Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs.

This manuscript offers a comprehensive overview of nanotechnology's impact on the solubility and bioavailability of poorly soluble drugs, with a focus on BCS Class II and IV drugs. We explore various nanoscale drug delivery systems (NDDSs), including lipid-based, polymer-based, nanoemulsions, nanogels, and inorganic carriers. These systems offer improved drug efficacy, targeting, and reduced side effects. Emphasizing the crucial role of nanoparticle size and surface modifications, the review discusses the advancements in NDDSs for enhanced therapeutic outcomes. Challenges such as production cost and safety are acknowledged, yet the potential of NDDSs in transforming drug delivery methods is highlighted. This contribution underscores the importance of nanotechnology in pharmaceutical engineering, suggesting it as a significant advancement for medical applications and patient care.

Effect of electron beam irradiation pretreatment and different fatty acid types on the formation, structural characteristics and functional properties of starch-lipid complexes.

The effects of different electron beam irradiation doses (2, 4, 8 KGy) and various types of fatty acids (lauric acid, stearic acid, and oleic acid) on the formation, structure, physicochemical properties, and digestibility of starch-lipid complex were investigated. The complexing index of the complexes was higher than 85 %, indicating that the three fatty acids could easily form complexes with starch. With the increase of electron beam irradiation dose, the complexing index increased first and then decreased. The highest complexing index was lauric acid (97.12 %), stearic acid (96.80 %), and oleic acid (97.51 %) at 2 KGy radiation dose, respectively. Moreover, the microstructure, crystal structure, thermal stability, rheological properties, and starch solubility were analyzed. In vitro digestibility tests showed that adding fatty acids could reduce the content of hydrolyzed starch, among which the resistant starch content of the starch-oleic acid complex was the highest (54.26 %). The lower dose of electron beam irradiation could decrease the digestibility of starch and increase the content of resistant starch.

Detailed structural characterization of five water-insoluble α-glucans produced by glucansucrases from Streptococcus spp.

Water-insoluble α-glucans synthesized from sucrose by glucansucrases from Streptococcus spp. are essential in dental plaque and caries formation. Because limited information is available on the fine structure of these biopolymers, we analyzed the structures of unmodified glucans produced by five recombinant Streptococcus (S.) mutans DSM 20523 and S. salivarius DSM 20560 glucansucrases in detail. A combination of methylation analysis, endo-dextranase and endo-mutanase hydrolyses, and HPSEC-RI was used. Furthermore, crystal-like regions were analyzed by using XRD and 13C MAS NMR spectroscopy. Our results showed that the glucan structures were highly diverse: Two glucans with 1,3- and 1,6-linkages were characterized in detail besides an almost exclusively 1,3-linked and a linear 1,6-linked glucan. Furthermore, one glucan contained 1,3-, 1,4-, and 1,6-linkages and thus had an unusual, not yet described structure. It was demonstrated that the glucans had a varying structural architecture by using partial enzymatic hydrolyses. Furthermore, crystal-like regions formed by 1,3-glucopyranose units were observed for the two 1,3- and 1,6-linked glucans and the linear 1,3-linked glucan. 1,6-linked regions were mobile and not involved in the crystal-like areas. Altogether, our results broaden the knowledge of the structure of water-insoluble α-glucans from Streptococcus spp.

Optimizing Process Parameters for Controlled Drug Delivery: A Quality by Design (QbD) Approach in Naltrexone Microspheres.

The formulation of microspheres involves a complex manufacturing process with multiple steps. Identifying the appropriate process parameters to achieve the desired quality attributes poses a significant challenge. This study aims to optimize the critical process parameters (CPPs) involved in the preparation of naltrexone microspheres using a Quality by Design (QbD) methodology. Additionally, the research aims to assess the drug release profiles of these microspheres under both in vivo and in vitro conditions. Critical process parameters (CPPs) and critical quality attributes (CQAs) were identified, and a Box-Behnken design was utilized to delineate the design space, ensuring alignment with the desired Quality Target Product Profile (QTPP). The investigated CPPs comprised polymer concentration, aqueous phase ratio to organic phase ratio, and quench volume. The microspheres were fabricated using the oil-in-water emulsion solvent extraction technique. Analysis revealed that increased polymer concentration was correlated with decreased particle size, reduced quench volume resulted in decreased burst release, and a heightened aqueous phase ratio to organic phase ratio improved drug entrapment. Upon analyzing the results, an optimal formulation was determined. In conclusion, the study conducted in vivo drug release testing on both the commercially available innovator product and the optimized test product utilizing an animal model. The integration of in vitro dissolution data with in vivo assessments presents a holistic understanding of drug release dynamics. The QbD approach-based optimization of CPPs furnishes informed guidance for the development of generic pharmaceutical formulations.

