Preparation and characterisation of self-emulsifying drug delivery system (SEDDS) for enhancing oral bioavailability of metformin hydrochloride using hydrophobic ion pairing complexation.

AIM: The aim of this study was preparation of a self-emulsifying drug delivery system (SEEDS) containing metformin hydrochloride. METHODS: Hydrophobic ion paired complexes were prepared by electrostatic interaction between metformin and sodium lauryl sulphate (SLS). The nanodroplets were optimised using two-level full factorial methodology and their morphology were examined. In vitro release of metformin from SEDDS was evaluated in simulated gastric and intestinal fluids. Finally, the ex-vivo efficacy of the optimised formulation in enhancing the intestinal permeability of metformin was evaluated using non-everted intestinal sac. RESULTS: The data revealed that in weight ratio 1:4(metformin: SLS), the highest recovery was achieved. The physico-chemical properties of the optimised nano-droplets including size, polydispersity index (PdI), zeta potential, and loading efficiency (%) were 192.33 ± 9.9 nm, 0.275 ± 0.051; -1.52 mV, and 93.75 ± 0.77% (w/w), respectively. CONCLUSIONS: The data obtained from the intestinal transport study demonstrated that SEDDS can significantly enhance the oral permeability of the compound.

Nano optical and electrochemical sensors and biosensors for detection of narrow therapeutic index drugs.

For the first time, a comprehensive review is presented on the quantitative determination of narrow therapeutic index drugs (NTIDs) by nano optical and electrochemical sensors and biosensors. NTIDs have a narrow index between their effective doses and those at which they produce adverse toxic effects. Therefore, accurate determination of these drugs is very important for clinicians to provide a clear judgment about drug therapy for patients. Routine analytical techniques have limitations such as being expensive, laborious, and time-consuming, and need a skilled user and therefore  the nano/(bio)sensing technology leads to high interest.

Hydrophobic ion pairing with cationic derivatives of α-, ß-, and γ-cyclodextrin as a novel approach for development of a self-nano-emulsifying drug delivery system (SNEDDS) for oral delivery of heparin.

To enhance the oral bioavailability of heparin, a self-nano-emulsifying drug delivery system (SNEDDS) was developed using hydrophobic ion-pairing with cationic polymers of α-, ß-, and γ-cyclodextrins (CPCDs). Hydrophobic ion paired complexes were formed, and the recovery of heparin was determined in n-hexane and isopropyl myristate (IPM). The SNEDDSs were prepared and were optimized using D-optimal response surface methodology (RSM). The determination of the recovery of complexes in IPM revealed that in cationic α-cyclodextrin, the highest recovery was achieved at the heparin: CPCD weight ratio of 1:0.5. However, in cationic ß-cyclodextrin the highest recovery was obtained at the weight ratio of 1:4. Similar to CPßCD, for ealed that in c the highest recovery was obtained at 1:4 weight ratio. The size of optimized nano-droplets was found to be 127.00 ± 4.1, 184.00 ± 6.43, and 216.00 ± 5.43 nm; polydispersity index (PdI) values were reported as 0.372 ± 0.005, 0.163 ± 0.008, 0.236 ± 0.003; and calculated loading efficiency (LE%) were 84.60 ± 3.62, 91.06 ± 2.49, and 92.81 ± 0.70% for SNEDDS preparations incorporating cationic derivatives of α-, ß-, and γ-cyclodextrin, respectively. The in vitro release study revealed that SNEDDS preparations containing cationic γ-cyclodextrin posed the slowest release rate. Data achieved from cellular uptake study showed that the SNEDDS containing α-cyclodextrin had the highest cumulative uptake percentage after 6 h post-exposure; same results were obtained in the intestinal transport study demonstrating SNEDDS containing α-cyclodextrin posed the highest transport efficiency with Papp of 24.85 × 10-r ± 1.06 × 10-± cm.s-m.

Pharmacokinetics and brain distribution studies of perphenazine-loaded solid lipid nanoparticles.

