced to co by the psi .
the absorbance of the cobinamide 
 supernatant obtained after the sample had been exposed to psi for 
 24 h revealed a complete loss of the lowest - energy absorption band 
 leaving only a weak , ill - defined absorption spectrum at wavelengths 
 of < 400 nm . such changes suggest substantial alterations , if not 
 complete loss of the cobalt  corrin ring coordination . to protect the loaded cobinamide from redox degradation , the effect 
 of added oxidants peroxide , nitrite , and dmso was evaluated . in these 
 experiments ,
the oxidant was introduced into the cobinamide solution 
 prior to the addition of the psi sample , so both cobinamide and the 
 oxidant were present in the solution during drug loading .
we found 
 that cobinamide was unstable in the peroxide and dmso solutions but 
 was stable in nitrous acid generated from an acidic sodium nitrite 
 solution [ 25 mm nano2 ( ph 5 ) ] ( eq 1).1the shift in the 2nl value 
 measured for psi samples exposed to cobinamide dissolved in the acidic 
 nitrite solution decreased much more rapidly compared to the shift 
 in 2nl observed upon exposure to cobinamide without 
 nitrite present .
experimental optical response vs time showing the oxidation 
 of 
 psi sample 2 upon exposure to aqueous cobinamide solutions 
 with (  ) or without (  ) nitrite present .
the effective 
 optical thickness ( 2nl , where n is 
 the average refractive index and l is the total thickness 
 of the sample ) was obtained from the fast fourier transform of the 
 optical reflectance spectra of both samples obtained at each time 
 point .
the quantity 2nl ( % ) is defined as 
 ( 2nl  2nl0)/2nl0  100% , where 2nl0 is the value of 2nl measured immediately 
 after introduction of the solutions . in addition , when cobinamide was loaded into the acidic nitrite 
 solution , no change occurred in the relative height or shape of the 
 peaks observed in the solution absorbance spectrum of cobinamide after 
 exposure to psi for 2 or 24 h ( figure 4b ) . 
 instead , only the overall intensity of the spectrum decreased because 
 of the decreased concentration of free cobinamide in solution , as 
 it became trapped within the psi matrix .
the reflectance and absorbance 
 data both suggest that psi preferentially reduced the nitrite , thus 
 protecting cobinamide from redox degradation . to confirm that 
 cobinamide trapped within the psi matrix was indeed 
 protected by the acidic nitrite solution , loaded samples were exposed 
 to sodium hydroxide ( ph 9 ) to dissolve the porous matrix and release 
 the trapped cobinamide .
the absorbance spectra of the released cobinamide 
 loaded in samples 1 and 2 were unchanged 
 compared to the spectrum of preloaded cobinamide , whereas the absorbance 
 spectrum of sample 3 showed signs of redox degradation 
 of the released cobinamide .
 visible absorbance spectra of cobinamide 
 solutions without 
 ( a ) or with ( b ) added nitrite .
absorbance spectra of solutions were 
 recorded before they were exposed to psi particles (  ) , and 
 absorbance spectra of the supernatants were recorded after periods 
 of psi particle exposure of 2 ( --- ) or 24 h (  ) .
therefore , raman spectroscopy 
 was used to elucidate the difference 
 in cobinamide protection between silicon sample 3 ( derived 
 from the more highly doped p - type si ) and samples 1 and 2 .
the raman spectra of samples 1 and 2 contained peaks identical to those in the spectrum of unloaded cobinamide , 
 with no evidence of elemental ( i.e. , unoxidized ) silicon , whereas 
 the spectrum of sample 3 had an additional peak at 520 
 cm assigned to the si 
thus , while the silicon matrices of samples 1 and 2 became fully oxidized , some unoxidized 
 silicon remained after the oxidation trapping of cobinamide in sample 3 .
once a certain thickness of silicon oxide had 
 formed on the pore surface , the room - temperature oxidation process 
 was expected to slow considerably . thus , the pore walls of samples 1 and 2 were sufficiently thin to allow complete 
 oxidation of the si skeleton .
the unoxidized silicon remaining in 
 sample 3 after oxidative loading most likely became exposed 
 during the dissolution of the psi matrix .
this exposed elemental silicon 
 was then able to interact with loaded cobinamide , resulting in the 
 reductive degradation of the drug .
raman spectra of preloaded cobinamide 
 ( free cbi ) and cobinamide - loaded 
 psi particles prepared from p - type silicon wafers with resistivities 
 of 1.20 ( 1-cbi ) , 0.65 ( 2-cbi ) , and 0.05 
 ( 3-cbi )  cm via oxidative trapping of cobinamide 
 with aqueous nitrite solutions ( oxtrap ) .
two different loading methods were compared 
 to determine which provided a higher loading efficiency and more sustained 
 release of cobinamide . for these studies ,
acidic nitrite solutions 
 were used with psi samples 1 and 2 to avoid 
 the redox degradation of cobinamide associated with sample 3 . for the oxidative trapping method ( oxtrap ) , cobinamide was dissolved 
 in an acidic nitrite solution , and the solution was added to freshly 
 etched psi films ; the mixture was ultrasonicated for 30 min to form 
 microparticles and maintained at room temperature for 24 h to complete 
 the oxidation process . for the postoxidation loading method ( postox ) , 
 the psi films were also maintained in the presence of the nitrite 
 oxidizing agent during the 30 min ultrasonication and 24 h oxidation 
 periods , but cobinamide was added to the particles after the 24 h 
 oxidation step .
optical microscope images of the loaded microparticles 
 ( figure 6 ) revealed that the average size of 
 the microparticles was very similar for the two types of postox samples 
 studied ( 21  5 m for 1 and 22  6 m 
 for 2 ) .
bright field optical microscope images of microparticles 
 prepared 
 via the oxidation trapping ( oxtrap , top ) and postoxidation ( postox , 
 bottom ) methods of loading cobinamide .
the psi microparticles were 
 prepared via a 30 min ultrasonication of psi films of sample type 1 ( left ) and 2 ( right ) .
likewise , ultrasonication of either sample 1 or 2 subjected to the oxtrap method yielded particles 
 with similar 
 sizes ( 46  14 m for 1 and 48  14 m 
 for 2 ) .
however , the particles prepared using oxtrap 
 were significantly larger than those prepared using postox for both 1 and 2 . presumably , the simultaneous cobinamide 
 loading and matrix oxidation that occur with the oxtrap method generate 
 a stronger , composite particle that is not as easily fractured by 
 ultrasound energy .
the cobinamide loading efficiency was measured 
 by extracting the 
 loaded cobinamide from the porous si microparticle matrix via treatment 
 with a sodium hydroxide solution ( ph 9 ) .
the basic solution dissolved 
 the si and sio2 components of the microparticle , releasing 
 the drug payload into solution .
we quantified the cobinamide by converting 
 it into the dicyano form ( by adding excess potassium cyanide ) and 
 measuring the optical absorbance at 370 nm (  = 30000 m cm ) .
the average cobinamide loadings 
 were 20  8 and 86  10 g of cobinamide / mg of si 
 for sample 1 and 74  6 and 112  6 g 
 of cobinamide / mg of si for sample 2 for the postox and 
 oxtrap particles , respectively .
thus , for both samples 1 and 2 , the oxtrap method yielded greater cobinamide 
 loading than the postox method , with sample type 2 showing 
 the largest relative increase ( 1.54-fold increased mass loading 
 of drug , relative to that of the postox method ) .
the increased cobinamide 
 loading seen with the microparticles of sample 2 is attributed 
 to the pore size ( 4.7 nm ) being larger than that of sample 1 ( 3.6 nm ) .
the reduction in the average pore size upon oxidation 
 of the silicon matrix is expected to show a more pronounced effect 
 on the efficiency of drug loading as the pore size approaches the 
 diameter of the drug payload , and this is observed in the data . when 
 introduced before oxidation in the oxtrap method
, cobinamide can more 
 freely penetrate the pores , and the silicon oxide can then grow around 
 the cobinamide molecules .
we next tested the retention of cobinamide 
 within the oxidized 
 silicon matrix for the different microparticle formulations .
in pure 
 water , the rate of silicon dissolution is relatively slow , which is 
 expected to delay the release of cobinamide trapped within the silicon 
 oxide matrix . if cobinamide is not physically trapped , it will be 
 free to diffuse out of the pores even if the silicon matrix has not 
 degraded .
consistent with these arguments , the release of cobinamide 
 from the postox particles was significantly more rapid than from the 
 oxtrap particles for both sample types 1 and 2 ( figure 7a ) , with 50% of the loaded drug 
 released within 3 h for postox versus 3 days for oxtrap formulations . 