Theory of 2D electronic spectroscopy of water soluble chlorophyll-binding protein (WSCP): Signatures of Chl b derivate.

We investigate how electronic excitations and subsequent dissipative dynamics in the water soluble chlorophyll-binding protein (WSCP) are connected to features in two-dimensional (2D) electronic spectra, thereby comparing results from our theoretical approach with experimental data from the literature. Our calculations rely on third-order response functions, which we derived from a second-order cumulant expansion of the dissipative dynamics involving the partial ordering prescription, assuming a fast vibrational relaxation in the potential energy surfaces of excitons. Depending on whether the WSCP complex containing a tetrameric arrangement of pigments composed of two dimers with weak excitonic coupling between them binds the chlorophyll variant Chl a or Chl b, the resulting linear absorption and circular dichroism spectra and particularly the 2D spectra exhibit substantial differences in line shapes. These differences between Chl a WSCP and Chl b WSCP cannot be explained by the slightly modified excitonic couplings within the two variants. In the case of Chl a WSCP, the assumption of equivalent dimer subunits facilitates a reproduction of substantial features from the experiment by the calculations. In contrast, for Chl b WSCP, we have to assume that the sample, in addition to Chl b dimers, contains a small but distinct fraction of chemically modified Chl b pigments. The existence of such Chl b derivates has been proposed by Pieper et al. [J. Phys. Chem. B 115, 4042 (2011)] based on low-temperature absorption and hole-burning spectroscopy. Here, we provide independent evidence.

Optimization of Hypericum Perforatum Microencapsulation Process by Spray Drying Method.

Hypericum perforatum (HP) contains valuable and beneficial bioactive compounds that have been used to treat or prevent several illnesses. Encapsulation technology offers protection of the active compounds and facilitates to expose of the biologically active compounds in a controlled mechanism. Microcapsulation of the hydroalcoholic gum arabic and maltodextrin have hot been used as wall materials in the encapsulation of HP extract. Therefore, the optimum microencapsulation parameters of Hypericum perforatum (HP) hydroalcoholic extract were determined using response surface methodology (RSM) for the evaluation of HP extract. Three levels of three independent variables were screened using the one-way ANOVA. Five responses were monitored, including total phenolic content (TPC), 2,2-Diphenyl-1-picrylhydrazyl (DPPH), carr index (CI), hausner ratio (HR), and solubility. Optimum drying conditions for Hypericum perforatum microcapsules (HPMs) were determined: 180 °C for inlet air temperature, 1.04/1 for ratio of maltodextrin to gum arabic (w/w), and 1.98/1 for coating to core material ratio (w/w). TPC, antioxidant activity, CI, HR, and solubility values were specified as 316.531 (mg/g GAE), 81.912%, 6.074, 1.066, and 35.017%, respectively, under the optimized conditions. The major compounds of Hypericum perforatum (hypericin and pseudohypericin) extract were determined as 4.19 µg/g microcapsule and 15.09 µg/g microcapsule, respectively. Scanning electron microscope (SEM) analysis revealed that the mean particle diameter of the HPMs was 20.36 µm. Based on these results, microencapsulation of HPMs by spray drying is a viable technique which protects the bioactive compounds of HP leaves, facilitating its application in the pharmaceutical, cosmetic, and food industries.

Efficient production of human interleukin-3 from Escherichia coli using protein disulfide isomerase b'a' domain.

