In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 μg 5-FU/g rat colon content vs 4.66 μg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach.
Polysaccharides are attracting the vigil eye of researchers in order to design the green synthesis of silver nanoparticles (Ag NPs) of diverse size, shape, and application. We report an environmentally friendly method to synthesize Ag NPs where no physical reaction conditions were employed. Hydroxypropylcellulose (HPC) was used as a template nanoreactor, stabilizer, and capping agent to obtain Ag NPs. Different concentrations of AgNO3 solutions (50 mmol, 75 mmol, and 100 mmol) were mixed with a concentrated aqueous solution of HPC and the progress of the reaction was monitored by noting color changes of the reaction mixture at different reaction times for up to 24 hours. Characteristic ultraviolet-visible spectroscopy (UV/Vis) absorption bands of Ag NPs were observed in the range of 388-452 nm. The morphology of the Ag NPs was studied by scanning electron microscopy, transmission electron microscopy (TEM), and atomic force microscopy. The TEM images confirmed that the size of the Ag NPs was in the range of 25-55 nm. Powder X-ray diffraction studies showed that the crystal phase of the Ag NPs was face-centered cubic. The as-prepared Ag NPs were found to be stable, and no changes in size and morphology were observed after storage in HPC thin films over 1 year, as indicated by UV/Vis spectra. So, the present work furnishes a green and economical strategy for the synthesis and storage of stable Ag NPs. As-synthesized Ag NPs showed significant antimicrobial activity against different bacterial (Escherichia coli, Staphylococcus epidermidis, S. aureus, Bacillus subtilis, Pseudomonas aeruginosa) and fungal strains (Actinomycetes and Aspergillus niger).
In this study, randomly oriented hydroxyethyl cellulose/polyvinyl alcohol (HEC/PVA) nanofibers were fabricated by electrospinning. The blend solutions of HEC/PVA with different weight ratio of HEC to PVA were prepared using water as solvent to fabricate nanofibers. These nanofibrous scaffolds were coated with bone-like apatite by immersing into 10x simulated body fluid (SBF) for different time periods. The morphology and structure of the nanofibers were characterized by SEM, FTIR and DSC. FESEM-EDS and FTIR analysis were used to confirm the deposition of apatite on the surface of nanofibers. The results of this study suggest that this apatite coated nanofibrous scaffolds could be a suitable biomaterial for bone tissue engineering.
Mebeverine HCl is a water soluble drug commonly used to treat irritable bowel syndrome by acting directly on the smooth muscles of the colon. This work was aimed at the formulation and in vitro evaluation of a colon-targeted drug delivery system containing mebeverine HCl. Matrix tablets were prepared using ethyl cellulose (EC), Eudragit RL 100 either solely or in combination by wet granulation technique. Dissolution was carried out in 0.1 N HCl for 2?h followed by pH 6.8 phosphate buffer for eight hours. Uncoated forms released more than 5% drug in 0.1 N HCl therefore, Eudragit L100 was used as a coat. The results indicated very slow release profile. As a result, single retardant was used to prepare the matrix and coated by Eudragit L 100. The matrix containing 7% Eudragit RL 100 and 6% of binder was subjected to further studies to assess the effect of different coats (Eudragit L 100-55 and cellulose acetate phthalate) and different binders (pectin and sodium alginate) on the release profile. Eudragit L 100 and pectin were the best coating agent and binder, respectively. The final formula was stable and it can be concluded that the prepared system has the potential to deliver mebeverine HCl in vivo to the colon.
This deals with fabrication of macromolecular prodrugs (MPDs) of salicylic acid (SA) and aspirin (ASP) based on a hydrophilic cellulose ether, hydroxyethyl cellulose (HEC). Degrees of substitution (DS) of SA and ASP per HEC repeating unit (HEC-RU) were achieved ranging from 0.60 to 2.18 and 0.53 to1.50, respectively. The amphiphilic HEC-SA conjugate 2 assembled into nanowire-like structures, while HEC-ASP conjugate 6 formed nanoparticles (diameter 300-00nm) at a water/DMSO interface. After oral administration in rabbit models, conjugates 2 and 6 showed plasma half-life of 6.96 and 7.01h with maximum plasma concentration (Cmax) of 15.27 and 23.01μg L-1, respectively, and each reached peak plasma concentration (tmax) at 4.0h. Immunomodulatory assays (interleukin 6 and tumor necrosis factor-α values) revealed that anti-inflammatory properties of SA and ASP were unaltered in conjugates. Swelling inhibition of 61 and 71% was observed for conjugates 2 and 6, respectively, in a carrageenan induced paw edema test. Cytotoxic profiling (MTT assay) showed that conjugates were safe for administration in the concentration range of 2-10mM up to 24h. Thermal analyses revealed that Tdm values of SA and ASP conjugates were increased by 99 and 154̊C, respectively, indicating extraordinary thermal stability imparted to drugs after MPD formation.
Cellulose acetate phthalate-based pH-responsive hydrogel was synthesized for fabrication of polymeric matrix tablets for gastro-protective delivery of loxoprofen sodium. Cellulose acetate phthalate (CAP) was cross-linked with methacrylic acid (MAA) using free radical polymerization technique. Fourier transform infrared (FTIR) spectra confirmed the formation of cross-linked structure of CAP-co-poly(methacrylic acid). Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the thermal stability of polymeric networks, and scanning electron microscopy (SEM) and energy-dispersive X-ray spectrum (EDS) images unveiled that the prepared formulations were porous in nature and thus the developed formulations had shown better diffusibility. Swelling and in vitro drug release was performed at various pHs and maximum swelling and release was obtained at pH 7.4, while swelling and release rate was very low at pH 1.2 which confirmed the pH-responsive behavior of CAP-co-poly(MAA). CAP-co-poly(MAA) copolymer prevents the release of loxoprofen sodium into the stomach due to reduced swelling at gastric pH while showing significant swelling and drug release in the colon. Cytotoxicity studies revealed higher biocompatibility of fabricated hydrogel. Acute oral toxicity studies were performed for the evaluation and preliminary screening of safety profile of the developed hydrogels. Matrix tablets were evaluated for release behavior at simulated body pH. The investigations performed for analysis of hydrogels and fabricated matrix tablets indicated the controlled drug release and gastro-protective drug delivery of CAP-co-poly(MAA) hydrogels and pH-sensitive matrix tablets for targeted delivery of gastro-sensitive/irritative agents. Graphical abstract.
