Nanosize Range Research Articles

Hydrogen storage properties of 2Mg-Fe mixtures processed by hot extrusion at different temperatures

2Mg-Fe mixtures produced by high-energy ball milling were consolidated into bulk form by hot extrusion at different processing temperatures (573 K (300 °C), 623 K (350 °C) and 673 K (400 °C)), aiming to evaluate their influence on the structure and microstructure of bulk materials and their consequent influence on the hydrogen sorption properties. In spite being in the nanosize range, the highest the processing temperature, the larger the grain sizes. However, the nanometric grain size remained after any hot extrusion condition, as estimated by Rietveld refinement. The pinning effect of Fe on Mg grain boundaries explained this effect. In the first absorption (activation), powders showed a hydrogen storage capacity of ∼4.53 wt%, while the extruded samples (bulk materials) reached almost the same capacity during the period of hydrogenation (∼94% of the maximum hydrogen storage capacity for Mg2FeH6 - 5.5 wt%). The smallest crystallite sizes and highest surface area for hydrogenation explain the good performance of powders. However, when comparing only extruded samples, it was observed that the highest capacity and the lowest incubation times were mainly related to grain sizes and to the favorable texture along (002) plane of αMg. The desorption temperature of bulk materials was very similar to that of powders, which is good considering the lower surface area of bulk materials.

PH-Sensitive Polymeric Nanoparticles Fabricated by Dispersion Polymerization for the Delivery of Bioactive Agents.

Development of pH-responsive nanoparticles capable of rapid degradation in the acidic environments in the endosomes and lysosomes of tumor tissues but relatively more stable in the physiological pH (pH 7.4) is desirable. To show that the number of methoxy groups on the benzene ring of benzaldehyde bisacrylate acetal crosslinkers should affect the rate of hydrolysis of the crosslinkers and in vitro availability of the drug loaded into the nanoparticles. Three pH-sensitive acetal crosslinkers were synthesized and characterized by 1H NMR, 13C NMR, FT-IR and high resolution mass spectroscopy (HR-MS). The nanoparticles were fabricated by free-radical dispersion polymerization method. Hydrolysis studies were carried out on the crosslinkers and nanoparticles; drug release studies were done on docetaxel-loaded nanoparticles at pH 5.0 and pH 7.4. The statisitical experimental design was randomized complete block design followed by analyses of variance with F-test of significance. Pairwise comparison test was used to locate specific differences among parameters of the crosslinkers and the nanopaticles. Scanning electron micrographs showed the formation of spherical particles. Particle size analysis showed that the nanoparticles are within nanosize range with negative zeta potential. Data showed that the rate of hydrolysis and drug release were faster at pH 5.0 compared to pH 7.4. Hydrolysis and drug release studies were dependent on the structure of the acetals: Di(2-methacryloyloxyethoxy)- [2,4,6-trimethoxyphenyl] methane crosslinker showed the fastest rate of hydrolysis, followed by di(2- methacryloyloxyethoxy)-[2,4-dimethoxyphe-nyl] methane and di(2-methacryloyloxyethoxy)-[4-methoxyphenyl] methane. The pH-responsive nanoparticles are suitable for the delivery of bioactive agents, especially anticancer drugs.

Acute respiratory effects and biomarkers of inflammation due to welding-derived nanoparticle aggregates