Human interleukin-3 (IL3) is a multifunctional cytokine essential for both clinical and biomedical research endeavors. However, its production in Escherichia coli has historically been challenging due to its aggregation into inclusion bodies, requiring intricate solubilization and refolding procedures. This study introduces an innovative approach employing two chaperone proteins, maltose binding protein (MBP) and protein disulfide isomerase b'a' domain (PDIb'a'), as N-terminal fusion tags. Histidine tag (H) was added at the beginning of each chaperone protein gene for easy purification. This fusion of chaperone proteins significantly improved IL3 solubility across various E. coli strains and temperature conditions, eliminating the need for laborious refolding procedures. Following expression optimization, H-PDIb'a'-IL3 was purified using two chromatographic methods, and the subsequent removal of the H-PDIb'a' tag yielded high-purity IL3. The identity of the purified protein was confirmed through liquid chromatography coupled with tandem mass spectrometry analysis. Biological activity assays using human erythroleukemia TF-1 cells revealed a unique two-step stimulation pattern for both purified IL3 and the H-PDIb'a'-IL3 fusion protein, underscoring the protein's functional integrity and revealing novel insights into its cellular interactions. This study advances the understanding of IL3 expression and activity while introducing novel considerations for protein fusion strategies.

Effect of dual modifications with ultrasonication and succinylation on Cicer arietinum protein-iron complexes: Characterization, digestibility, in-vitro cellular mineral uptake and preparation of fortified smoothie.

The research aimed to evaluate the effect of ultrasonication and succinylation on the functional, iron binding, physiochemical, and cellular mineral uptake efficacy of chickpea protein concentrate. Succinylation resulted in significant improvements in the water-holding capacity (WHC) (25.47 %), oil-holding capacity (OHC) (31.38 %), and solubility (5.80 %) of the chickpea protein-iron complex. Mineral bioavailability significantly increased by 4.41 %, and there was a significant increase in cellular mineral uptake (64.64 %), retention (36.68 %), and transport (27.96 %). The ferritin content of the succinylated chickpea protein-iron complex showed a substantial increase of 66.31%. Furthermore, the dual modification approach combining ultrasonication and succinylation reduced the particle size of the protein-iron complex with a substantial reduction of 83.25 %. It also resulted in a significant enhancement of 51.5 % in the SH (sulfhydryl) content and 48.92 % in the surface hydrophobicity. Mineral bioavailability and cellular mineral uptake, retention, and transport were further enhanced through dual modification. In terms of application, the addition of single and dual-modified chickpea protein-iron complex to a fruit-based smoothie demonstrated positive acceptance in sensory attributes. Overall, the combined approach of succinylation and ultrasonication to the chickpea protein-iron complex shows a promising strategy for enhancing the physiochemical and techno-functional characteristics, cellular mineral uptake, and the development of vegan food products.

Self Emulsifying Delivery System of Cissus quadrangularis: Evidence of Enhanced Efficacy and Promising Pharmacokinetic Profile in the Management of Osteoporosis.

Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.

Conventional vs Mechanistic IVIVC: A Comparative Study in Establishing Dissolution Safe Space for Extended Release Formulations.

The use of in vitro-in vivo correlation (IVIVC) for extended release oral dosage forms is an important technique that can avoid potential clinical studies. IVIVC has been a topic of discussion over the past two decades since the inception of USFDA guidance. It has been routinely used for biowaivers, establishment of dissolution safe space and clinically relevant dissolution specifications, for supporting site transfers, scale-up and post approval changes. Although conventional or mathematical IVIVC is routinely used, other approach such as mechanistic IVIVC can be of attractive choice as it integrates all the physiological aspects. In the present study, we have performed comparative evaluation of mechanistic and conventional IVIVC for establishment of dissolution safe space using divalproex sodium and tofacitinib extended release formulations as case examples. Conventional IVIVC was established using Phoenix and mechanistic IVIVC was set up using Gastroplus physiologically based biopharmaceutics model (PBBM). Virtual dissolution profiles with varying release rates were constructed around target dissolution profile using Weibull function. After internal and external validation, the virtual dissolution profiles were integrated into mechanistic and conventional IVIVC and safe space was established by absolute error and T/R ratio's methods. The results suggest that mechanistic IVIVC yielded wider safe space as compared to conventional IVIVC. The results suggest that a mechanistic approach of establishing IVIVC may be a flexible approach as it integrates physiological aspects. These findings suggest that mechanistic IVIVC has wider potential as compared to conventional IVIVC to gain wider dissolution safe space and thus can avoid potential clinical studies.

