Abstract
Clofazimine (CLZ) is an effective antibiotic used against a wide spectrum of Gram-positive bacteria and leprosy. One of its main drawbacks is its poor solubility in water. Silica based materials are used as drug delivery carriers that can increase the solubility of different hydrophobic drugs. Here, we studied how the properties of the silica framework of the mesoporous materials SBA-15, MCM-41, Al-MCM-41, and zeolites NaX, NaY, and HY affect the loading, stability, and distribution of encapsulated CLZ. Time-correlated single-photon counting (TCSPC) and fluorescence lifetime imaging microscopy (FLIM) experiments show the presence of neutral and protonated CLZ (1.3–3.8 ns) and weakly interacting aggregates (0.4–0.9 ns), along with H- and J-type aggregates (<0.1 ns). For the mesoporous and HY zeolite composites, the relative contribution to the overall emission spectra from H-type aggregates is low (<10%), while for the J-type aggregates it becomes higher (~30%). For NaX and NaY the former increased whereas the latter decreased. Although the CLZ@mesoporous composites show higher loading compared to the CLZ@zeolites ones, the behavior of CLZ is not uniform and its dynamics are more heterogeneous across different single mesoporous particles. These results may have implication in the design of silica-based drug carriers for better loading and release mechanisms of hydrophobic drugs.
Highlights
The increase in resistance to antibiotics presents new challenges to fight bacterial infections [1,2,3]
We studied the effect of the structural properties of silica-based hosts on the interactions and dynamics of encapsulated CLZ
In all the materials we observed the protonation of CLZ, its neutral form and aggregates formation. This results in a rich dynamical behavior reflected in a multiexponential emission decays with lifetime components associated with aggregates (0.1 ns), weakly interacting aggregates (0.4–0.9 ns), and neutral and protonated CLZ (1.3–3.8 ns)
Summary
The increase in resistance to antibiotics presents new challenges to fight bacterial infections [1,2,3]. The use of nanocarrier-based drug delivery systems improves the solubility and bioavailability of many drugs [4]. In this way, these systems are capable of releasing the required amount of antibiotic while maintaining its effectiveness, helping to reduce the risk of developing resistance. The nanoconfinement effect exerted by mesoporous silica materials can stabilize the loaded drug in its amorphous state [13], which grants greater molecular motion and enhanced thermodynamic properties, compared to its crystalline state, and provides higher apparent solubility and dissolution rate [14]. Additiroenleaalsley., they are chemically and thermally stable, making them suitable materials for drug deliverzyeoaliptSepisli,lcihaca-abvtaeisobenedse.mn ueTsshoepdeotMrooeuSnsPcmsapahstuaelvraieatelsba,enseduncdheslauisvcemcreedssrsoufpugoslrl[yo1u5us–2sse2il]di.cTathopeassreotimlculaebtseil(riMizaelSsPCpsr)Le, sZMenCatMnhdi-g4h1im,paopnrrdeove its delivervyoliunmseim, laurlgaetesdurgfaacsetrairceafl, uaniddst,utnheuasbloebptoarienidnigameeffteercttihvaet iasnttriamnsilcartoedbitaol hciognhcleonatdriantgiocnapsaicnitiyn. fected macropAhdadgiteiosn[a1l4ly,2, 3th,2e4y].arAedcdheitmioicnaalllysatundditehsehrmavalelyshstoawblen, tmhaaktitnhgetMhemSPssucitaanblbeembaitoecrioamls pfoartidbrluegvessels for drudgeldiveelriyvearpyp,lwicaitihonsst.abThlee aMnSdPds uhraavbelebeeenncsaupcscueslsaftuilolyn uosfetdhetodsroulugbsil[i2z5e–C2L8Z]. aInda irmecperonvtestiutsdy, we reporteddeloivnerhyoiwn stimheulsauterdfagcaestprricofplueirdtise, sthoufsMobStaPisni(nhgyedffreocptihveobanictiamnicdrohbyiadlrcoopnhceilnitcr,awtioinths i1n%inafencdted5% w/w of silanmoal cgrroopuhpagse, sre[1s4p,e23c,t2iv4]e.lAy)ddaffitieocntatlhsetuldoiaeds ihnagv,edsihsotrwibnuthtiaotnt,haenMdSrPeslecaansebeofbCioLcoZmipnawtibaletevreasstedlsifferent pHs [23fo]r. dWruegodbesleivrvereyd, wthitaht stthaeblaemanodudnutroafblseileanncoalpgsurloautipons mofothdeifiderusgtshe[2t5y–p28e].aInnda srterceenngt tshtuodfy,mwoelecular interacrotefiposonirlsaten(dColoLngZrho–ouCwpLstZ,heraessnupdrefcaCtcieLvepZlry–o)spiaelfrifcteiaecstfrotahf meMSleoPwasdo(ihrnkygd),,rdociapsuhtrosibbinuicgtiaoannd,hhaigynhddreorrepllheoiaalsidce,iwnofgithC%L1,%Zhaiingnhdwe5ar%taewrffi/awnt ity for aggregdaitfefefroenrmt paHtiso[n23, ]a.nWdesolboswerevredretlheaatstehewaimthoiunntthoef hsiyladnrool pgrhooubpiscmMoSdPifise,swthheetryeptehaendamstroeunngtthooffsilanol groupsmisolleocwulearr.interactions (CLZ–CLZ and CLZ–silica framework), causing a higher loading %, higher
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