Development of electrosprayed artesunate-loaded core–shell nanoparticles

Objective: Artesunate (ART) is proven to have potential anti-proliferative activities, but its instability and poor aqueous solubility limit its application as an anti-cancer drug. The present study was undertaken to develop coaxial electrospraying as a novel technique for fabricating nanoscale drug delivery systems of ART as the core–shell nanostructures.

Methods: The core–shell nanoparticles (NPs) were fabricated with coaxial electrospraying and the formation mechanisms of NPs were examined. The physical solid state and drug–polymer interactions of NPs were characterized by X-ray powder diffraction (XRPD) and Fourier transform infrared (FTIR) spectroscopy. The effects of materials and electrospraying process on the particle size and surface morphology of NPs were investigated by scanning electron microscopy (SEM). The drug release from NPs was determined in vitro by a dialysis method.

Results: The ART/poly(lactic-co-glycolic) acid (PLGA) chitosan (CS) NPs exhibited the mean particle size of 303?±?93?nm and relatively high entrapment efficiency (80.5%). The release pattern showed an initial rapid release within two hours followed by very slow extended release. The release pattern approached the Korsmeyer–Peppas model.

Conclusions: The present results suggest that the core–shell NPs containing PLGA and CS have a potential as carriers in the anticancer drug therapy of ART.     

Nanocrystal-based drug delivery system of risperidone: lyophilization and characterization

Objective: In the present work nanocrystal-based formulation of risperidone (RIS) was proposed to overcome solubility issue of RIS, while lyophilization technique was used effectively, for conversion of RIS nanosuspension to solid state.

Significance: RIS nanosuspension was developed and stabilized with a combination of polycaprolactone and Pluronic^® F-68 as stabilizers. With focus on critical parameters like nature of cryoprotectants and effect of eutectic temperature on properties of nanosuspension, the suitability of lyophilization technique in improving the physical stability of prepared nanosuspension was also evaluated. Additionally, the developed nanocrystals were also assessed for their solid states properties.

Methods: Various process parameters affecting average particle size and polydispersity index (PDI), viz. drug to surfactant ratio, solvent to anti-solvent ratio, stirring speed, type of stabilizer were optimized. Assessment of lyophilization as a suitable solidification technique (for conversion to powder form) was done with selective cryoprotectants (trehalose dihydrate and sorbitol).

Results: The formulation was found to be stable at 4?°C for 3 months with size, PDI and zeta potential of 214?±?3.4?nm, 0.120, and –10.2?±?0.90?mV, respectively. Release profile of developed nanosuspension showed cumulative % release of ～90% in initial 10?h whereas the value for the unprocessed drug was ～11% in same time frame.

Conclusions: These findings suggest that developed formulation was able to enhance water solubility of the drug effectively and can be potentially used in the management of psychotic disorders.     

Dual-purpose vardenafil hydrochloride/dapoxetine hydrochloride orodispersible tablets: in vitro formulation/evaluation,stability study and in vivo comparative pharmacokinetic study in healthy human subjects

Erectile dysfunction (ED) is the most important disorder after premature ejaculation for sexual activity in men. Vardenafil hydrochloride (VH) is an oral therapy for the treatment of erectile dysfunction. VH oral disintegrating tablets (ODTs) have been prepared by freeze drying technique to improve its dissolution profile and the overall clinical performance. Dapoxetine hydrochloride (DH) was added to the best three formulae of the prepared VH ODTs to treat premature ejaculation. All the ODTs formulae were evaluated for weight variation, friability, drug content, in vitro disintegration time, wetting time, and the dissolution study. Gelatin as a matrix former with N-methylpyrrolidone as a solubilizer in VH/DH ODTs improved the dissolution rate and extent of release of VH and DH with 100% of drug being dissolved after 15?min. In vivo study results from six healthy male volunteers showed shorter T_max of VH from VH/DH ODT of 0.583?±?0.129?h and shorter T_max of DH from VH/DH ODT of 0.625?±?0.137?h and showed AUC_0–12 of VH from VH/DH ODT of 39.234?±?10.932?ng/ml^?h¹ and AUC_0–12 of DH from VH/DH ODT of 531.681?±?129.544?ng/ml^?h¹, with relative bioavailability values of 100.9 and 85%, respectively, compared to (Levitra^®) and (Priligy^®).     