PurposeWelders are exposed to airborne particles from the welding environment and often develop symptoms work-related from the airways. A large fraction of the particles from welding are in the nano-size range. In this study we investigate if the welders’ airways are affected by exposure to particles derived from gas metal arc welding in mild steel in levels corresponding to a normal welding day.MethodIn an exposure chamber, 11 welders with and 10 welders without work-related symptoms from the lower airways and 11 non-welders without symptoms, were exposed to welding fumes (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Symptoms from eyes and upper and lower airways and lung function were registered. Blood and nasal lavage (NL) were sampled before, immediately after and the morning after exposure for analysis of markers of oxidative stress. Exhaled breath condensate (EBC) for analysis of leukotriene B4 (LT-B4) was sampled before, during and immediately after exposure.ResultsNo adverse effects of welding exposure were found regarding symptoms and lung function. However, EBC LT-B4 decreased significantly in all participants after welding exposure compared to filtered air. NL IL-6 increased immediately after exposure in the two non-symptomatic groups and blood neutrophils tended to increase in the symptomatic welder group. The morning after, neutrophils and serum IL-8 had decreased in all three groups after welding exposure. Remarkably, the symptomatic welder group had a tenfold higher level of EBC LT-B4 compared to the two groups without symptoms.ConclusionDespite no clinical adverse effects at welding, changes in inflammatory markers may indicate subclinical effects even at exposure below the present Swedish threshold limit (8 h TWA respirable dust).

Solidified self nano-emulsifying drug delivery system of rosuvastatin calcium to treat diet-induced hyperlipidemia in rat: in vitro and in vivo evaluations.

The present work focuses on preparing a solidified self nano-emulsifying drug-delivery system (S-SNEDDS) to improve the in vitro dissolution of rosuvastatin and to evaluate its antihyperlipidemic activity. Powder flow characterization demonstrated good flow properties. The drug-excipient compatibility study indicates no possible interaction. Transmission electron microscopy and scanning electron microscopy revealed nonaggregated, spherical nanosized globules. The globule-size analysis revealed droplet size in nanorange (∼100 nm). S-SNEDDS exhibited improved drug release (∼95%) as compared with rosuvastatin powder (51.89%) at 60 min. Upon antihyperlipidemic study, S-SNEDDS after 14th day of treatment revealed significant reduction in cholesterol (33.47%), triglycerides (40.77%) and atherogenic index (81.28%), while high-density lipoprotein (118.43%) was increased. The study indicates the great potential of S-SNEDDS for improving oral absorption of such poorly soluble drugs and their pharmacodynamic efficacy.

Using single nanoparticle tracking obtained by nanophotonic force microscopy to simultaneously characterize nanoparticle size distribution and nanoparticle-surface interactions.

Comprehensive characterization of nanomaterials for medical applications is a challenging and complex task due to the multitude of parameters which need to be taken into consideration in a broad range of conditions. Routine methods such as dynamic light scattering or nanoparticle tracking analysis provide some insight into the physicochemical properties of particle dispersions. For nanomedicine applications the information they supply can be of limited use. For this reason, there is a need for new methodologies and instruments that can provide additional data on nanoparticle properties such as their interactions with surfaces. Nanophotonic force microscopy has been shown as a viable method for measuring the force between surfaces and individual particles in the nano-size range. Here we outline a further application of this technique to measure the size of single particles and based on these measurement build the distribution of a sample. We demonstrate its efficacy by comparing the size distribution obtained with nanophotonic force microscopy to established instruments, such as dynamic light scattering and differential centrifugal sedimentation. Our results were in good agreement to those observed with all other instruments. Furthermore, we demonstrate that the methodology developed in this work can be used to study complex particle mixtures and the surface alteration of materials. For all cases studied, we were able to obtain both the size and the interaction potential of the particles with a surface in a single measurement.

Nanoparticles grown from methanesulfonic acid and methylamine: microscopic structures and formation mechanism.

Mechanisms of particle formation and growth in the atmosphere are of great interest due to their impacts on climate, health and visibility. However, the microscopic structures and related properties of the smallest nanoparticles are not known. In this paper we pursue computationally a microscopic description for the formation and growth of methanesulfonic acid (MSA) and methylamine (MA) particles under dry conditions. Energetic and dynamics simulations were used to assess the stabilities of proposed model structures for these particles. Density functional theory (DFT) and semi-empirical (PM3) calculations suggest that (MSA-MA)4 is a major intermediate in the growth process, with the dissociation energies, enthalpies and free energies indicating considerable stability for this cluster. Dynamics simulations show that this species is stable for at least 100 ps at temperatures up to 500 K, well above atmospheric temperatures. In order to reach experimentally detectable sizes (>1.4 nm), continuing growth is suggested to occur via clustering of (MSA-MA)4. The dimer (MSA-MA)4(MSA-MA)4 may be one of the smaller experimentally measured particles. Step by step addition of MSA to (MSA-MA)4, is also a likely potential growth mechanism when MSA is excess. In addition, an MSA-MA crystal is predicted to exist. These studies demonstrate that computations of particle structure and dynamics in the nano-size range can be useful for molecular level understanding of processes that grow clusters into detectable particles.