Comparative evaluation of dissolution profiles of the generic drug lamivudine 150 mg tablet marketed in Peru vs. the innovative Epivir. / Evaluación comparativa de perfiles de disolución del medicamento genérico lamivudina tableta 150 mg comercializado en Perú frente al innovador Epivir.

Lamivudine is one of the most prescribed drugs in the world, and is used to treat human immunodeficiency and hepatitis B. This study aimed to evaluate the quality attributes and compare the dissolution profiles of two batches (A and B) of generic lamivudine 150 mg tablets with the innovator drug Epivir 150 mg tablets. We conducted an analytical, experimental, cross-sectional study, and used a spectrophotometric method at a wavelength of maximum absorption (λ) corresponding to 270 nm, to measure the percentage of dissolved drug. The study evaluated identification, content, dissolution and mass uniformity. Apparatus 2 USP (Paddle) 75 rpm, 900 mL of dissolution medium (37 ± 0.5 °C) was used in three dissolution media: pH 1.2; 4.5 and 6.8. Samples of 5 mL were obtained at 5, 10, 15, 20 and 30 min. Both batches of generic lamivudine (A and B) were found to have the same dissolution kinetic profile as the innovator drug. Both formulations met the criteria of very fast dissolving (85% dissolved in 15 min), and fast dissolving (85% dissolved in 30 min) drugs. Therefore, it was not necessary to calculate the similarity factor. We concluded that generic drugs A and B are in vitro equivalents to the innovator drug Epivir. Motivation for the study. To evaluate the quality of antiretroviral drugs used in the treatment of HIV dispensed in the HAART Program of the Ministry of Health of Peru. Main findings. Two batches of generic lamivudine drugs were found to achieve a dissolution rate greater than 85% at 15 min, being equivalent in vitro to the reference product Epivir. Implications. There is a need to apply the current regulations regarding equivalence between drugs by the regulatory authority prior to their authorization and to include dissolution profile tests as a requirement in public drug purchases, especially in national strategies (HIV, TB, etc.), in order to ensure quality products for the population.

La lamivudina es uno de los medicamentos más prescritos en el mundo, se utiliza para tratar la inmunodeficiencia humana y la hepatitis B. El objetivo del estudio fue evaluar los atributos de calidad y comparar los perfiles de disolución de dos lotes (A y B) del medicamento genérico lamivudina 150 mg tabletas con el medicamento innovador Epivir 150 mg tabletas. Se realizó un estudio analítico, experimental y de corte transversal, se usó un método espectrofotométrico a una longitud de onda de máxima absorción (λ) correspondiente a 270 nm, para medir el porcentaje de fármaco disuelto. El estudio evaluó identificación, contenido, disolución y uniformidad de masas. Se usó el aparato 2 USP (Paleta) 75 rpm, 900 mL de medio de disolución (37 ± 0,5 °C) a en tres medios de disolución: pH 1,2; 4,5 y 6,8. Se retiraron muestras de 5 mL a los 5, 10, 15, 20 y 30 min. Se encontró que ambos lotes de lamivudina genérico (A y B) presentan el mismo perfil cinético de disolución que el medicamento innovador. Ambas formulaciones cumplen con el criterio de medicamentos de disolución muy rápida (85% disuelto en 15 min), y de disolución rápida (85% disuelto en 30 min). Por lo tanto, no fue necesario calcular el factor de similitud. Se concluye que los medicamentos genéricos A y B son equivalentes in vitro con el medicamento innovador Epivir. Motivación para realizar el estudio. Evaluar la calidad de los medicamentos antirretrovirales usados en el tratamiento del VIH dispensados en el Programa TARGA del Ministerio de Salud de Perú. Principales hallazgos. Se encontró que dos lotes de medicamentos genéricos de lamivudina alcanzaron un porcentaje de disolución mayor del 85% a los 15 min, siendo equivalentes in vitro al producto de referencia Epivir. Implicancias. Existe la necesidad de aplicar la normatividad vigente respecto a equivalencia entre fármacos por parte de la autoridad regulatoria previo a su autorización e incluir ensayos de perfil de disolución como requisito en las compras públicas de medicamentos, especialmente en las estrategias nacionales (VIH, TBC, etc.), con la finalidad de asegurar productos de calidad para la población.