Preformulation characterization and in vivo absorption in beagle dogs of JFD,a novel anti-obesity drug for oral delivery

JFD (N-isoleucyl-4-methyl-1,1-cyclopropyl-1-(4-chlorine)phenyl-2-amylamine·HCl) is a novel investigational anti-obesity drug without obvious cardiotoxicity. The objective of this study was to characterize the key physicochemical properties of JFD, including solution-state characterization (ionization constant, partition coefficient, aqueous and pH-solubility profile), solid-state characterization (particle size, thermal analysis, crystallinity and hygroscopicity) and drug-excipient chemical compatibility. A supporting in vivo absorption study was also carried out in beagle dogs. JFD bulk powders are prismatic crystals with a low degree of crystallinity, particle sizes of which are within 2–10?μm. JFD is highly hygroscopic, easily deliquesces to an amorphous glass solid and changes subsequently to another crystal form under an elevated moisture/temperature condition. Similar physical instability was also observed in real-time CheqSol solubility assay. pK_a (7.49?±?0.01), log?P (5.10?±?0.02) and intrinsic solubility (S₀) (1.75?μg/ml) at 37?°C of JFD were obtained using potentiometric titration method. Based on these solution-state properties, JFD was estimated to be classified as BCS II, thus its dissolution rate may be an absorption-limiting step. Moreover, JFD was more chemically compatible with dibasic calcium phosphate, mannitol, hypromellose and colloidal silicon dioxide than with lactose and magnesium stearate. Further, JFD exhibited an acceptable pharmacokinetic profiling in beagle dogs and the pharmacokinetic parameters T_max, C_max, AUC_0–t and absolute bioavailability were 1.60?±?0.81?h, 0.78?±?0.47?μg/ml, 3.77?±?1.85?μg·h/ml and 52.30?±?19.39%, respectively. The preformulation characterization provides valuable information for further development of oral administration of JFD.     

Preparation,characterization, and pharmacokinetics study of a novel genistein-loaded mixed micelles system

Genistein (GEN), is a natural dietary isoflavone, has been reported to show anticancer activities. However, its poor aqueous solubility and oral bioavailability limit its clinical application. We designed a novel genistein-loaded mixed micelles (GEN-M) system composed of Soluplus^® and Vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared by organic solvent evaporation aimed to overcome the challenges of GEN’s poor solubility and then further improve its oral bioavailability. The optimized, spherical-shaped GEN-M was obtained at a ratio of 10:1 (Soluplus^®:TPGS). The mean particle size of GEN-M was 184.7?±?2.8?nm, with a narrow polydispersity index (PDI) of 0.162?±?0.002. The zeta potential value of GEN-M was ?2.92?±?0.01?mV. The micelles solutions was transparent with blue opalescence has high the entrapment efficiency (EE) and drug loading (DL) of 97.12?±?2.11 and 3.87?±?1.26%, respectively. GEN-M was demonstrated a sustained release behavior when formed micelles shown in drug release in vitro. The solubility of GEN in water increased to 1.53?±?0.04?mg/mL after encapsulation. The permeability of GEN across a Caco-2 cell monolayer was enhanced, and the pharmacokinetics study of GEN-M showed a 2.42-fold increase in relative oral bioavailability compared with free GEN. Based on these findings, we conclude that this novel nanomicelles drug delivery system could be leveraged to deliver GEN and other hydrophobic drugs.     

