Hydrophilic Matrix Research Articles

FORMULATION, EVALUATION AND OPTIMIZATION OF SUSTAINED-RELEASE DRUG DELIVERY SYSTEM OF CISAPRIDE TABLET

Objective: Cisapride is a novel prokinetic agent is best candidate for GERD. Cisapride 20 mg can be given thrice in a day given along with Proton pump inhibitor. By developing the sustain release formulation of Cisapride, the frequency of both drug can be reduce to once only to obtain good therapeutic response. Methods: Cisapride SR Tablets were prepared by direct compression technique with HPMC K4M and HPMC K100M polymers. Followed by various evaluation tests including in vitro disintegration and dissolution, the formulation was optimized by 32 full factorial designs with drug release kinetic analysis, compatibility studies (FTIR) and stability studies. Results: Results of Preformulation studies of the Cisapride indicate that it has poor flow property and compressibility property. To improve the flow and compressibility property, it was beneficial to use the directly compressible grade components in the formulation of tablet. Results of DSC study shown that there is no change in drug’s melting peak after the preparation of tablet. Hydrophilic matrix of HPMC K4M and HPMC K100M in combination sustained the Cisapride release effectively for more than 12h. The result indicates that the combination of HPMCK4M and HPMCK100M can be successfully, On the basis of the preliminary trials in the present study a32 full factorial design was employed to study the effect of independent variables, i.e. concentration of HPMCK4M(X1) and concentration of HPMCK100M(X2)on dependent variables like% drug release Q2, Q6 and Q10. Drug release is also dependent on the size of matrix tablets so, size and surface area was kept constant. Factorial batches F018, F019, F020, and F021 give the f2 value 75-100. Factorial batch F019 gives the highest f2 value 86.04 and also all the hour’s drug release was within the specified limits. Conclusion: The prepared formulation of Cisapride sustains release matrix tablet was stable and effective in treatment.

FORMULATION DEVELOPMENT AND EVALUATION OF MATRIX TABLET TRAZODONE HYDROCHLORIDE USING NATURAL POLYMER

Increased complications and costs of marketing of innovative drugs focused greater attention to the development of sustained release (SR) or controlled release (CR) drug delivery systems. Trazodone Hydrochloride (TRZ) is a well-known chemical compound that is used as an antidepressant that belongs to a selective serotonin reuptake inhibitor (SARI). The objective of present work was to develop and evaluated oral sustained release matrix tablet of TRZ. Pre-compression parameters were evaluated. The tablets were evaluated for post-compression parameters such as thickness, hardness, average weight, friability and In vitro release studies. No interactions were observed between TRZ and excipients from the Fourier transform infrared spectroscopy. The present research work was successful in improving the efficacy TRZ oral therapy as the drug release was extended for 12 hours thus reducing dosing frequency thereby improving patient compliance. The study also revealed the applicability of HPMC K-15, Gaur gum and PVP K30 as rate-controlling polymers in matrix tablets. The hydrophilic matrix of HPMC alone cannot control the release TRZ effective for 12 h while when combined with guar gum, may slow down the release of the drug and therefore, can be successfully employed for the formulation of matrix tablets SR. It may be concluded from the study that; the optimized formulation F-8 was shown maximum drug release 99.12 % in 12 h of dissolution. The release kinetic data of formulation F-8 shown first order release kinetics (R2 = 0.980).

Peptide-Polydopamine Nanocomposite Hydrogel for a Laser-Controlled Hydrophobic Drug Delivery.

Smart antibacterial systems, delivering antimicrobials in a highly controlled manner, are one strategy toward fighting the rise of antibiotic-resistant pathogens. Here, we engineer a laser-responsive antimicrobial nanocomposite hydrogel combining a peptide amphiphile and a photothermally active polydopamine nanoparticle (PDNP) to entrap the hydrophobic rifampicin within the hydrophilic hydrogel matrix. We show that the ability of the gelator to interact and retain rifampicin within the gel induced structural changes in its nanofiber network and mechanical properties. Furthermore, PDNP inclusion enabled laser-induced drug release, preventing growth of a Gram-negative E.coli. Overall, our work provides a significant advance in designing smart materials for controlled drug delivery applications.