this confirms that oxidation of the psi skeleton in the presence of 
 cobinamide will effectively trap the drug in the pores and that this 
 process increases the level of retention of cobinamide in the resulting 
 microparticles .
we observed no significant difference in the cobinamide 
 release rate between samples 1 and 2 for 
 the postox - loaded samples and only a slight difference for the oxtrap 
 particles .
the slight reduction in the release rate for sample 2 could be due to the slightly larger amount of cobinamide 
 loaded in the particles , which may act to shield the silicon matrix 
 from water dissolution .
release of cobinamide into water ( a ) or aqueous 
 phosphate - buffered 
 saline ( b ) from oxidized psi particles 1 ( circles ) and 2 ( squares ) loaded with cobinamide via the postoxidation ( postox , 
 empty symbols ) or oxidation trapping ( oxtrap , filled symbols ) method . 

the data were averaged from three samples , and the error bars indicate 
 the standard deviation .
the release of cobinamide from the microparticles was also 
 tested 
 in phosphate - buffered saline ( pbs ) , a more physiologically relevant 
 solution ( figure 7b ) .
the psi matrix degraded 
 more quickly in pbs than in water , although as with pure water , the 
 release profile showed a smaller rate of cobinamide release for the 
 oxtrap than for the postox microparticles for both samples 1 and 2 .
however , the difference in release rates was 
 less pronounced for the pbs experiments than for the water experiments 
 because of the increased rate of dissolution of silicon in pbs . in 
 addition , for a given preparation ( oxtrap or postox ) , we observed 
 no significant difference between the release profiles of sample types 1 and 2 . to determine
if the oxidation 
 trapping method could be used for 
 molecules other than cobinamide , we repeated the loading and release 
 studies of sample type 2 using rhodamine b. we loaded 
 rhodamine b like cobinamide using both the postox and oxtrap methods . 