Preparation and evaluation of isoliquiritigenin-loaded F127/P123 polymeric micelles

Isoliquiritigenin (ISL) possesses a variety of pharmacological activities amid poor solubility in water which has restricted its clinical application. In this study, isoliquiritigenin-loaded F127/P123 polymeric micelles (ISL-FPM) were successfully prepared and evaluated in vitro and in vivo. The particle size, polydispersity index, and zeta potential of the selected formulation were 20.12?±?0.72?nm, 0.183?±?0.046, and ?38.31?±?0.33?mV, respectively, coupled with high encapsulation efficiency of 93.76?±?0.31%. Drug-loading test showed the solubility of ISL after formulating into micelles was 232 times higher than its intrinsic solubility. Moreover, critical micelle concentration (CMC) was tested with fluorescence probe method and turned out to be quite low, which implied high stability of ISL-FPM. Release profile in HCl (pH 1.2), double distilled water, and PBS (pH 7.4) of ISL-FPM reached over 80%, while free ISL was around 40%. Pharmacokinetic research revealed that formulated ISL-FPM significantly increased bioavailability by nearly 2.23-fold compared to free ISL. According to the results of in vitro antioxidant activity, scavenging DPPH activity of ISL was significantly strengthened when it was loaded into polymeric micelles. Altogether, ISL-FPM can act as a promising approach to improve solubility as well as enhance bioavailability and antioxidant activity of ISL.     

Delivery of vinblastine-containing niosomes results in potent in vitro/in vivo cytotoxicity on tumor cells

Vinblastine (VB), as a chemotherapeutic agent, is widely used in treatment of different types of cancer. However, its clinical application is limited due to its low water solubility, side effects, and multidrug resistance. The aim of this study was to increase the therapeutic efficacy of VB using drug delivery systems. For this purpose, a PEGylated niosomal formulation of vinblastine (Pn-VB) was prepared by thin film hydration method and physicochemically characterized. Drug release pattern was performed by dialysis diffusion method. The cytotoxicity of Pn-VB was investigated against murine lung cancer TC-1 cells using MTT assay and its tumor inhibitory effect was evaluated in lung tumor-bearing C57BL/6 mice. Mean particle size, zeta potential, entrapment, and loading efficiency of niosomes were obtained to be about 234.3?±?11.4?nm, -34.6?±?4.2?mV, 99.92?±?1.6%, and 2.673?±?0.30%, respectively. While, the mean particle size and zeta potential for non-PEGylated niosomes were obtained about 212.4?nm and -31.4?mV, respectively. The in vitro release pattern of drug from niosomes showed a sustained release behavior. Pn-VB indicated a significant increase in toxicity against TC-l cells as compared to free VB. In animal model, Pn-VB exhibited stronger tumor inhibitory effect and longer life time in comparison to free VB. In conclusion, Pn-VB showed appropriate stability, high-entrapment efficacy, lower releasing rate, and stronger cytotoxic activity against lung cancer TC-1 cells as compared to free drug. Thus, the Pn-VB could be a promising formulation for delivery of vinblastine to tumor cells with enhanced drug bioavailability and therapeutic efficacy.     

Comparative study of different approaches for preparation of chlorzoxazone orodispersible tablets

Abstract

Context: Muscle spasm is a painful involuntary contraction of muscles, which causes involuntary movement and distortion. Chlorzoxazone is a centrally acting muscle-relaxant with sedative properties, but given orally, it is hepatically metabolized leading to decreased bioavailability.

Objective: Orodispersible tablets (ODTs) of chlorzoxazone were formulated using two different approaches; by coprocessed excipients (CE) or by liquisolid (LS) technique.

Materials and methods: Pharmaburst^® 500, Starlac^®, Pearlitol flash^®, Prosolv^® odt and F-melt^® were used as coprocessed superdisintegrants, whereas in LS, Avicel^® PH101, Microcelac^® 100 and Cellactose^® 80 were used as carriers, while Aerosil^® 200 was the coating material. ODTs were evaluated in terms of weight and thickness variations, drug content, hardness, friability, wetting time, dissolution, disintegration time (DT) and palatability.

Results: In vitro DT of CE-ODTs ranged from 26.43?±?1.693?s to >180?s, whereas it was between 25.42±?0.203?s to >180?s in LS-ODTs. Complete drug release within 15?min was attained by CE1 prepared with 92.5?mg Pharmaburst^® 500. In vivo DT of CE1 and LS3 were 19.779?±?0.810 and 18.105?±?0.423?s, respectively, using six volunteers. Volunteers found that CE1 had more acceptable taste and was more palatable than LS3.