Development of a Gastro-retentive Dosage Form of a New Promising Anti-tuberculosis Drug Macozinone

Introduction. Due to increase in the frequency of detecting cases of tuberculosis caused by strains of mycobacteria with resistance not only to traditional, but also recently introduced into clinical circulation anti-tuberculosis drugs, it is urgent to search for and develop new drugs that can be effective against multidrug-resistant (MDR-TB) and extensively drug resistant (XDR-TB) strains. One of the most promising classes of such compounds are fluorine derivatives of benzothiazinones, and particularly compound PBTZ169 (INN macozinone). This antibiotic has a high specificity against mycobacteria tuberculosis (M. tuberculosis), inhibiting one of the key enzymes of cell wall synthesis. However, macozinone as an active pharmaceutical ingredient has significant features of physical and chemical properties that hinder the development of oral dosage forms based on it. It is classified as class IV by BCS and is characterized by a very low solubility and lipophilicity, a pronounced dependence of dissolution rate on the pH of the medium, and very low bioavailability when taken orally.Aim. To substantiate the target profile, critical quality attributes and to develop a prototype of an oral dosage form with modified release of macozinone, allowing to maximize its pharmacological activity.Materials and methods. Using pharmaceutical substance macozinone hydrochloride and various excipients, experimental tablets with a dosage of 500 mg macozinone were developed. The influence of the composition of the media and the added excipients on the solubility of macozinone in various biorelevant media, the degree of swelling in the liquid and the degree of mucoadhesion of the experimental tablets to the mucus of the pig stomach were evaluated. The HPLC method was used to evaluate the kinetics of the release of the active substance.Results and discussion. In this work, the expediency of creating macozinone-containing gastro-retentive dosage forms with a slow release of the active substance, the delay mechanism of which is provided by swelling and increased adhesion to the gastric mucosa, has been substantiated. Various tablet samples were experimentally tested in which the modification of the release of the active substance and the degree of swelling and mucoadhesion were varied by introducing various excipients into the formulations, including known swelling and bioadhesive matrix agents.Conclusion. According to the results of the experiments, samples of high-dose (500 mg) swellable and mucoadhesive tablets created by the technology of two-stage granulation with the inclusion of macozinone - hydroxypropyl-beta-cyclodextrin mixtures in the primary granules and introduction of combinations of soluble and insoluble hydrophilic matrix agents into the intergranular space were recognized as the most promising for subsequent pharmacokinetic studies.

Cellulase as an “active” excipient in prolonged-release HPMC matrices: A novel strategy towards zero-order release kinetics

Hydrophilic matrices are of utmost interest for oral prolonged release of drugs. However, they show decreasing release rate over time, mainly due to lengthening of the diffusional pathway across the gel formed upon glass-rubber transition of the polymer. Therefore, achievement of zero-order release kinetics, which could reflect in constant drug plasma levels, is still an open issue. With the aim of improving the release performance of hydroxypropyl methylcellulose (HPMC) systems, the use of cellulolytic enzymes was proposed to aid erosion of the swollen matrix, thereby counteracting the release rate decrease particularly toward the end of the process. The effectiveness of this strategy was evaluated by studying the mass loss and drug tracer release from tableted matrices consisting of high-viscosity HPMC (Methocel® K4M), Acetaminophen and increasing amounts (0.5–10% on HPMC) of a cellulolytic product (Sternzym® C13030). A faster erosion and progressive shift to linearity of the overall release profiles were observed as a function of the enzyme concentration. Release was markedly linear from matrices containing 5 and 10% Sternzym® C13030. In partially coated matrices with these cellulase concentrations, such results were in agreement with data of erosion and swelling front movement, which exhibited early and long-lasting synchronization.

Active Carboxymethylcellulose-Based Edible Films: Influence of Free and Encapsulated Curcumin on Films' Properties.