BACKGROUND: Perphenazine (PPZ) is a typical antipsychotic that is mainly administrated for the treatment of schizophrenia. Due to its highly lipophilic nature and extensive hepatic first-pass metabolism, its oral bioavailability is low (40%). OBJECTIVE: The novel nanocarriers like solid lipid nanoparticles (SLN) have been reported to be highly effective for improving the therapeutic effect of drugs. Therefore the main scope of the present investigation was the evaluation of in vivo characteristics of PPZ-SLN in terms of pharmacokinetic parameters and brain distribution. METHODS: The PPZ-SLN was prepared by the solvent-emulsification and evaporation method. The storage stability of PPZ-SLN and empty SLN powders was studied for 3 months. In vivo pharmacokinetic studies and brain distribution evaluations were performed following a single oral dose administration of PPZ and PPZ-SLN suspensions on male Wistar rats. An HPLC method was established and validated for the quantitative determination of PPZ in plasma and brain samples. RESULTS: The storage stability studies revealed the good storage stability of the both PPZ-SLN and empty SLN at 4 °C. Compared to PPZ suspension, the relative bioavailability and the brain distribution of PPZ-SLN were increased up to 2-fold and 16-fold, respectively. Mean residence time (MRT) and half-life (t1/2) of PPZ-SLN were significantly (p value < 0.01) increased in both plasma and brain homogenate compared to PPZ suspension. CONCLUSION: The significant improvement in the pharmacokinetic properties of PPZ following one oral dose indicates that SLN is a promising drug delivery system for PPZ and shows a high potential for successful brain delivery of this antipsychotic.

Preparation, statistical optimization, in vitro characterization, and in vivo pharmacological evaluation of solid lipid nanoparticles encapsulating propolis flavonoids: a novel treatment for skin edema.

Propolis is a natural resinous product and exerts anti-inflammatory properties. The aim of this study is formulation and characterization of solid lipid nanoparticles (SLNs) encapsulating propolis flavonoids (PFs), intended for topical treatment of skin edema. The nanoparticles were prepared and statistically optimized using Box-Behnken response surface methodology. The in vitro release profile of the optimized nanoparticles was investigated. Cytotoxicity of nanoparticles on HSF-PI 18 cell line was determined. Permeation and penetration of nanoparticles across the incised skin were measured. Finally, the nanoparticles were incorporated into a pharmaceutical hydrogel formulation and the in vivo efficacy in reduction of skin edema was determined. The size, PdI, zeta potential, entrapment efficiency (EE%) and loading efficiency (LE %) of the optimized nanoparticles were 111.3 ± 19.35 nm, 0.34 ± 0.005, -24.17 ± 3.3 mV, 73.5 ± 0.86%, and 3.2 ± 0.27%, respectively. Data obtained through in vitro release study suggested a burst release followed by a prolonged release behavior up to 24 h post incubation time interval. The prepared SLNs exhibited no cytotoxicity on HSF-PI 18 cell line. Ex vivo permeation and penetration study of nanoparticles across the incised skin showed approximately a 2.5-fold and a 3-fold increase in cumulative amount of transport and cumulative amount of skin penetration, respectively. Finally, in vivo studies in rat models, showed a threefold reduction in volume of the edema in animals treated with SLNs. The obtained data revealed that the prepared SNs entrapping PFs, exert high skin targeting effects, prolonged anti-inflammatory properties and therefore high efficiency in treatment of skin edema.

Preparation and characterization of self nano-emulsifying drug delivery system (SNEDDS) for oral delivery of heparin using hydrophobic complexation by cationic polymer of ß-cyclodextrin.