Conclusion: It was concluded that chlorzoxazone ODTs could be successfully formulated using either CE or LS techniques and be used as novel dosage forms for pediatrics and geriatrics showing improved drug release. Moreover, CE technique was superior to LS technique in terms of palatability.     

In vitro/in vivo evaluation of felodipine micropowders prepared by the wet-milling process combined with different solidification methods

In order to improve the in vitro dissolution rate and in vivo oral bioavailability of the poorly water soluble drug, felodipine (FELO), the wet-milling process was employed involving co-grinding with HPMC E5 and the in vitro release rate as investigated. After solidification by spray drying or freeze drying, the microsized powders were characterized in terms of their size, morphology, and in vitro dissolution rate. The oral bioavailability of this dry powder for suspension was evaluated in rats. After milling with 8% HPMC E5 and freeze drying, the powder mixture had an average particle size of 2.249?±?1.497?μm and displayed an excellent dissolution rate of up to 93.2% within 10?minutes. DSC and PXRD investigations confirmed the absence of any crystal transformation during the wet-milling process. Using two different solidification methods, powders were stable for 6 months with regard to their in vitro dissolution rate. Significantly improved bioavailability was obtained for the wet-milled suspension before solidification and freeze dried powders with 6.8- (p?p?p?>?0.05) in bioavailability was seen for the spray dried powders. These effects suggest that the solidification method plays an important role in modifying the bioavailability of FELO after wet milling. Consequently, wet-milling is an effective technique to enhance the bioavailability of FELO and to maintain these benefits, freeze-drying is a feasible approach to solidifying the wet-milled suspension for industrial applications.     

In vitro and in vivo evaluation of folate-mediated PEGylated nanostructured lipid carriers for the efficient delivery of furanodiene

Furanodiene (FN) loaded FA-PEG₂₀₀₀-DSPE modified nanostructured lipid carriers (FA-FN-NLCs) were developed to increase the solubility and bioavailability of FN, prolong the circulation time in blood and improve the targeting ability. FA-FN-NLCs were prepared using emulsification-ultrasonic and low temperature-solidification method and optimized by central composition design (CCD). In vitro and in vivo characteristics of FA-FN-NLCs were investigated in detail. The optimized formulations exhibited a spherical shape with particle size of 127.4?±?2.62?nm, PDI of 0.268?±?0.04, zeta potential of –14.7?±?1.08?mV, high encapsulation efficiency of 89.04?±?2.26% and loading capacity of 8.46?±?0.20%. Differential scanning calorimetry (DSC) indicated that FN was not in crystalline state in FA-FN-NLCs. In vitro drug release exhibited a biphasic release pattern which showed a relative burst drug release at the initial time and followed by a prolonged drug release. In vivo, compared with FN solution (FN-SOL) and FN loaded traditional NLCs (FN-NLCs), FA-FN-NLCs had a longer blood circulating time (t_1/2) and higher area under the curve (AUC). NiR fluorescence imaging study demonstrated that FA-FN-NLCs specially accumulated in tumor site by the receptor-mediated endocytosis. This study showed that FA-FN-NLCs was a promising drug delivery system for FN in the treatment of cancer.     

Formulation and pharmacokinetics of gelucire solid dispersions of flurbiprofen

Context: Development of solid dispersions is to improve the therapeutic efficacy by increasing the drug solubility, dissolution rate, bioavailability as well as to attain rapid onset of action.

Objective: The present research deals with the development of solid dispersions of flurbiprofen which is poorly water soluble to improve the solubility and dissolution rate using gelucires.

Materials and methods: In this study, solid dispersions were prepared following solvent evaporation method using gelucire 44/14 and gelucire 50/13 as carriers in different ratios. Then the formulations were evaluated for different physical parameters, solubility studies, DSC, FTIR studies and in vitro dissolution studies to select the best formulation that shows rapid dissolution rate and finally subjected to pharmacokinetic studies.

Results and discussion: From the in vitro dissolution study, formulation F3 showed the better improvement in solubility and dissolution rate. From the pharmacokinetic evaluation, the control tablets produced peak plasma concentration (C_max) of 9140.84?±?614.36?ng/ml at 3?h T_max and solid dispersion tablets showed C_max?=?11?445.46?±?149.23?ng/ml at 2?h T_max. The area under the curve for the control and solid dispersion tablets was 31?495.16?±?619.92 and 43?126.52?±?688.89?ng h/ml and the mean resident time was 3.99 and 3.68?h, respectively.