Carboxymethylcellulose (CMC)-based films can act as a protective barrier in food surfaces and a carrier of bioactive compounds, such as curcumin. However, incorporating curcumin in hydrophilic matrixes can be a challenge, and new strategies need to be explored. In this work, CMC-based films containing free curcumin and curcumin-loaded nanohydrogels (composed of lactoferrin and glycomacropeptide) were produced and characterized. The incorporation of curcumin-loaded nanohydrogels showed a significant decrease in films’ thickness (from 0.0791 to 0.029 mm). Furthermore, the water vapor permeability of CMC-based films was significantly decreased (62%) by incorporating curcumin-loaded nanohydrogels in the films. The water affinity’s properties (moisture, solubility, and contact angle) of films were also affected by incorporating encapsulated curcumin. The addition of nanohydrogels to CMC-based films reduced the tensile strength values from 16.46 to 9.87 MPa. Chemical interactions were analyzed using Fourier transform infrared spectroscopy. The release profile of curcumin from CMC-based films was evaluated at 25 °C using a hydrophilic food simulant and suggests that the release mechanism of the curcumin happens by Fick’s diffusion and Case II transport. Results showed that protein-based nanohydrogels can be a good strategy for incorporating curcumin in edible films, highlighting their potential for use in food applications.

Gel Strength of Hydrophilic Matrix Tablets in Terms of In Vitro Robustness

PurposeThe purpose of this study was to correlate the gel strength of swollen matrix tablets with their in vitro robustness against agitation intensity and applied mechanical forces. Five commercial products, i.e. Glucophage®, Alfuzosin®, Tromphyllin®, Preductal® MR and Quetiapin® formulated as water-soluble/erodible matrix tablets were investigated.MethodsEffect of agitation speed (50–150 rpm) on drug release, hydration/erosion and gel strength was investigated using USP paddle apparatus II. The gel strength of matrix tablets during dissolution at different conditions was characterized by a texture analyzer.ResultsCommercial tablets formulated with HPMC of higher viscosity, such as K15M or K100M, demonstrated the gel strength in swollen state >0.02 MPa. In this case, the release mechanism was predominantly diffusional and, therefore, not affected by stirring speed and mechanical stress. In contrast, the Quetiapin® matrix tablet, formulated with HPMC K 4 M in amount of approx. 25%, demonstrated the gel strength dropped below 0.02 MPa after 6 h of release. In this case, the drug was predominantly released via erosional mechanism and very susceptible to stirring speed.ConclusionSufficient gel strength of swollen tablets is an important prerequisite for unchanged in vitro performance in consideration of mechanical stress.

Sustained Release Matrix Tablet: An Overview

Sustained Release is also a promising method for reducing medication side effects by preventing the therapeutic concentration of the drug from fluctuating in the body.The basic rationale of a sustained drug delivery system is to optimise a drug's biopharmaceutical, pharmacokinetic, and pharmacodynamic properties in order to maximise utility, minimise side effects, and cure the disease. The drug release rate is regulated by the matrix. HPMC and other release retardants can help with sustained release, so they are used as a key excipient in the formulation.The method entails compressing a mixture of medication, retardant material, and additives directly to shape a tablet with the drug embedded in a retardant matrix core; instead, granulation may be done prior to compression. Hydrophilic, hydrophobic, mineral, and biodegradable matrices may be used.To assess the drug release rate, in-vitro dissolution tests may be used. The primary goal of continuous release types is to improve drug therapy, which is determined by the relationship between the advantages and disadvantages of using one.

Long-Term Controlled Release of Simvastatin from Photoprinted Triple-Networked Hydrogels Composed of Modified Chitosan and PLA-PEG Micelles.

Local delivery of active agents using injectable or implantable hydrogels for tissue and bone regeneration is a promising therapy, but it remains challenging for controlling dose and duration of release. Simvastatin (SMV), a hydrophobic drug, has shown potential for osteogenic stimulation. Secure loading of hydrophobic drugs by physical interactions is particularly difficult to establish in hydrophilic polymer matrices, and their sustained release over several months for long-term regeneration has rarely been reported. Additionally, mechanical properties of hydrogels must be improved for a sufficient support while maintaining eventual biodegradability. This study assesses the effect of controlled SMV release from 3D-printed triple-network hydrogels for osteogenic stimulation and characterizes their mechanical and biological properties as an implant. SMV is loaded into polymeric micelles of polylactide/poly(ethylene glycol) triblock copolymers (PLA-PEG-PLA) and mixed with N-methacryloyl chitosan and PEG dimethacrylate to fabricate hydrogels by photo-cross-linked 3D printing. The hydrogel properties and drug release profiles have shown significant dependance on the polymer compositions. The SMV release from the triple-polymer-network hydrogel has continued for 17 weeks of observation. Cytocompatibility of hydrogels with various formulations is confirmed. The tunable triple-network hydrogels loaded with SMV provide a potential therapeutic value for bone regeneration.