OBJECTIVE: The aim of this study was the preparation of a self nano-emulsifying drug delivery system (SNEDDS) for oral delivery of heparin. SIGNIFICANCE: Preparation of hydrophobic complexes between heparin as the hydrophilic macromolecule and cationic polymer of ß-cyclodextrin (CPßCD) was considered for preparation of orally administered SNEDDS in which the drug incorporated in internal oil phase of O/W nano-droplets. METHODS: Hydrophobic complexes of heparin-CPßCD were prepared by electrostatic interaction. The lipophilic feature of complexes was characterized by determining their partition co-efficients. SNEDDS prototypes were prepared by mixing liquid paraffin, Tween 80, propylene glycol and ethanol, diluted 1:100 in an aqueous medium. Central composite response surface methodology was applied for statistical optimization. Independent variables were the amount of liquid paraffin and the amount of Tween 80, while responses were size and poly dispersity index (PdI). Optimized SNEDDS were studied morphologically using transmission electron microscopy (TEM). In vitro release of heparin was studied in the simulated gastric and simulated intestinal media. RESULTS: The data revealed that in molar ratio 1:3 (heparin:CPßCD), the n-octanol recovery was maximized and reached 67.6 ± 11.86%. Size, PdI, zeta potential, EE% in gastric medium and EE% in intestinal medium for optimized nano-droplets were reported as 307 ± 30.51 nm, 0.236 ± 0.02, +2.1 ± 0.66 mV, 90.2 ± 0.04 and 96.1 ± 0.73%, respectively. Microscopic images revealed spherical nano-droplets. The obtained data revealed no burst release of heparin from nano-droplets. CONCLUSIONS: The obtained results indicate that SNEDDS could be regarded as a good candidate for oral delivery of heparin as the hydrophilic macromolecule.

Preparation and optimization of N-trimethyl-O-carboxymethyl chitosan nanoparticles for delivery of low-molecular-weight heparin.

The aim of this study was preparation, optimization and in vitro characterization of nanoparticles composed of 6-[O-carboxymethyl]-[N,N,N-trimethyl] (TMCMC) for oral delivery of low-molecular-weight heparin. The chitosan derivative was synthesized. Nanoparticles were prepared using the polyelectrolyte complexation method. Box-Behnken response surface experimental design methodology was used for optimization of nanoparticles. The morphology of nanoparticles was studied using transmission electron microscopy. In vitro release of enoxaparin from nanoparticles was determined under simulated intestinal fluid. The cytotoxicity of nanoparticles on a Caco-2 cell line was determined, and finally the transport of prepared nanoparticles across Caco-2 cell monolayer was defined. Optimized nanoparticles with proper physico-chemical properties were obtained. The size, zeta potential, poly-dispersity index, entrapment efficiency and loading efficiency of nanoparticles were reported as 235 ± 24.3 nm, +18.6 ± 2.57 mV, 0.230 ± 0.03, 76.4 ± 5.43% and 12.6 ± 1.37%, respectively. Morphological studies revealed spherical nanoparticles with no sign of aggregation. In vitro release studies demonstrated that 93.6 ± 1.17% of enoxaparin released from nanoparticles after 600 min of incubation. MTT cell cytotoxicity studies showed no cytotoxicity at 3 h post-incubation, while the study demonstrated concentration-dependent cytotoxicity after 24 h of exposure. The obtained data had shown that the nanoparticles prepared from trimethylcarboxymethyl chitosan may be considered as a good candidate for oral delivery of enoxaparin.

Development and validation of a novel, simple, and accurate spectrophotometric method for the determination of lead in human serum.

The determination of blood lead levels is the most useful indicator of the determination of the amount of lead that is absorbed by the human body. Various methods, like atomic absorption spectroscopy (AAS), have already been used for the detection of lead in biological fluid, but most of these methods are based on complicated, expensive, and highly instructed instruments. In this study, a simple and accurate spectroscopic method for the determination of lead has been developed and applied for the investigation of lead concentration in biological samples. In this study, a silica gel column was used to extract lead and eliminate interfering agents in human serum samples. The column was washed with deionized water. The pH was adjusted to the value of 8.2 using phosphate buffer, and then tartrate and cyanide solutions were added as masking agents. The lead content was extracted into the organic phase containing dithizone as a complexion reagent and the dithizone-Pb(II) complex was formed and approved by visible spectrophotometry at 538 nm. The recovery was found to be 84.6 %. In order to validate the method, a calibration curve involving the use of various concentration levels was calculated and proven to be linear in the range of 0.01-1.5 µg/ml, with an R (2) regression coefficient of 0.9968 by statistical analysis of linear model validation. The largest error % values were found to be -5.80 and +11.6 % for intra-day and inter-day measurements, respectively. The largest RSD % values were calculated to be 6.54 and 12.32 % for intra-day and inter-day measurements, respectively. Further, the limit of detection (LOD) was calculated to be 0.002 µg/ml. The developed method was applied to determine the lead content in the human serum of voluntary miners, and it has been proven that there is no statistically significant difference between the data provided from this novel method and the data obtained from previously studied AAS.