Conclusion: From the above results, it is concluded that the formulation of gelucire 44/14 solid dispersions is able to improve the solubility, dissolution rate as well as the absorption rate of flurbiprofen than pure form of drug.     

Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation,characterization, plasma,and kidney pharmacokinetics

The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6?±?5.95?nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71?±?3.02%, and the drug loading was 1.56?±?0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUC_kidney/AUC_plasma?=?0.586?±?0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.     

Development of a nanoemulsion of Phyllanthus emblica L. branch extract

For potential topical administration, we formulated a nanoemulsion containing phenolic constituents of Phyllanthus emblica branch extract. The nanoemulsion has high entrapment efficiency, small particle size, is stable, and can release its main chemical components. Branches of P. emblica were extracted with 50% ethanol (EPE) with 5.4% yield. HPLC analysis indicated several phenolic compounds, including gallic acid, vanillic acid, epigallocatechin (EGC), epigallocatechin gallate (EGCG) and ellagic acid. These were selected as chemical markers of EPE in the nanoemulsion development. The nanoemulsion was prepared by microemulsion techniques with hot high pressure homogenization. A ternary phase diagram was constructed to obtain the optimized nanoemulsion. The obtained transparent EPE nanoemulsion is composed of isopropyl myristate (0.6% w/w), Brij® 78 (0.35% w/w), and 0.15% (w/w) EPE. The optimized EPE nanoemulsion had a median particle size of 191.63?±?4.07?nm with a narrow particle size distribution, a zeta potential of ?10.19?±?0.54?mV, high entrapment efficiency at 67.99?±?0.87% and good stability at 4?°C after 90?d of storage. The release of active ingredients from the EPE nanoemulsion was slower than that of the EPE aqueous formulation. The loading ratios of the five phenolic compounds were high, with relative order of EGC?>?EGCG?>?vanillic acid?>?gallic acid?>?ellagic acid, resulting in slow release profiles of EGC and EGCG in the EPE nanoemulsion. In conclusion, the obtained EPE nanoemulsion has good characteristics for future clinical trials.     

Capecitabine lipid nanoparticles for anti-colon cancer activity in 1,2-dimethylhydrazine-induced colon cancer: preparation,cytotoxic, pharmacokinetic,and pathological evaluation

The cornerstone of this investigation is to determine the pharmacokinetic and histopathological behavior of solid lipid nanoparticles of capecitabine (CB-SLNs) in 1,2-dimethylhydrazine (DMH) induced colon cancer. The nanoparticles were prepared by microemulsion method. CB-SLNs were characterized for an optimal system. The cytotoxicity of CB-SLNs was evaluated by using MTT assay method. Further, pharmacokinetic and histopathological behavior of SLNs were studied in DMH induced colon cancer rats. The optimized nanoparticles have the particle size, zeta potential, and entrapment efficiency of 145.6?±?3.6?nm, ?26.9?±?2.7?mV, and 88.33?±?3.74%, respectively. Particles of CB were nearly spherical in shape and converted to amorphous form revealed by SEM and DSC, XRD studies. The nanoparticles showed dose-dependent cytotoxicity activity from 10 to 125?µg/mL compared with suspension. Pharmacokinetic studies revealed that 2.7-folds enhancement in the oral bioavailability and in aberrant crypt foci number, apoptotic index comparison with suspension formulation.     