Diazo-Based Copolymers for the Wet Strength Improvement of Paper Based on Thermally Induced CH-Insertion Cross-Linking.

We present an alternative to commonly used, but from an environmental point of view, problematic wet strength agents, which are usually added to paper to prevent a loss of mechanical stability and finally disintegrate when they get into contact with water. To this end, diazoester-containing copolymers are generated, which are coated onto paper and by heating to 110-160 °C for short periods of time become activated and form carbene intermediates, which undergo a CH-insertion cross-linking reaction. The process leads to a simultaneous cross-linking of the polymer and its attachment to the cellulose substrate. The immobilization process of copolymers consisting of a hydrophilic matrix based on N,N-dimethylacrylamide and a diazoester-based comonomer to a cellulose model surface and to laboratory-engineered, fibrous paper substrates is investigated as a function of time, temperature, and cross-linker composition. The distribution of the polymer in the fiber network is studied using confocal fluorescence microscopy. Finally, the tensile properties of modified wet and dry eucalyptus sulfate papers are measured to demonstrate the strong effect of the thermally cross-linked copolymers on the wet strength of paper substrates. Initial experiments show that the tensile indices of the modified and wetted paper samples are up to 50 times higher compared to the values measured for unmodified samples. When dry and wet papers coated with the above-described wetting agents are compared, relative wet strengths of over 30% are observed.

Biomimetic nanocomposite hydrogel networks for robust wet adhesion to tissues

Designing multifunctional medical adhesives with strong adhesiveness under water is of great significance to achieve desirable therapeutic effects for promoting wound healing. However, its design is still challenging since most of existing hydrogel adhesive cannot work in wet environments. Here we proposed a tissue adhesive made from a combination of hydrogel matrix and nanocrystal fillers. The adhesion mechanism of this hydrogel adhesive relies on the absorption of interfacial water from tissue surfaces by hydrophilic hydrogel matrix, while the nanocrystals from the hydration process of calcium sulphoaluminate (CSA) contributes to strong cohesion. Subsequent noncovalent and covalent bonds between amine groups on tissue surfaces and catechol groups on polydopamine-intercalated silicate nanoflakes (PDA-Silicate) further improves the adhesion ability. The hydrogel adhesive with optimal compositions exhibited robust adhesiveness to different surfaces, with over 30 kPa of adhesive strength to porcine skin under water. Furthermore, chopped curcumin-loaded electrospun nanofibers were added into the precursor with optimized formulation to form nanofibers/hydrogel composite (NF-HG) in situ. The obtained NF-HG exhibited enhanced antibacterial activity, sustained drug release and good cytocompatibility. Taken together, this strategy may open new route to design versatile functional underwater adhesives.

FORMATION OF NICKEL NANOPARTICLES IN SOLUTIONS OF A HYDROPHILIC GRAFT COPOLYMER

A graft copolymer of poly(vinyl alcohol) and polyacrylamide (PVA-g-PAAm) with interacting main and grafted chains was synthesized by radical matrix polymerization of PAAm from the PVA backbone in an aqueous medium. Its basic molecular parameters including the number and length (molecular weight) of grafts were determined using elemental analysis, DTGA and viscometry. The copolymer macromolecules formed special monomolecular micelles of elipsoidal shape and length ~18-64 nm in aqueous solutions due to the formation of intramolecular polycomplexes between the main and grafted chains. This copolymer was used as a hydrophilic matrix for the in situ synthesis of nickel nanoparticles (NiNPs) in aqueous solutions.On the basis of UV-Vis spectroscopy, an original and simple method for monitoring the kinetics of the formation and yield of metal nanoparticles in systems in which a surface plasmon resonance band does not appear has been proposed and implemented. Using this approach, the kinetics of borohydride reduction of Ni-salt to NiNPs in pure water and PVA-g-PAAm solutions was studied depending on the concentrations of Ni-salt and copolymer matrices. An increase in the initial rate of accumulation and yield of NiNPs with an increase in the concentration of Ni-salt and a decrease in both parameters in copolymer solutions in comparison with pure water was established. At the same time, the accumulation rate and NiNP yield in a complex way was depended on the matrix concentration that was determined by the ratio of such factors as a decrease in the diffusion rate of NaBH4 molecules in copolymer solutions and the accumulation of Ni2+-ions in matrix particles due to complexation with active chemical groups at the first stage of reduction process. The morphology and main structural elements of the NiNPs/PVA-g-PAAm composition were revealed using TEM. It was shown that the in situ synthesis of NiNPs in copolymer matrices was accompanied by the “detachment” of PAAm grafts from the main PVA chains and led to the appearance of two new structures, such as “hairy coils” and “hairy rods”, containing small spherical NiNPs (d~0,5–12,0 nm) in isolated and chain states, respectively. The appearance of the latter structures was explained by the formation of coordination complexes of Ni2+-ions with active groups of both PVA and PAAm chains at the first stage of the reduction reaction.