as for cobinamide , a larger mass loading was achieved with the oxtrap 
 protocol ( 87  5 g of rhodamine b / mg of si ) than with 
 the postox method ( 7  1 g of rhodamine b / mg of si ) .
the 
 release profiles ( in deionized water ) for the delivery of rhodamine 
 b from postox particles showed more sustained release than from postox 
 particles ( figure 8) .
the data confirmed that 
 the oxtrap method is not specific to cobinamide , providing larger 
 mass loading and more effective trapping for both types of molecules .
release 
 of rhodamine b into water from type 2 oxidized 
 porous silicon particles loaded with rhodamine b via the postoxidation 
 [ postox (  ) ] or oxidation trapping [ oxtrap (  ) ] method . 

the data are the means of three samples , and the error bars indicate 
 the standard deviation .
this study focused on the ability of porous 
 si to shrink its pore 
 dimensions upon mild oxidation of the porous skeleton , to enhance 
 the loading capacity and extend the duration of release of small hydrophilic 
 drugs . via oxidation of the silicon matrix in the presence of the 
 molecular payload ( oxtrap ) ,
the molecule was more effectively trapped 
 than it was after simple diffusional loading into a preformed oxide 
 matrix .
it was found that the pore and molecule size is a critical 
 parameter in this process ; the pore and molecule must be appropriately 
 matched to allow the molecule to diffuse into the unoxidized pore 
 and not diffuse out of the oxidized pore .
for cobinamide , the optimal 
 unoxidized pore diameter was between 3.6 and 4.7 nm .
for redox - active 
 drugs , the pore wall thickness is an additional important factor . 

we found that material with smaller pore diameters ( and thus thinner 
 pore walls ) could be completely oxidized to sio2 under 
 mild ( room temperature , aqueous nitrite ) conditions , whereas material 
 with thicker pore walls retained elemental silicon within the porous 
 skeleton .
this residual silicon then reacted with and degraded the 
 cobinamide model drug under long - term aqueous release conditions . 

in addition , we showed that aqueous acidic nitrite ( no ) acts as a mild oxidant that does not degrade the model drugs but 
 is sufficiently reactive to oxidize the si skeleton , outcompeting 
 the reduction of cobinamide by si and thus preserving the activity 
 of the molecule .
we found that porous si samples prepared in a 1:1 
 ( v / v ) hf / ethanol solution from p - type silicon wafers with a resistivity 
 of 0.65  cm possess pore walls sufficiently thin to 
 become fully oxidized , whereas the pore walls in porous si made from 
 silicon with a resistivity of < 0.5  cm are too thick and 
 do not become fully oxidized under the oxtrap reaction conditions . 

this approach may be generally applicable to a wider range of drugs , 
 including more sensitive protein and oligonucleotide therapeutics .
 an 
 approach for the preparation of an oxidized porous silicon microparticle 
 drug delivery system that can provide efficient trapping and sustained 
 release of various drugs is reported . 
 the method uses the contraction 
 of porous silicon s mesopores , which occurs during oxidation 
 of the silicon matrix , to increase the loading and retention of drugs 
 within the particles . 
 first , a porous si ( psi ) film is prepared by 
 electrochemical etching of p - type silicon with a resistivity of > 0.65 
  cm in a 1:1 ( v / v ) hf / ethanol electrolyte solution . under these 
 conditions , 
 the pore walls are sufficiently thin to allow for complete 
 oxidation of the silicon skeleton under mild conditions . 
 the psi film 
 is then soaked in an aqueous solution containing the drug ( cobinamide 
 or rhodamine b test molecules were used in this study ) and sodium 
 nitrite . 
 oxidation of the porous host by nitrite results in a shrinking 
 of the pore openings , which physically traps the drug in the porous 
 matrix . 
 the film is subsequently fractured by ultrasonication into 
 microparticles . upon comparison with commonly used oxidizing agents 
 for psi such as water , peroxide , and dimethyl sulfoxide , nitrite is 
 kinetically and thermodynamically sufficient to oxidize the pore walls 
 of the psi matrix , precluding reductive ( by si ) or oxidative ( by nitrite ) 
 degradation of the drug payload . 
 the drug loading efficiency is significantly 
 increased ( by up to 10-fold ) , and the release rate is significantly 
 prolonged ( by 20-fold ) relative to control samples in which the drug 
 is loaded by infiltration of psi particles postoxidation . 
 we find 
 that it is important that the silicon skeleton be completely oxidized 
 to ensure the drug is not reduced or degraded by contact with elemental 
 silicon during the particle dissolution  drug release phase . 
Introduction
Experimental
Section
Results and Discussion
Conclusions