Hyperoside nanocrystals for HBV treatment: process optimization,in vitro and in vivo evaluation

The aim of this study was to develop hyperoside (Hyp) nanocrystals to enhance its dissolution rate, oral bioavailability and anti-HBV activity. Hyp nanocrystals were prepared using high pressure homogenization technique followed by lyophilization. A Box–Behnken design approach was employed for process optimization. The physicochemical properties, pharmacokinetics and anti-HBV activity in vivo of Hyp nanocrystal prepared with the optimized formulation were systematically investigated. Hyp nanocrystals prepared with the optimized formulation was found to be rod shaped with particle size of 384?±?21?nm and PDI of 0.172?±?0.027. XRPD studies suggested slight crystalline change in drug. Dissolution rate obtained from Hyp nanocrystals were markedly higher than pure Hyp. The nanocrystals exhibited enhanced C_max (7.42?±?0.73 versus 3.80?±?0.66?mg/L) and AUC_0???t (193.61?±?16.30 versus 91.92?±?17.95?mg·h/L) with a 210.63% increase in relative bioavailability. Hyp nanocrystals exhibited significantly greater anti-HBV activity than Hyp. These results suggested that the developed nanocrystals formulation had a great potential as a viable approach to enhance the bioavailability of Hyp.     

Preparation and characterization of solid lipid nanoparticles of furosemide using quality by design

The present work aimed to synthesize solid lipid nanoparticles (SLNs) of Furosemide (FRSM). The parameter sensitivity analysis showed a significant effect of particle size and reference solubility on the AUC_0–∞, C_max and t_max. The FRSM-encapsulated SLNs were synthesized by the phase inversion temperature (PIT) technique using 3² factorial design. The optimal level of 221.28?mg of Compritol 888 ATO and 420?mg of Cremophor RH 40 showed a mean hydrodynamic diameter (MHD) of 25.54?±?0.57?nm, a polydispersity index (PdI) of 0.158?±?0.01, the % entrapment efficiency of 80.70?±?4.06%, percent dissolution efficiency of 71.72?±?1.52% and time elapsed for 50% drug release of 3.67?±?0.15?h. The PIT was determined using the turbidity method and the values ranged between 75°C and 73°C. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) images represent spherical to sub-spherical and smooth surface of SLN. The Fourier transform-infrared (FTIR), differential scanning calorimetry (DSC) and x-ray diffraction (XRD) depict the drug-excipient compatibility. Korsmeyer–Peppas was found to be the best fit release kinetics model (R²?=?0.973; K-value?=?29.96 and release exponent?=?0.40), predicting the Fickian diffusion. The results advocate that the optimized formulation (OF) could promote the controlled release, and improve the physicochemical stability of the formulation. Hence, SLN could be a potential drug carrier for the peroral delivery of FRSM.     

Study of physicochemical properties of flutamide-loaded Ocimum basilicum microspheres with ex vivo mucoadhesion and in vitro drug release

Drug which shows extensive first pass effect is difficult task that, needs to be solved by formulators in the pharmaceutical science. The low oral bioavailability (49%) of flutamide may be due to poor wettability, low aqueous solubility and extensive first pass effect. The aim of present investigation was to prepare flutamide loaded microspheres and incorporate it into suppositories for rectal delivery to avoid first pass effect and enhance residence time. Flutamide loaded mucoadhesive microspheres of Ocimum Basilicum mucilage (OBM) were prepared using spray drying and characterized by percent production yield, encapsulation efficiency, particle size, zeta potential, polydispersity index, DSC, SEM, XRPD, in vitro drug release and stability studies. Moreover, ex vivo mucoadhesion was investigated using falling liquid film technique to determine the adhesion of microspheres to sheep rectal mucosa. The microspheres had nearly spherical shape and size about 2.53?μm. The encapsulation efficiency and mucoadhesion of optimized formulation MBF10 were found to be 69.6?±?2.3% and 89.01?±?2.18%, respectively. Percent CDR of optimized flutamide loaded mucoadhesive microspheres was found to be 88.7?±?1.3 at 7?h. In conclusion, OBM microparticles based suppository could be used to deliver drug through rectal delivery.     