Thermoplastic Starch Nanocomposites Reinforced with Cellulose Nanocrystal Suspensions Containing Residual Salt from Neutralization

AbstractSulfuric acid‐catalyzed hydrolysis of cellulose commonly isolates cellulose nanocrystals (CNCs). Neutralizing the reactant solution with sodium hydroxide facilitates efficient downstream processing, but residual salt remains in the product. This study examines the reinforcing effects of CNCs from suspensions that contain residual salt on the mechanical properties of thermoplastic starch nanocomposites. By reinforcing starch films with up to 5 wt% CNCs, stiffness and strength are improved by 118% and 79%, respectively, indicating a good dispersion of CNCs in the starch matrix. Compared to nanocomposites incorporating salt‐free CNCs, the remaining salt has no significant impact on the material's mechanical performance. The results indicate great potential of CNCs containing residual salt as biobased, low‐cost nanofiller in hydrophilic polymer matrices.

Moisture-Wicking and Solar-Heated Coaxial Fibers with a Bark-like Appearance for Fabric Comfort Management.

Maintaining the human body's comfort is a predominant requirement of functional textiles, but there are still considerable drawbacks to design an intelligent textile with proper moisture absorption and evaporation properties. Herein, we develop moisture-wicking and solar-heated coaxial fibers with a bark-like appearance for fabric comfort management. The cortex layer of coaxial fibers can absorb moisture via the synergistic effect of the hierarchical roughness and the hydrophilic polymeric matrix. The core layer containing zirconium carbide nanoparticles can assimilate energy from the body and sunlight, which raises the surface temperature of the material and accelerates moisture evaporation. The resulting coaxial fiber-based membrane exhibits an excellent droplet diffusion radius of 2.73 cm, an excellent wicking height of 6.97 cm, and a high surface temperature of 61.7 °C which is radiated by simulated sunlight. Moreover, the designed fabric also exhibits a significant UV protection factor of 2000. Overall, the successful synthesis of such fascinating fibrous membranes enables the rapid removal of sweat from the human body textile, providing a suitable and comfortable microenvironment for the human body.

Development and Bio-Predictive Evaluation of Biopharmaceutical Properties of Sustained-Release Tablets with a Novel GPR40 Agonist for a First-in-Human Clinical Trial.

Sustained-release (SR) formulations may appear advantageous in first-in-human (FIH) study of innovative medicines. The newly developed SR matrix tablets require prolonged maintenance of API concentration in plasma and should be reliably assessed for the risk of uncontrolled release of the drug. In the present study, we describe the development of a robust SR matrix tablet with a novel G-protein-coupled receptor 40 (GPR40) agonist for first-in-human studies and introduce a general workflow for the successful development of SR formulations for innovative APIs. The hydrophilic matrix tablets containing the labeled API dose of 5, 30, or 120 mg were evaluated with several methods: standard USP II dissolution, bio-predictive dissolution tests, and the texture and matrix formation analysis. The standard dissolution tests allowed preselection of the prototypes with the targeted dissolution rate, while the subsequent studies in physiologically relevant conditions revealed unwanted and potentially harmful effects, such as dose dumping under an increased mechanical agitation. The developed formulations were exceptionally robust toward the mechanical and physicochemical conditions of the bio-predictive tests and assured a comparable drug delivery rate regardless of the prandial state and dose labeled. In conclusion, the introduced development strategy, when implemented into the development cycle of SR formulations with innovative APIs, may allow not only to reduce the risk of formulation-related failure of phase I clinical trial but also effectively and timely provide safe and reliable medicines for patients in the trial and their further therapy.