TiO2 (Nano)Particles Extracted from Sugar-Coated Confectionery

As the debate about TiO2 food additive safety is still open, the present study focuses on the extraction and characterisation of TiO2 (nano)particles added as a whitening agent to confectionary products, that is, chewing gum pellets. The aim was to (1) determine the colloidal properties of suspensions mutually containing TiO2 and all other chewing gum ingredients in biologically relevant media (preingestion conditions); (2) characterise the TiO2 (nano)particles extracted from the chewing gum coating (after ingestion); and (3) verify their potential photocatalysis. The particle size distribution, in agreement with the zeta potential results, indicated that a small but significant portion of the particle population retained mean dimensions close to the nanosize range, even in conditions of moderate stability, and in presence of all other ingredients. The dispersibility was enhanced by proteins (i.e., albumin), which acted as surfactants and reduced particle size. The particle extraction methods involved conventional techniques and no harmful chemicals. The presence of TiO2 particles embedded in the sugar-based coating was confirmed, including 17–30% fraction in the nanorange (<100 nm). The decomposition of organics under UV irradiation proved the photocatalytic activity of the extracted (nano)particles. Surprisingly, photocatalysis occurred even in presence of an amorphous SiO2 layer surrounding the TiO2 particles.

Preparation, Physicochemical Characterization and Anti-fungal Evaluation of Nystatin-Loaded PLGA-Glucosamine Nanoparticles.

Nystatin loaded PLGA and PLGA-Glucosamine nanoparticles were formulated. PLGA were functionalized with Glucosamine (PLGA-GlcN) to enhance the adhesion of nanoparticles to Candida Albicans (C.albicans) cell walls. Quasi-emulsion solvent diffusion method was employed using PLGA and PLGA-GlcN with various drug-polymer ratios for the preparation of nanoparticles. The nanoparticles were evaluated for size, zeta potential, polydispersity index, drug crystallinity, loading efficiency and release properties. DSC, SEM, XRPD, 1H-NMR, and FT-IR were performed to analyze the physicochemical properties of the nanoparticles. Antifungal activity of the nanoparticles was evaluated by determination of MICs against C.albicans. The spectra of 1H-NMR and FT-IR analysis ensured GlcN functionalization on PLGA nanoparticles. SEM characterization confirmed that particles were in the nanosize range and the particle size for PLGA and PLGA-GlcN nanoparticles were in the range of 108.63 ± 4.5 to 168.8 ± 5.65nm and 208.76 ± 16.85nm, respectively. DSC and XRPD analysis ensured reduction of the drug crystallinity in the nanoparticles. PLGA-GlcN nanoparticles exhibit higher antifungal activity than PLGA nanoparticles. PLGA-GlcN nanoparticles showed more antifungal activity with appropriate physicochemical properties than pure Nystatin and PLGA nanoparticles.

Improved synthesis of aluminium nanoparticles using ultrasound assisted approach and subsequent dispersion studies in di-octyl adipate