Acalypha indica–mediated green synthesis of ZnO nanostructures under differential thermal treatment: Effect on textile coating,hydrophobicity, UV resistance,and antibacterial activity

In this study, ZnO nanoparticles were green-synthesized from Acalypha indica leaf extract using zinc acetate as a precursor. The prepared ZnO nanoparticles were calcined at three different temperatures, namely 100, 300, and 600?°C. The structure/morphology of the green-synthesized ZnO nanoparticles was ascertained through X-ray diffraction, particle size analysis, scanning electron microscopy, transmission electron microscopy, and surface area analysis techniques. It was observed from the physico-chemical and biological characterization studies that ZnO nanoparticles calcined at high temperature (600?°C) exhibit high surface area (230?m²?g^?1) and small particle size (20?nm) with good antibacterial activity against Escherichia coli (22.89?±?0.06?mm) and Staphylococcus aureus (24.62?±?0.08?mm). In addition, cotton fabrics coated with these nanoparticles showed higher UV-protection (87.8?UPF), hydrophobicity (155°), and maximum zone of bacterial inhibition against E. coli and S. aureus (25.13?±?0.05 mm and 30.17?±?0.03?mm) than those coated with particles calcined at 100?°C and 300?°C. High temperature calcination has a vital role in the crystallization of the particles towards nanoscale with increased resistivity to UV exposure, washing treatments, and microbial infection in fabrics. Thus, the cost-effective ZnO nanoparticles obtained through green synthesis method proves their potential applications in the field of biomedical, textile, and cosmetic applications.     

Preparation and evaluation of Baicalin-loaded cationic solid lipid nanoparticles conjugated with OX26 for improved delivery across the BBB

Purpose: A novel brain targeting drug delivery system based on OX26 antibody conjugation on PEGylated cationic solid lipid nanoparticles (OX26-PEG-CSLN) was prepared.

Methods: The Baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody (OX26-PEG-CSLN) were prepared by emulsion evaporation–solidification at low temperature method. The immune-gold labeled OX26-PEG-CSLN was visualized by transmission electron microscopy. The mean diameter and zeta potential of OX26-PEG-CSLN, PEG-CSLN and CSLN were determined using a Zetasizer. The entrapment efficiency of OX26-PEG-CSLN, PEG-CSLN and CSLN was determined by ultrafiltration centrifugation method. And the solid-state characterization of OX26-PEG-CSLN and CSLN were analyzed by X-ray. Pharmacokinetics studies were conducted by in vivo microdialysis in rat cerebrospinal fluid.

Results: The results showed that the OX26-PEG-CSLN, PEG-CSLN and CSLN had average diameters of 47.68?±?1.65, 27.20?±?1.70 and 33.89?±?5.74?nm, Zeta potentials of ?0.533?±?0.115?mV, 11.200?±?0.500?mV and 11.080?±?1.170?mV and entrapment efficiencies of 83.03?±?0.01%, 92.90?±?3.50% and 97.83?±?0.19%, respectively. In the pharmacokinetics studies, the AUC value of OX26-PEG-CSLN was11.08-fold higher than that of the Baicalin solution (SOL) (p?p?>?0.05); the C_max value of OX26-PEG-CSLN was 7.88-fold higher than that of SOL (p?p?Conclusion: These results demonstrated OX26-PEG-CSLN could be a promising carrier to deliver drugs across the BBB for the treatment of brain diseases.     

Bortezomib-loaded solid lipid nanoparticles: preparation,characterization, and intestinal permeability investigation

Bortezomib (BTZ), a proteasome inhibitor, is clinically used for the treatment of multiple myeloma and mantle cell lymphoma via intravenous or subcutaneous administration. Since BTZ has limited intestinal permeability, in this study, solid lipid nanoparticles (SLNs) were selected as lipid carrier to improve the intestinal permeability of BTZ. The nanoparticles were prepared by hot oil-in-water emulsification method and characterized for physicochemical properties. Moreover, in situ single-pass intestinal perfusion technique was used for intestinal permeability studies. Mean particle size of the BTZ-loaded solid lipid nanoparticles (BTZ-SLNs) was 94.6?±?0.66?nm with a negative surface charge of –18?±?11?mV. The entrapment efficiency of the BTZ-SLNs was 68.3?±?3.7% with a drug loading value of 0.8?±?0.05%. Cumulative drug release (%) over 48?h, indicated a slow release pattern for nanoparticles. Moreover, the SEM image showed a spherical shape and uniform size distribution for nanoparticles. Also, FTIR analysis indicated that BTZ was successfully loaded in the SLNs. The results of the intestinal perfusion studies revealed an improved effective permeability for BTZ-SLNs with a P_eff value of about threefold higher than plain BTZ solution.