Cellular Antioxidant Effects and Bioavailability of Food Supplements Rich in Hydroxytyrosol

The present study evaluates the effect of olive (Olea europaea L.) vegetation water on human cells regarding its antioxidant properties and radical scavenger bioactivities. To this aim, two food supplements containing concentrated olive water in combination with 6% lemon juice or 70% grape juice, respectively, were assessed in different oxidation assays. From the investigated polyphenols, hydroxytyrosol, present in olives and in a lesser extent in grapes, was found to be the most abundant in both formulations, followed by tyrosol and oleuropein for the olive-derived concentrate with lemon juice, and by proanthocyanidins and tyrosol for the olive concentrate with grape juice. Cellular studies suggest that both formulations are effective antioxidants. In particular, the combination of olive and grape extracts showed a remarkable superoxides-, hydroxyl radicals-, and hydrogen peroxides-scavenging activity, while the formulation containing 94% olive concentrate wasmore potent in protecting the cells against lipoxidation. Both products showed a significant and similar effect in preventing advanced glycation end products’ (AGEs) formation. In addition, preliminary data indicate that hydroxytyrosol is absorbed into the human body when administered via these hydrophilic matrices, as confirmed by the urinary excretion of free hydroxytyrosol. Since the availability of phytochemicals largely depends on the vehicle in which they are solved, these findings are of relevance and contribute to supporting the healthful effects here assessed in a cellular environment.

Rapid, sensitive, and reliable quantitation of nicotine and its main metabolites cotinine and trans-3′-hydroxycotinine by LC-MS/MS: Method development and validation for human plasma

New nicotine delivery products are gaining market share. For evaluation of their characteristics, toxicokinetic investigations are in current research focus. For reliable determination of blood plasma levels of nicotine and its main metabolites cotinine and trans-3′-hydroxycotinine, a quantitation method based on LC-ESI-MS/MS was developed and validated. Addition of isotope labeled internal standards prior to rapid sample preparation using protein precipitation with methanol was chosen for sample preparation. Different stationary phases were tested and phenyl-hexyl separation was found to be superior to HILIC, C18, and C8 stationary phases. Ion suppression effects caused by hydrophilic early eluting matrix were eliminated by the adjustment of an adequate retention utilizing a phenyl-hexyl separation stationary phase. Exchange of acetonitrile as organic mobile phase by methanol and elevation of pH value of aqueous mobile phase containing 5 mM NH4Ac to 4.50 improved the chromatographic resolution. The limits of quantitation for nicotine, cotinine, and hydroxycotinine were 0.15, 0.30, and 0.40 ng/mL, respectively. Linearity was proven by matrix matched calibration for the whole working range from 0.50 ng/mL to 35.0 ng/mL for nicotine and from 6.00 to 420 ng/mL for cotinine and hydroxycotinine (Mandel’s fitting test with R2 > 0.995). Quality control samples at four different levels (0.50, 1.50, 17.5, 28.0 ng/mL for nicotine and 6.00, 18.0, 210, 336 ng/mL for cotinine and hydroxycotinine) in plasma were analyzed six times on three days. Mean accuracies ranged from 87.7% to 105.8% for nicotine, from 90.3% to 102.9% for cotinine, and from 99.9% to 109.9% for hydroxycotinine. Intra- and inter-day precisions (RSD %) were below 15% for all analytes (<20% for LLOQ). As proof of concept, the method was successfully applied to a real plasma sample from a cigarette smoking volunteer.