Defining a Water-Soluble Formulation of Arachidonic Acid as a Novel Ferroptosis Inducer in Cancer Cells.

Here, we describe GS-9, a novel water-soluble fatty acid-based formulation comprising L-lysine and arachidonic acid, that we have shown to induce ferroptosis. GS-9 forms vesicle-like structures in solution and mediates lipid peroxidation, as evidenced by increased C11-BODIPY fluorescence and an accumulation of toxic malondialdehyde, a downstream product of lipid peroxidation. Ferroptosis inhibitors counteracted GS-9-induced cell death, whereas caspase 3 and 7 or MLKL knock-out cell lines are resistant to GS-9-induced cell death, eliminating other cell death processes such as apoptosis and necroptosis as the mechanism of action of GS-9. We also demonstrate that through their role of sequestering fatty acids, lipid droplets play a protective role against GS-9-induced ferroptosis, as inhibition of lipid droplet biogenesis enhanced GS-9 cytotoxicity. In addition, Fatty Acid Transport Protein 2 was implicated in GS-9 uptake. Overall, this study identifies and characterises the mechanism of GS-9 as a ferroptosis inducer. This formulation of arachidonic acid offers a novel tool for investigating and manipulating ferroptosis in various cellular and anti-cancer contexts.

Structure, thermal stability, physicochemical and functional characteristics of insoluble dietary fiber obtained from rice bran with steam explosion treatment: Effect of different steam pressure and particle size of rice bran.

Rice bran was modified by steam explosion (SE) treatment to investigate the impact of different steam pressure (0.4, 0.8, 1.2, 1.6, and 2.0 MPa) with rice bran through 60 mesh and rice bran pulverization (60, 80, and 100 mesh) with the steam pressure of 1.2 MPa on the structure, thermal stability, physicochemical and functional characteristics of insoluble dietary fiber (IDF) extracted from rice bran. IDF with SE treatment from scanning electron microscopy images showed a porous honeycomb structure, and lamellar shape in IDF became obvious with the increase of steam pressure. The relative crystallinity and polymerization degree of crystalline regions in IDF from rice bran with SE treatment from X-ray diffraction analysis were decreased. Differential scanning calorimetry results showed that thermal stability of IDF with SE treatment increased with the increase of crushing degree. The results of FT-IR also suggested that some glycosidic and hydrogen bonds in IDF could be broken, and some cellulose and hemicellulose were degraded during SE process. The physicochemical and functional characteristics of IDF, including water-holding capacity, oil-holding, glucose adsorption capacity, α-amylase and pancreatic lipase inhibition capacity were decreased with the increase of steam pressure and crushing degree. The swelling and nitrite adsorption capacities of IDF were increased first and then decreased with the increase of steam pressure. The physicochemical and functional characteristics of IDF from rice bran were improved after SE treatment, which might provide references for the utilization of IDF from rice bran with SE treatment.

The impact of extraction processes on the physicochemical, functional properties and structures of bamboo shoot protein.

This study aimed to extract bamboo shoot protein (BSP) using different extraction approaches and compare their functional and physicochemical properties with commercial protein ingredients, including whey protein and soy protein isolates. The extraction methods including alkali extraction (AE), salt extraction (SE), and phosphate-aided ethanol precipitation (PE) were used. An enhanced solvent extraction method was utilized in combination, resulting in a significant improvement in the protein purity, which reached 81.59 %, 87.36 %, and 67.08 % respectively. The extraction methods had significant effects on the amino acid composition, molecular weight distribution, and functional properties of the proteins. SE exhibited the best solubility and emulsification properties. Its solubility reached up to 93.38 % under alkaline conditions, and the emulsion stabilized by SE with enhanced solvent extraction retained 60.95 % stability after 120 min, which could be attributed to its higher protein content, higher surface hydrophobicity, and relative more stable and organized protein structure. All three BSP samples demonstrated better oil holding capacity, while the SE sample showed comparable functional properties to soy protein such as foaming and emulsifying properties. These findings indicate the potential of BSP as an alternative plant protein ingredient in the food industry.