Oral self-nanoemulsifying peptide drug delivery systems: impact of lipase on drug release.

It was the aim of this study to evaluate the impact of lipases on the release behaviour of a peptide drug from oral self-nanoemulsifying drug delivery systems. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate, oleate and dodecylsulphate. The lipophilic character of these complexes was characterised by determining the n-octanol/buffer pH 7.4 partition coefficient. In the following the most hydrophilic complex was incorporated in a likely lipase degradable self-nanoemulsifying drug delivery systems (SNEDDS) formulation containing a triglyceride (olive oil; Pharm.Eur.) and in a likely not lipase degradable SNEDDS containing lipids and surfactants without any ester bonds. After 1:100 dilutions in artificial intestinal fluid (AIF), the lipid droplets were characterised regarding size distribution. With these SNEDDS, drug release studies were performed in AIF with and without lipase. Results showed that the most hydrophobic complex can be formed with deoxycholate in an octreotide:anionic surfactant ratio of 1:5. Even 73.1 ± 8.1% of it could be quantified in the n-octanol phase. SNEDDS containing octreotide | olive oil | cremophor EL | propylene glycol (2|57|38|3) and octreotide | liquid paraffin | Brij 35 | propylene glycol | ethanol (2|66.5|25|5|1.5) showed after dilution in AIF, a mean droplet size of 232 ± 53 nm and 235 ± 50 nm, respectively. Drug release studies showed a sustained release of octreotide out of these formulations for at least 24 h, whereas > 80% of the drug was released within 2 h in the presence of lipase in the case of the triglyceride containing SNEEDS. In contrast the release profile from ester-free SNEDDS was not significantly altered (p < 0.05) due to the addition of lipase providing evidence for the stability of this formulation towards lipases. According to these results, SNEDDS could be identified as a useful tool for sustained oral peptide delivery taking an enzymatic degradation by intestinal lipases into considerations.

Controlled-release drug delivery system based on fluocinolone acetonide-cyclodextrin inclusion complex incorporated in multivesicular liposomes.

Multivesicular liposomes (MVLs) have been widely studied for encapsulation of hydrophilic drugs due to their structural properties and large aqueous inner cavities. In this study, to investigate MVLs and their potential application for incorporation of hydrophobic drugs, new drug delivery system for fluocinolone acetonide (FA), as a lipophilic model drug, was developed combining the advantages of cyclodextrin inclusion complexes (CD-IC) and multivesicular liposomes. FA was complexed with several CDs to form inclusion complex (FA-CD-IC) and then FA-CD-IC was incorporated into MVLs by reverse-phase evaporation method. Physicochemical characterization of drug-CD-IC, at a molar ratio of 1:1 (drug to CD) was studied using 1HNMR, FT-IR, DSC and UV spectroscopy. The influence of various types of CDs on the aqueous solubility of FA, encapsulation efficiency and release profile in MVLs was studied. The results revealed the formation of inclusion complexes between the drug and CDs. Both the CD's type and proportion played an important role in the physicochemical properties of the systems. The inclusion complex of the drug with hydroxypropyl-ß-cyclodextrin exhibited the most appropriate loading and sustained-release profile over prolonged periods. The results reveal the promising potential of MVLs as a stable drug delivery system to release the drug in a sustained manner for the treatment of ocular inflammatory disease.

Development of acid-resistant alginate/trimethyl chitosan nanoparticles containing cationic ß-cyclodextrin polymers for insulin oral delivery.