The present work reports on an efficient and simple one pot synthetic approach for aluminium nanoflakes and nanoparticles based on the intensification using ultrasound and provides a comparison with the conventional approach to establish the cutting edge process benefits. In situ passivation of aluminium particles with oleic acid was used as the method of synthesis in both the conventional and ultrasound assisted approaches. The aluminium nanoflakes prepared using the ultrasound assisted approach were subsequently dispersed in di-octyl adipate (DOA) and it was demonstrated that a stable dispersion of aluminium nanoflakes into di-octyl adipate (DOA) is achieved. The morphology of the synthesized material was established using the transmission electron microscopy (TEM) analysis and energy dispersive X-ray analysis (EDX) and the obtained results confirmed the metal state and nano size range of the obtained aluminium nanoflakes and particles. The stability of the aluminium nanoflakes obtained using ultrasound assisted approach and nanoparticles using conventional approach were characterized using the zeta potential analysis and the obtained values were in the range of −50 to +50mV and −100 to +30mV respectively. The obtained samples from both the approaches were also characterized using X-ray diffraction (XRD) and particle size analysis (PSA) to establish the crystallite size and particle distribution. It was observed that the particle size of the aluminium nanoflakes obtained using ultrasound assisted approach was in the range of 7–11nm whereas the size of aluminium nanoparticles obtained using conventional approach was much higher in the range of 1000–3000nm. Overall it was demonstrated that the aluminium nanoflakes obtained using the ultrasound assisted approach showed excellent morphological characteristics and dispersion stability in DOA showing promise for the high energy applications.

Synthesis and properties of precipitated cobalt ferrite nanoparticles

The formation and properties of cobalt ferrite were investigated with XRD, FT-IR, FE-SEM, Mössbauer and magnetometry. Cobalt ferrite samples were prepared (a) by combining coprecipitation Co(OH)2/2Fe(OH)3, using NaOH between pH 5.2 and 11.4 and autoclaving, and (b) by autoclaving the Co(OH)2/2Fe(OH)3 coprecipitate in a very strong alkaline medium. XRD and FE SEM showed that both CoFe2O4 crystallites and particles were in the nanosize range. The FT-IR spectra were typical of spinel ferrites. Cobalt ferrite precipitated at pH 7.2 and at 11.4 contained a small fraction of α-Fe2O3, whereas in the sample precipitated at pH 11.4 a very small amount (traces) of α-FeOOH were detected by FT-IR, additionally. Parameters obtained by Mössbauer spectroscopy suggested a structural migration of cobalt and iron ions in prepared cobalt ferrite spinels with the prolonged time of autoclaving. Magnetic measurements showed the magnetic behaviour typical of spinel ferrite nanoparticles.

Study of the mechanical and the thermal insulation properties of polyurethane coating containing chicken eggshell and rice husk ash as fillers

Purpose The main aim of this study was to examine the effects of chicken eggshell (CES) and rice husk ash (RHA) as fillers on the mechanical and the thermal insulation properties of polyurethane coatings. Design/methodology/approach CES and RHA were ground via ball milling set at different parameters, and the smallest particles size obtained were selected and used as fillers. Fillers of different weight proportions were mixed with other components such as binder, solvent and pigment to form various coating formulations and test samples were made via dip coating. A series of characterisations were conducted to analyse the thermal and mechanical properties of the coating. Findings The smallest particle size of CES and RHA was obtained after both of them had undergone grinding process at 400 rpm within 180 min. Morphological studies revealed that CES and RHA have irregular shape and high porosity. In crystallographic analysis, CES mainly composed of pure calcite crystal structure and RHA contained amorphous silica. Both of fillers were found thermally stable up to 520 and 710°C for RHA and CES, respectively. In RHA individual system, as the RHA proportion increases, the thermal conductivity of the coating declined. In contrast, in the CES coating system, the thermal conductivity demonstrated an opposite trend. Thermal gravimetric analysis results displayed that by adding hybrid fillers, the residue weight and the thermal stability of the coatings were increased. In addition, the adhesion strength of the coating was increased as the filler weight content increased. Research limitations/implications Fillers with nano-range size were expected to be produced in this research for better performance of the coating. However, the obtained fillers were limited to micron size through dry grinding method. Another drawback in this research was the coating technique which is dip coating. The coated substrates do not have uniform coating thickness and this subsequently influenced the performance. Originality/value A novel attempt has been made to study the formulation coating system by mixing CES and RHA as fillers which is also known as a hybrid system.