Effects of molecular structure and charge state on the foaming and emulsifying properties of Spirulina protein isolates.

Microalgae protein holds great potential for various applications in the food industry. However, the current knowledge regarding microalgae protein remains limited, with little information available on its functional properties. Furthermore, the relationship between its molecular structure and functional properties is not well defined, which limits its application in food processing. This study aims to addresses these gaps though an analysis of the emulsibility and foamability of various soluble protein isolates from two species of Spirulina (Arthospira platensis and Spirulina platensis), and the functional properties of Spirulina protein isolates in relation to its molecular structure and charge state. Results revealed that the degree of cross-linking and aggregation or folding and curling of protein tertiary structures was higher in the highly soluble Spirulina protein isolates (AP50% and SP50%) than in the low-solubility isolates (AP30% and SP30%). The foaming capacity (FC) of AP50% and SP50% was found to be lower than that of AP30% and SP30%. Spirulina protein isolates can stably adsorb at the air-water interface for at least 20 min and possessed good interfacial activity. A high pH value was found to promote cross-linking of protein particles at the oil-water interface, thereby reinforcing the internal network structure of emulsions and increasing viscosity. These findings provide preliminary insights for potential applications of Spirulina protein isolates in food production, especially towards quality improvement.

Plant and animal protein mixed systems as wall material for microencapsulation of Manuka essential Oil: Characterization and in vitro release kinetics.

Combination of plant and animal protein diet is becoming a valuable source of nutrition in the modern diet due to the synergistic functional properties inherent in these protein complexes. Moreover, the synergy between animal and plant proteins can contribute to the high stability and improved solubility of the encapsulated bioactive ingredients (e.g., essential oils). Therefore, the study was designed to evaluate the plant (pea protein (PP) and lupine protein (LP)) and animal protein (whey protein, WP) mixed systems as a wall material for microencapsulation of manuka essential oil, as an example of bioactive compound. Moreover, physicochemical properties and in vitro release profile of encapsulated manuka essential oil were studied. Manuka essential oil microcapsules exhibited low moisture content (5.3-7.1 %) and low water activity (0.33-0.37) with a solubility of 53.7-68.1 %. Change in wall material ratio significantly affected the color of microcapsules, while microcapsules prepared with 1:1 protein/oil ratio demonstrated a high encapsulation efficiency (90.4 % and 89.4 %) for protein mixed systems (PP + WP and LP + WP), respectively. Microcapsules further showed low values for lipid oxidation with a high oxidative stability and antioxidant activity (62.1-87.0 %). The zero order and Korsmeyer-Peppas models clearly explained the release mechanism of encapsulated oil, which was dependent on the type and concentration of the protein mixed used. The findings demonstrated that the protein mixed systems successfully encapsulated the manuka essential oil with controlled release and high oxidative stability, indicating the suitability of the protein mixed systems as a carrier in encapsulation and application potential in development of encapsulated functional foods.

Preparation and evaluation of fenbendazole methyl-ß-cyclodextrin inclusion complexes.

As an orally effective benzimidazole anthelmintic agent, fenbendazole was not only widely used in agriculture and animal husbandry to prevent and treat parasites, but also shows anti-cancer effects against several types of cancer, exhibits anti-cancer effects in paclitaxel and doxorubicin-resistant cancer cells. However, fenbendazole's poor in water solubility (0.3 µg/mL), limits its clinical applications. Even great efforts were made toward increasing its water solubility, the results were not significant to reach anti-cancer drug delivery requirement (5-10 mg/mL). Through single factor and orthogonal strategy, many complex conditions were designed and used to prepare the complexes, the inclusion complex with methyl-ß-cyclodextrin with 29.2 % of inclusion rate and 89.5% of inclusion yield can increase drug's water solubility to 20.21 mg/mL, which is the best result so far. Its structure was confirmed by differential scanning calorimetry, scanning electron microscopic image, 1D and 2D NMR spectra in D2O. In its in vitro pharmacokinetic study, fenbendazole was 75% released in 15 min., in its in vivo pharmacokinetic study, the bio-availabilities of fenbendazole, its major metabolic anthelmintic agent oxfendazole and its minor metabolic anthelmintic agent oxfendazole were increased to 138%, 149% and 169% respectively, which would allow for fewer drug doses to achieve the same therapeutic effect and suggest that the complex can be used as a potential anticancer agent.