In this study, the use of trimethylchitosan (TMC), by higher solubility in comparison with chitosan, in alginate/chitosan nanoparticles containing cationic ß-cyclodextrin polymers (CPßCDs) has been studied, with the aim of increasing insulin uptake by nanoparticles. Firstly, TMCs were synthesized by iodomethane, and CPßCDs were synthesized within a one-step polycondensation reaction using choline chloride (CC) and epichlorohydrine (EP). Insulin-CßCDPs complex was prepared by mixing 1:1 portion of insulin and CPßCDs solutions. Then, nanoparticles prepared in a three-step procedure based on the iono-tropic pregelation method. Nanoparticles screened using experimental design and Placket Burman methodology to obtain minimum size and polydispercity index (pdI) and the highest entrapment efficiency (EE). CPßCDs and TMC solution concentration and pH and alginate and calcium chloride solution concentrations are found as the significant parameters on size, PdI, and EE. The nanoparticles with proper physicochemical properties were obtained; the size, PdI, and EE% of optimized nanoparticles were reported as 150.82 ± 21 nm, 0.362 ± 0.036, and 93.2% ± 4.1, respectively. The cumulative insulin release in intestinal condition achieved was 50.2% during 6 h. By SEM imaging, separate, spherical, and nonaggregated nanoparticles were found. In the cytotoxicity studies on Caco-2 cell culture, no significant cytotoxicity was observed in 5 h of incubation, but after 24 h of incubation, viability was decreased to 50% in 0.5 mµ of TMC concentration. Permeability studies across Caco-2 cells had been carried out, and permeability achieved in 240 min was 8.41 ± 0.39%, which shows noticeable increase in comparison with chitosan nanoparticles. Thus, according to the results, the optimized nanoparticles can be used as a new insulin oral delivery system.

Lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan as a new strategy for oral delivery of insulin: in vitro, ex vivo and in vivo characterizations.

OBJECTIVE: The purpose of this research was the development, in vitro, ex vivo and in vivo characterization of lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan. METHODS: Insulin nanoparticles were prepared from methylated N-(4-N,N-dimethylaminobenzyl), methylated N-(4 pyridinyl) and methylated N-(benzyl). Insulin nanoparticles containing non-modified chitosan and also trimethyl chiotsan (TMC) were also prepared as control. The effects of the freeze-drying process on physico-chemical properties of nanoparticles were investigated. The release of insulin from the nanoparticles was studied in vitro. The mechanism of the release of insulin from different types of nanoparticles was determined using curve fitting. The secondary structure of the insulin released from the nanoparticles was analyzed using circular dichroism and the cell cytotoxicity of nanoparticles on a Caco-2 cell line was determined. Ex vivo studies were performed on excised rat jejunum using Frantz diffusion cells. In vivo studies were performed on diabetic male Wistar rats and blood glucose level and insulin serum concentration were determined. RESULTS: Optimized nanoparticles with proper physico-chemical properties were obtained. The lyophilization process was found to cause a decrease in zeta potential and an increase in PdI as well as and a decrease in entrapment efficiency (EE%) and loading efficiency (LE%) but conservation in size of nanoparticles. Atomic force microscopy (AFM) images showed non-aggregated, stable and spherical to sub-spherical nanoparticles. The in vitro release study revealed higher release rates for lyophilized compared to non-lyophilized nanoparticles. Cytotoxicity studies on Caco-2 cells revealed no significant cytotoxicity for prepared nanoparticles after 3-h post-incubation but did show the concentration-dependent cytotoxicity after 24 h. The percentage of cumulative insulin determined from ex vivo studies was significantly higher in nanoparticles prepared from quaternized aromatic derivatives of chitosan. In vivo data showed significantly higher insulin intestinal absorption in nanoparticles prepared from methylated N-(4-N, N-dimethylaminobenzyl) chitosan nanoparticles compared to trimethyl chitosan. CONCLUSION: These data obtained demonstrated that as the result of optimized physico-chemical properties, drug release rate, cytotoxicity profile, ex vivo permeation enhancement and increased in vivo absorption, nanoparticles prepared from N-aryl derivatives of chitosan can be considered as valuable method for the oral delivery of insulin.

Development of a label-free, sensitive gold nanoparticles-poly(adenine) aptasensing platform for colorimetric determination of aflatoxin B1 in corn.