Increase of Fatigue Life of Titanium VT1-0 after Electron Beam Treatment

The processing of commercially pure titanium VT1-0 with high intensity pulsed electron beam was carried out and the mode of irradiation allowing the increase in fatigue life of the material was revealed. Structure investigations of modified layer and fracture surface of commercially pure titanium samples subjected to fatigue multicycle tests were implemented. By methods of scanning electron microscopy the structural transformations responsible for increase in fatigue life of titanium irradiated with high intensity pulsed electron beam were revealed. It was shown that irradiation of commercially pure titanium of grade VT1-0 with high intensity electron beam (25 J/cm2, 150 μs, 3 pulses) resulted in the refinement of grain structure, formation of multilayer structure. Irradiation facilitated the formation of additional structural levels of micro and nanosize range in surface layer.

Self-emulsifying phospholipid pre-concentrates (SEPPs) for improved oral delivery of the anti-cancer genistein: Development, appraisal and ex-vivo intestinal permeation

Genistein (GEN), a potent anticancer agent, suffers from scanty oral bioavailability due to poor solubility and extensive metabolism. This work endeavored to enhance GEN solubility and intestinal permeability via fabrication of self-emulsifying phospholipid pre-concentrates (SEPPs) using some bioactive surfactants. Moreover, the potential of surfactant-free SEPP to address GEN obstacles was investigated. SEPPs were prepared from Phosal® 53MCT, oil/phosphatidylcholine mixture, alone or with only 30% of different surfactant/co-surfactant mixture (S/CO). In-vitro characterization encompassed globule size analysis, zeta potential (ZP), transmission electron microscopy, and in-vitro release. Ex-vivo intestinal permeation study was performed using non-everted rat intestinal sac technique. Upon aqueous dilution, SEPPs were easily dispersed with spherical globules within a nano-range size (from 165±15 to 425±20nm) and adequate negative ZP (>−30mV). SEPPs demonstrated a significant enhancement in GEN release compared to drug suspension without superior effect due to added S/CO. Permeation study revealed that at least 12.13% free GEN was permeated after 120min from SEPPs compared to only 3.7% from drug suspension. Among different SEPPs, SEPP containing 30% Tween 80/Transcutol HP mixture showed the highest GEN permeation (18.54%). Conclusively, SEPP might be a promising nanocarrier that enhances GEN bioavailability via improving dissolution and inhibition of pre-systemic clearance.

Biodegradation of nanocrystalline cellulose by two environmentally-relevant consortia.

Nanocellulose is growing in popularity due to its versatile properties and applications. However, there is a void of knowledge regarding the environmental fate of nanocellulose and the response of environmental microbial communities that are historically adapted to non-nano cellulose forms. Given its distinction in terms of size and chemical and physical properties, nanocellulose could potentially resist biodegradation and/or pose a xenobiotic influence on microbial communities during wastewater treatment or in receiving environments. In this study, biodegradation of H2SO4 hydrolyzed nanocrystalline cellulose (HNC) was compared with that of microcrystalline cellulose using two distinct anaerobic cellulose-degrading microbial consortia initially sourced from anaerobic digester (AD) and wetland (W) inocula. Equivalent cellulose masses were dosed and monitored with time by measurement of liberated glucose. HNC biodegraded at slightly faster rate than microcrystalline cellulose (1st order decay constants: 0.62 ± 0.08 wk−1 for HNC versus 0.39 ± 0.05 wk−1 for microcrystalline cellulose for the AD consortium; 0.69 ± 0.04 wk−1for HNCversus 0.58 ± 0.05 wk−1 for microcrystalline cellulose for the W consortium). 16S rRNA (total bacteria) and cel48 (glycoside hydrolase gene family 48, indicative of cellulose-degrading potential) genes were observed to be more enriched in the HNC condition for both consortia. According to Illumina amplicon sequencing of 16S rRNA genes, the composition of the consortia underwent distinct shifts in concert with HNC versus microcrystalline cellulose degradation. This study demonstrates that the biodegradation of cellulose is not inhibited in the nano-size range, particularly in the crystalline form, though the microbes and pathways involved likely differ.