COMPATIBILITY SCREENING OF VIDAGLIPTIN WITH IONIC AND NON-IONIC POLYMERIC EXCIPIENTS FOR THE DESIGN OF EXTENDED RELEASE DELIVERY SYSTEM

Studies of drug-polymer compatibility play an important role in the preformulation stage for the development of pharmaceutical dosage forms. The potential physical and chemical interactions between drugs and polymer can affect the chemical nature, stability and bioavailability of the dosage form and as a result in the therapeutic response in the clinical phase. The present study reveals the thermal and spectroscopic study of physical mixtures of Vildagliptin (VDG) and HPMC in combination with cationic polymers chitosan, anionic polymers NaCMC and nonionic polymers PEO for extended release (ER). In the first phase of the study, differential scanning calorimeter (DSC) was used as tool to detect any interaction. In the next phase, a Fourier Transform Infrared Spectroscopy (FT-IR) technique was used to confirm and to investigate the type of the possible interactions between the components. In both cases, the spectroscopic data revealed that the analysed polymeric excipients did not show any affect on the VDG. Results of the present study indicated the suitability of the HPMC K4M hydrophilic matrix polymers in combination with cationic polymers, anionic polymers and non-ionic polymers in the preparation of extended release formulation of VDG.

Anti-Tim4 Grafting Strongly Hydrophilic Metal-Organic Frameworks Immunoaffinity Flake for High-Efficiency Capture and Separation of Exosomes.

Exosomes have become the most ideal analysis target for liquid biopsy since they carry a large amount of genetic materials. The study on exosomes has great significance for cancer diagnosis and prognosis. However, the extremely low concentration renders the development of a robust exosomes enrichment technique, with the merits of low nonspecific cell adhesion, high-capture efficiency, and easy nondestructive release of captured exosomes, of vital significance. We successfully designed and developed a novel Tim4@ILI-01 immunoaffinity flake material. First, a strongly hydrophilic ILI-01 MOFs matrix material was fabricated with cationic ionic liquid 1,3-bis(4-carboxybutyl)imidazolium bromide as the organic ligand. The nonspecific adsorption of the ILI-01 MOFs material was only 0.7% after two washings with a neutral buffer. Moreover, based on the inherent abundant carboxyl groups on the ILI-01 MOFs flake, they can be facilely functionalized with an anti-Tim4 antibody with the bonding efficiency of 82.4%. The capture efficiency of the developed Tim4@ILI-01 immunoaffinity material for exosomes reached 85.2%, which is 5.2 times higher than that via the gold standard ultracentrifugation method. Furthermore, based on the Ca2+-dependent characteristic of the binding between the Tim4@ILI-01 immunoaffinity material and phosphatidylserine (PS) on the surfaces of exosomes, the captured exosomes can be easily released with the addition of a chelating agent under neutral eluent conditions. Thus, the captured exosomes maintained good biological activity. The developed Tim4@ILI-01 immunoaffinity flake was successfully applied for enrichment of exosomes from serums of healthy persons and lung adenocarcinoma patients. The levels of the expressed CD44 gene significantly changed under different stages of lung adenocarcinoma cancer. All these results demonstrate that the Tim4@ILI-01 immunoaffinity flake is a robust enrichment material and has a good potential in practical clinical applications.

POLYMER BIOCOMPOSITES BASED ON AGRO WASTE: PART I. SOURCE, CLASSIFICATION, CHEMICAL COMPOSITION AND TREATMENT METHODS OF LIGNOCELLULOSIC NATURAL FIBERS

At present, the depletion of natural resources and environmental problems have generated great interest in finding a sustainable alternative to create new materials that are environmentally friendly. In recent years, many researchers have focused on investigations related to agricultural waste products to solve environmental problems associated with the disposal of agro waste. Thanks to their annual renewability and biodegradability, over the past two decades, agricultural waste has become an environmentally friendly alternative to synthetic fibers. In this regard, this review gives a general idea of new lignocellulosic polymer composite materials in which various natural fibers are used as fillers and reinforcing additives. The sources, classification and chemical composition of lignocellulosic natural fibers have been also given. Natural fibers include a hydroxyl functional group that makes the fibers hydrophilic. Hydrophilic natural fibers and hydrophobic polymer matrix lead to incompatibility and weak interfacial bonds between them. To resolve the problem of incompatibility of plant fibers with non-polar polymer matrices, various methods of surface treatment of natural fibers, including physical, chemical and biological processing, have been considered. From this perspective, in our opinion, the data presented in this article can be used as a database for further study of agricultural waste as fillers or reinforcing additives in polymer composites in order to accelerate the development and stimulate the commercial production of these new materials.