In this work, a sensitive colorimetric bioassay method based on a poly(adenine) aptamer (polyA apt) and gold nanoparticles (AuNPs) was developed for the determination of aflatoxin B1 (AFB1). The polyA apt, adsorbed on the AuNPs, especially can bind to the analyte while deterring non-specific interactions. This nano aptasensor uses cationic polymer poly(diallyl dimethyl ammonium chloride) (PDDA), as an aggregating agent, to aggregate gold nanoparticles. PolyA apt-decorated gold nanoparticles (AuNPs/polyA apt) show resistance to PDDA-induced aggregation and maintains their dispersed state (red color) with the optical absorbance signal at λ = 520 nm. However, in the presence of AFB1 in the assay solution, the specific aptamer reacts with high affinity and folds into its three-dimensional form. Aggregation of AuNPs induced by PDDA caused their optical signal shift to λ = 620 nm (blue color). AFB1 concentration in the bioassay solution determines the amount of optical signal shift. Therefore, optical density ratio in two wavelengths (A620/520) can be used as a sturdy colorimetric signal to detect the concentration of aflatoxin B1. AFB1 was linearly detected between 0.5 and 20 ng mL-1, with a detection limit of 0.09 ng mL-1 (S/N = 3). The fabricated aptasensor was applied to the detection of AFB1 in real corn samples.

Anti-CD44 and EGFR Dual-Targeted Solid Lipid Nanoparticles for Delivery of Doxorubicin to Triple-Negative Breast Cancer Cell Line: Preparation, Statistical Optimization, and In Vitro Characterization.

Background: Despite being more aggressive than other types of breast cancer, there is no suitable treatment for triple-negative breast cancer (TNBC). Here, we designed doxorubicin-containing solid lipid nanoparticles (SLNs) decorated with anti-EGFR/CD44 dual-RNA aptamers, which are overexpressed in TNBC. For more efficiency in the nuclear delivery of doxorubicin, dexamethasone (Dexa) was chemically attached to the surface of nanoparticles. Methods: To prepare the cationic SLNs, 6-lauroxyhexyl BOC-ornithine (LHON) was synthesized and was chemically attached to dexamethasone to form Dexa-LHON complexes. The doxorubicin-containing SLNs were prepared via double emulsification (w/o/w) and the solvent evaporation technique. The preparation of SLNs was statistically optimized using the central composite response surface methodology. Independent factors were the GMS/lecithin concentration ratio and the amount of Tween 80, while responses considered were particle size, polydispersity index, and entrapment efficiency of the nanoparticles. The optimized nanoparticles were studied morphologically using transmission electron microscopy, and in vitro release of doxorubicin from nanoparticles was studied in phosphate-buffered saline. Then, the designated aptamers were attached to the surface of nanoparticles using electrostatic interactions, and their cytotoxicity was assessed in vitro. Results: The size, PDI, zeta potential, EE%, and LE% of the prepared nanoparticles were 101 ± 12.6 nm, 0.341 ± 0.005, +13.6 ± 1.83 mV, 69.98 ± 7.54%, and 10.2 ± 1.06%, respectively. TEM images revealed spherical nanoparticles with no sign of aggregation. In vitro release study exhibited that 96.1 ± 1.97% of doxorubicin was released within 48 h of incubation. The electrostatic attachment of the designated aptamers to the nanoparticles' surface was confirmed by reducing the zeta potential to -15.6 ± 2.07 mV. The in vitro experiments revealed that the SLNs/DOX/Dexa/CD44 or EGFR aptamers were substantially more successful than SLNs/DOX/Dexa at inhibiting cell proliferation. Using the MDA-MB-468 cell line, we discovered that SLN/DOX/Dexa/CD44/EGFR aptamers were more effective than other constructs in inhibiting cell proliferation (p < 0.001). The reduction of cell viability using this construct suggests that targeting numerous proliferation pathways is effective. Conclusion: Overall, the finding of this investigation suggested that SLNs/DOX/Dexa/CD44/EGFR could be a promising new enhanced anticancer delivery system and deserved further preclinical consideration.

The assessment of microencapsulated Lactobacillus plantarum survivability in rose petal jam and the changes in physicochemical, textural and sensorial characteristics of the product during storage.