Effects of Zn-Cr-substitution on the structural and magnetic properties of Ni1−xZnxFe2−xCrxO4 ferrites

Cr and Zn-substituted nickel ferrites, general formula Ni1−xZnxFe2−xCrxO4 (x=0, 0.1, 0.3, 0.5, 0.7), were prepared using the sol-gel auto-combustion method. For precise analysis, the Ni1−xZnxFe2O4and NiFe2−xCrxO4 (x=0, 0.1, 0.3, 0.5, 0.7) samples were also checked individually. The effects of Cr and Zn doping on the structural, morphological, and magnetic properties of the samples were evaluated by X-ray diffraction (XRD), scanning electron microscopy (SEM), and vibrating sample magnetometer (VSM). The full pattern fitting of Rietveld method using MAUD program was also applied to determine the exact coordinates of the atoms, unit cell dimensions, and ion occupancy. XRD measurement by Rietveld refinement confirmed the crystalline structure and phase purity of all the ferrites. SEM images showed that the particles were in the nanosize range. VSM results revealed that the values of MS in the NiFe2−xCrxO4 samples decreased and that HC had no regular behavior with increasing Cr content. The maximum value of HC=16Oe was obtained for a Cr content of x=0.7. On the other hand, saturation magnetization values initially increased in both the Ni1−xZnxFe2−xCrxO4 and Ni1−xZnxFe2O4 samples, with changing the doping level up to x=0.3, while for further content, MS decreased. In addition, coercivity decreased with increasing doping level.

Effects of Ultrasound Irradiation on Synthesis of Solid Acid Catalysts

The studies based on morphological characterization to assess the effects of ultrasound irradiation on synthesis of solid acid catalysts. Three sets of catalyst formulation were synthesized by both wet impregnation method and ultrasound assisted methods with different wt. % of Ni loading on γ-Al2O3. The XRD, BET, TEM and FESEM techniques were used to characterize the nano-particles. Physicochemical characterization revealed that the synthesized catalysts particles using ultrasound irradiation were in nano size range (1-24.5 nm) with equal dispersion of metal oxide, high surface area with increase of metal loading and high phase purity than the catalysts synthesized conventional method. These catalysts were also found in various crystal structures like cubic, monoclinic and tetrahedral. The use of ultrasound irradiation has great significance over the wet impregnation method in relation to the rate of synthesis of nanocatalysts. The high surface area, high thermal stability and small particle size (up to 1 nm) are the basic elements for high activity of solid acid catalysts in hydrocracking and hydrodeoxygenation of various feedstock in petroleum industries.

The investigation of antistatic effects of 1-ethyl-2,3-dimethylimidazolium ethyl sulphate for acrylic-based polymer film

This study aims to produce a long-term antistatic acrylic-based film by incorporating ionic liquid (IL), 1-ethyl-2,3-dimethylimidazolium ethyl sulphate (EIL) into acrylic resin. After loading, characterisations of samples were conducted by mechanically, thermally and morphologically. In order to determine antistatic properties, surface resistivity of samples was measured by using at different time intervals. The results indicated that IL loaded polymers showed a good antistatic property for a long time. The effect of incorporation on tensile strength, tensile modulus, flexural strength and flexural modulus of polymer were also obtained. After loading process, tensile strength, tensile modulus, flexural strength and flexural modulus values decreased considerably. The decrement in tensile strength of polymer is much less than that in flexural strength. The effect of EIL incorporation into acrylic resin on thermal conductivity and surface wettability was also investigated. From scanning electron microscopy images, EIL particles in nano-size range were observed in polymer structure.