Parenteral platforms for tunable, long-acting administration of a highly hydrophobic antiretroviral drug.

GSK2838232 (GSK8232) is a second-generation maturation inhibitor (MI) developed for the treatment of HIV with excellent broad-spectrum virological profiles. The compound has demonstrated promising clinical results as an orally administered agent. Additionally, the compound's physical and pharmacological properties present opportunities for exploitation as long-acting parenteral formulations. Despite unique design constraints including solubility and dose of GSK8232, we report on three effective tunable drug delivery strategies: active pharmaceutical ingredient (API) suspensions, ionic liquids, and subdermal implants. Promising sustained drug release profiles were achieved in rats with each approach. Additionally, we were able to tune drug release rates through a combination of passive and active strategies, broadening applicability of these formulation approaches beyond GSK8232. Taken together, this report is an important first step to advance long-acting formulation development for critical HIV medicines that do not fit the traditional profile of suitable long-acting candidates.

Deep eutectic solvent self-assembled reverse nanomicelles for transdermal delivery of sparingly soluble drugs.

BACKGROUND: Transdermal delivery of sparingly soluble drugs is challenging due to their low solubility and poor permeability. Deep eutectic solvent (DES)/or ionic liquid (IL)-mediated nanocarriers are attracting increasing attention. However, most of them require the addition of auxiliary materials (such as surfactants or organic solvents) to maintain the stability of formulations, which may cause skin irritation and potential toxicity. RESULTS: We fabricated an amphiphilic DES using natural oxymatrine and lauric acid and constructed a novel self-assembled reverse nanomicelle system (DES-RM) based on the features of this DES. Synthesized DESs showed the broad liquid window and significantly solubilized a series of sparingly soluble drugs, and quantitative structure-activity relationship (QSAR) models with good prediction ability were further built. The experimental and molecular dynamics simulation elucidated that the self-assembly of DES-RM was adjusted by noncovalent intermolecular forces. Choosing triamcinolone acetonide (TA) as a model drug, the skin penetration studies revealed that DES-RM significantly enhanced TA penetration and retention in comparison with their corresponding DES and oil. Furthermore, in vivo animal experiments demonstrated that TA@DES-RM exhibited good anti-psoriasis therapeutic efficacy as well as biocompatibility. CONCLUSIONS: The present study offers innovative insights into the optimal design of micellar nanodelivery system based on DES combining experiments and computational simulations and provides a promising strategy for developing efficient transdermal delivery systems for sparingly soluble drugs.

A novel biopolymeric composite edible film based on sunnhemp protein isolate and potato starch incorporated with clove oil: Fabrication, characterization, and amino acid composition.

Composite edible films were developed by casting method using sunnhemp protein isolate (SHPI) and potato starch (PS) at various proportions (100:0, 90:10, 80:20; 70:30, 60:40, and 50:50) containing glycerol as a plasticizer and clove oil. All the edible films were evaluated for thickness, moisture content, solubility, swelling ratio, water activity. Further characterization of edible films was done on the basis of mechanical, optical, thermal and structural attributes along with morphology. Among all the films, composite film containing 50 % SHPI, 50 % PS and 1 % clove oil were having better characteristics. The solubility and WVP decreased, while the tensile strength and elongation at break of composite film increased with the inclusion of potato starch and clove oil. Intermolecular interactions in the composite film matrix were confirmed by FTIR and XRD analysis. SEM images confirmed the structural compactness and integrity of all the developed films. The amino acid composition of edible films indicated presence of most of the essential amino acids. The present finding of this research work shows that the utilization of sunnhemp protein in the development of biocomposite edible films represents an alternative opportunity of sustainable edible food packaging.