The present study aimed to develop a probiotic rose petal jam containing microencapsulated L. plantarum. The attributes of L. plantarum microcapsules and bacteria viability in simulated gastrointestinal conditions and jam were assessed. In addition, L. plantarum effects on physicochemical, textural and sensorial properties of jam were studied. The microencapsulation yield, diameter, and zeta potential value of the microcapsules ranged from 90.23 to 92.75%, 14.80-35.02 µm, and - 16.83 to - 14.71 mV, respectively. The microencapsulation process significantly increases the survival of L. plantarum in simulated gastrointestinal tract and jam. In jam samples containing L. plantarum microencapsulated with 2% sodium alginate and 3.5% or 5% Arabic gum and stored for 90 days, the bacterial count was higher than the acceptable level (106 CFU/g). While there was no significant difference (P > 0.05) between physicochemical characteristics of non-probiotic and probiotic jams, taste and overall acceptance scores of microencapsulated probiotic jams were higher. The microencapsulation of L. plantarum in sodium alginate (2%) and Arabic gum (5%) and its inoculation into rose petal jam could yield a new probiotic product with increased health benefits.

A novel label-free colorimetric polyA aptasensing approach based on cationic polymer and silver nanoparticles for detection of tobramycin in milk.

In this study, a novel colorimetric bioassay method was developed for the sensitive determination of tobramycin (TOB). To detect TOB, silver nanoparticles (AgNPs) were decorated with TOB-specific aptamers (apt), and positively charged poly diallyl dimethyl ammonium chloride (PDDA) was used. As long as tobramycin is not present in the assay system, PDDA can coalesce with the aptamer, and AgNPs would remain stable (λmax = 400 nm) in the dispersed system against PDDA-induced aggregation. When TOB is added, aptamer can bind to the compound, which leads to release of PDDA and subsequent aggregation of AgNPs (λmax = 540 nm). This remarkable change, as a colorimetric analytics signal, can be used for quantitative analysis of TOB. TOB can be detected by this highly sensitive colorimetric aptasensor with a limit of detection (LOD) of 70 pM. Furthermore, TOB can be detected with the naked eye at concentrations above 1 nM.

Budesonide-Loaded Hyaluronic Acid Nanoparticles for Targeted Delivery to the Inflamed Intestinal Mucosa in a Rodent Model of Colitis.

The aim of the present study was to investigate the therapeutic potential of budesonide- (BDS-) loaded hyaluronic acid nanoparticles (HANPs) for treatment of inflammatory bowel disease (IBD) using an acute model of colitis in rats. The therapeutic efficacy of BDS-loaded HANPs in comparison with an aqueous suspension of the drug with the same dose (30 µg/kg) was investigated 48 h following induction of colitis by intrarectal administration of acetic acid 4% in rats. Microscopic and histopathologic examinations were conducted in inflamed colonic tissue. Tissue concentration of tumor necrosis factor (TNF)-α was assessed by ELISA assay kit, while the activity of myeloperoxidase (MPO) was measured spectrophotometrically. Results from in vivo evaluations demonstrated that administrations of BDS-HANPs ameliorated the general endoscopic appearance, quite close to the healthy animals with no signs of inflammation and reduced the cellular infiltration, as well as the TNF-α level, and the MPO activity. It was found that delivery by BDS-loaded HANPSs alleviated the induced colitis significantly better than the same dose of the free drug. These data further suggest the potential of HANPs as a targeted drug delivery system to the inflamed colon mucosa.

Preparation, statistical optimization, and in vitro characterization of insulin nanoparticles composed of quaternized aromatic derivatives of chitosan.