Design and in vitro characterization of ivermectin nanocrystals liquid formulation based on a top–down approach

The aim of this study was to develop ivermectin (IVM) nanosuspensions (NSs) to improve the dissolution rate of this poorly water-soluble drug. Different NSs combining different stabilizers, i.e. poloxamer 188 (P188), polysorbate 80 (T80), polyvinylpyrrolidone (PVP), and sodium lauryl sulfate (SLS), were prepared by high-pressure homogenization. The stabilizers were selected based on the saturation solubility and IVM stability within 72 h. The screening of formulations was performed by considering the drug content within the nanosize range. The best formulation (IVM:T80:PVP 1:0.5:0.5 wt%) was characterized in terms of the particle size distribution, morphology, crystallinity, drug content, and in vitro dissolution profile. This NS was also evaluated from a stability point of view, by conditioning samples at a constant temperature and relative humidity for six months. The fresh and conditioned best NSs Z-sizes were 174.6 and 215.7 nm, respectively; while both NSs showed low polydispersity indexes. The faster dissolution rate for the IVM NS was attributed to the presence of nanoparticles and changes to the crystal structure (i.e. amorphization) that further improved solubility. The best NS had a 4-fold faster initial dissolution rate than raw IVM, and is thus a promising formulation for the treatment of human and animal parasitic diseases.

Surface decoration of magnetic nanoparticles with folate-conjugated poly(N-isopropylacrylamide-co-itaconic acid): A facial synthesis of dual-responsive nanocarrier for targeted delivery of doxorubicin

ABSTRACTThe aim of study was to develop a novel drug nanocarrier via facile coating of a folate-conjugated dual-responsive copolymer with carboxylic functional groups on the surface of magnetic nanoparticles for the efficient loading and cell-specific targeting of a positively charged anticancer agent. The nanocarrier exhibited many favorable capabilities such as narrow distributed nano-ranged size (∼30 nm), high drug loading capacity (∼65%), and stimuli-responsive drug release. The results of various cell cytotoxicity studies such as MTT assay, DAPI staining, and flow cytometry concluded that the developed smart nanocarrier paves a way for efficient cancer therapy by the multiple targeting strategies.

Systematic development of solid self-nanoemulsifying oily formulations (S-SNEOFs) for enhancing the oral bioavailability and intestinal lymphatic uptake of lopinavir

The present studies entail the development of the systematically optimized solid self-nanoemulsifying oily formulations (S-SNEOFs) for enhancing the systemic bioavailability of lopinavir and targeting the same to the sanctuary site, i.e., lymphatic system for complete HIV inhibition. The patient-centric quality target product profile (QTPP) was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies, carried out through failure mode and effect critically analysis (FMECA), helped in identifying the plausible risks or failure modes affecting the quality attributes of the drug product. As per the preliminary studies, viz solubility and phase titration studies, and factor screening studies, Maisine (i.e., lipid), Tween 80 (emulgent), Transcutol HP (i.e., cosolvent) were selected as the critical material attributes (CMAs) of the liquid SNEOFs (L-SNEOFs). D-optimal mixture design was employed for the optimization of aforesaid CMAs and evaluated for in vitro dissolution, globule size, ex vivo permeation studies as the critical quality attributes (CQAs). Optimal composition of CMAs, was embarked through numerical optimization and desirability function, exhibited excellent permeation and drug release characteristics besides possessing globule size in nano range, i.e., 53.16nm. Further to increase the stability and drug loading, the OPT-L-SNEOFs were then adsorbed onto the porous carrier, i.e., Aeroperl, to prepare the OPT-SNEOF tablets which were finally compressed into the tablet employing MCC as the filler. The performance evaluation through in situ SPIP studies ascribed the significant enhancement in absorptivity parameters of both the SNEOFs vis-à-vis the pure drug. Also, chylomicron flow block SPIP studies revealed lymphatic uptake of lopinavir from the SNEOFs. Overall, in vivo pharmacokinetic studies in rats revealed significant improvement in the rate and extent of oral bioavailability of the SNEOFs compared to the pure drug. These studies further substantiate the intestinal lymphatic transport of lopinavir for the management of the sanctuary site HIV. In a nutshell, the SNEOFs offer a complete and holistic solution for the management of the viral loads in the lymph and blood.