The aim of this study was the preparation, optimization, and in vitro characterization of insulin nanoparticles composed of methylated N-(4-N,N-dimethylaminobenzyl), methylated N-(4-pyridinyl), and methylated N-(benzyl) chitosan. Three types of derivatives were synthesized by the Schiff base reaction followed by quaternization. Nanoparticles were prepared by the polyelectrolyte complexation method. Experimental design D-optimal response surface methodology was used for the optimization of the nanoparticles. Independent variables were pH of polymer solution, concentration ratio of polymer/insulin, and also polymer type. Dependent variables include size, zeta potential, polydispersity index (PdI), and entrapment efficiency (EE%). Optimized nanoparticles were studied morphologically by transmission electron microscopy (TEM), and in vitro release of insulin from nanoparticles were determined under phosphate buffer (pH = 6.8) condition. Although a quadratic model has been chosen to fit the responses for size, PdI, and EE%, the zeta potential of the particles has been best fitted to 2-FI model. The optimized nanoparticles were characterized. The size of the particles were found to be 346, 318, and 289 nm; zeta potentials were 28.5, 27.7, and 22.2 mV; PdI of particles were 0.305, 0.333, and 0.437; and calculated EE% were 70.3%, 84.5%, and 69.2%, for methylated (aminobenzyl), methylated (pyridinyl), and methylated (benzyl) chitosan nanoparticles, respectively. TEM images show separated and non-aggregated nanoparticles with sub-spherical shapes and smooth surfaces. An in vitro release study of the prepared nanoparticles showed that the cumulative percentage of insulin released from the nanoparticles were 47.1%, 38%, and 68.7% for (aminobenzyl), (pyridinyl), and (benzyl) chitosan, respectively, within 300 min.

Effect of whey protein- and xanthan-based coating on the viability of microencapsulated Lactobacillus acidophilus and physiochemical, textural, and sensorial properties of yogurt.

The goal of this study was to investigate the viability of microencapsulated and coated Lactobacillus acidophilus in yogurt during storage in a refrigerator for 28 days and in simulated gastrointestinal conditions. Furthermore, the effect of the microencapsulated and coated L. acidophilus on the physicochemical, textural, and sensory properties of yogurt was assessed. Lactobacillus acidophilus was microencapsulated in sodium alginate and coated with xanthan and/or whey protein. The coating led to the increase in the microcapsule diameter and the microencapsulation yield, while it led to the decreased moisture and water activity (aw) of the microcapsule. The survival of L. acidophilus microcapsule coated with whey protein and xanthan in yogurt during storage and exposure to simulated gastrointestinal conditions was significantly increased. Compared with free bacteria, the L. acidophilus microcapsule coated with whey protein and xanthan had the increased viability in yogurt until 2.16 log CFU/g during storage and 3.52 log CFU/g in simulated gastrointestinal conditions. After the 28th day of storage, a significant difference between the acidity and pH of yogurt containing coated and microencapsulated L. acidophilus and control yogurt was not observed. However, yogurt containing free L. acidophilus had lower pH and higher acidity and showed a significant difference (p < .05) with other samples. Although the coating of L. acidophilus microcapsule did not affect the sensory properties and gumminess of yogurt, it increased the firmness, adhesiveness, and viscosity of this product and caused a significant decrease in syneresis and cohesiveness. In general, the application of whey protein and xanthan coating on L. acidophilus microcapsule surface could increase the viability of this probiotic in yogurt during storage and in simulated gastrointestinal conditions and improve the texture attributes of yogurt.

Design and Optimization of Cationic Nanocapsules for Topical Delivery of Tretinoin: Application of the Box-Behnken Design, In Vitro Evaluation, and Ex Vivo Skin Deposition Study.

Cationic nanocapsules represent a promising approach for topical delivery purposes. We elaborated on a novel formulation based on the cationic nanocapsules to enhance the pharmacodynamic efficacy, user compliance, and photostability of tretinoin (TTN). To achieve this goal, TTN nanocapsules were prepared by the nanoprecipitation method. In order to statistically optimize formulation variables, a Box-Behnken design, using Design-Expert software, was employed. Three independent variables were evaluated: total weight of the cationic acrylic polymer (X 1), oil volume (X 2), and TTN amount (X 3). The particle size and encapsulation efficiency percent (EE%) were selected as dependent variables. The optimal formulation demonstrated spherical morphology under scanning electron microscopy (SEM), optimum particle size of 116.3 nm, and high EE% of 83.2%. TTN-loaded nanocapsules improved photostability compared to its methanolic solution. The in vitro release study data showed that tretinoin was released in a sustained manner compared to the free drug. The ex vivo skin permeation study demonstrated that greater drug deposition into the epidermal region rather than the deep skin was observed with a gel containing TTN-loaded nanocapsules than that of drug solution, respectively. The skin irritation test revealed that the nanoencapsulation of the drug decreased its irritancy compared to the free drug. These results revealed the promising potential of cationic nanocapsules for topical delivery of tretinoin.