The aim of this research is to develop biocompatible nanofibrous mats using hydroxyethyl cellulose with improved cellular adhesion profiles and stability and use these fibrous mats as potential scaffold for skin tissue engineering. Glutaraldehyde was used to treat the scaffolds water insoluble as well as improve their biostability for possible use in biomedical applications. Electrospinning of hydroxyethyl cellulose (5 wt%) with poly(vinyl alcohol) (15 wt%) incorporated with and without collagen was blended at (1:1:1) and (1:1) ratios, respectively, and was evaluated for optimal criteria as tissue engineering scaffolds. The nanofibrous mats were crosslinked and characterized by scanning electron microscope, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Scanning electron microscope images showed that the mean diameters of blend nanofibers were gradually increased after chemically crosslinking with glutaraldehyde. Fourier transform infrared spectroscopy was carried out to understand chemical interactions in the presence of aldehyde groups. Thermal characterization results showed that the stability of hydroxyethyl cellulose/poly(vinyl alcohol) and hydroxyethyl cellulose/poly(vinyl alcohol)/collagen nanofibers was increased with glutaraldehyde treatment. Studies on cell-scaffolds interaction were carried out by culturing human fibroblast (hFOB) cells on the nanofibers by assessing the growth, proliferation, and morphologies of cells. The scanning electron microscope results show that better cell proliferation and attachment appeared on hydroxyethyl cellulose/poly(vinyl alcohol)/collagen substrates after 7 days of culturing, thus, promoting the potential of electrospun scaffolds as a promising candidate for tissue engineering applications.
Acrylated abietic acid (acrylated AbA) and acrylated abietic acid-grafted bacterial cellulose pH sensitive hydrogel (acrylated AbA-g-BC) were prepared by a one-pot synthesis. The successful dimerization of acrylic acid (AA) and abietic acid (AbA) and grafting of the dimer onto bacterial cellulose (BC) was confirmed by 13C solid state NMR as well as FT-IR. X-ray diffraction analysis showed characteristic peaks for AbA and BC; further, there was no effect of increasing amorphous AA content on the overall crystallinity of the hydrogel. Differential scanning calorimetry revealed a glass transition temperature of 80°C. Gel fraction and swelling studies gave insight into the features of the hydrogel, suggesting that it was suitable for future applications such as drug delivery. Scanning electron microscopy observations showed an interesting interpenetrating network within the walls of hydrogel samples with the lowest levels of AA and gamma radiation doses. Cell viability test revealed that the synthesized hydrogel is safe for future use in biomedical applications.
The increase in diseases of the colon underscores the need to develop cost-effective site-directed therapies. We formulated a polysaccharide-based matrix system that could release ibuprofen under conditions simulating those in the colon by employing a wet granulation method. Tablets were prepared in a series of formulations containing a polysaccharide (beta-cyclodextrin and chitosan) matrix system along with ethylcellulose. We characterized physicochemical properties and performed an in vitro drug release assay in the absence and presence of digestive enzymes to assess the ability of the polysaccharides to function as a protective barrier against the upper gastrointestinal environment. Fourier transform infrared spectroscopy studies revealed no chemical interaction between ibuprofen and polysaccharides; however, spectrum analysis suggested the formation of an inclusion complex of beta-cyclodextrin with ibuprofen. The formulations contained 50% ethylcellulose and 50% beta-cyclodextrins (1:1) were proven to be the better formulation that slowly released the drug until 24 h (101.04 ± 0.65% maximum drug release in which 83.08 ± 0.89% drug was released in colonic medium) showed better drug release profiles than the formulations containing chitosan. We conclude that a beta-cyclodextrin drug carrier system may represent an effective approach for treatment of diseases of the colon.
Cellulose acetate phthalate (CAP) microcapsules were formulated to deliver plasmid DNA (pDNA) to the intestines. The microcapsules were characterized and were found to have an average diameter of 44.33 ± 30.22 μm, and were observed to be spherical with smooth surface. The method to extract pDNA from CAP was modified to study the release profile of the pDNA. The encapsulated pDNA was found to be stable. Exposure to the acidic and basic pH conditions, which simulates the pH environment in the stomach and the intestines, showed that the release occurred in a stable manner in the former, whereas it was robust in the latter. The loading capacity and encapsulation efficiency of the microcapsules were low but the CAP recovery yield was high which indicates that the microcapsules were efficiently formed but the loading of pDNA can be improved. In vitro transfection study in 293FT cells showed that there was a significant percentage of green-fluorescent-protein-positive cells as a result of efficient transfection from CAP-encapsulated pDNA. Biodistribution studies in BALB/c mice indicate that DNA was released at the stomach and intestinal regions. CAP microcapsules loaded with pDNA, as described in this study, may be useful for potential gene delivery to the intestines for prophylactic or therapeutic measures for gastrointestinal diseases.
In this study, modified polyethersulfone (PES) and cellulose acetate (CA) membranes were used in the treatment of car wash effluent using ultrafiltration. Hydrophilic sulfonated poly ether ether ketone (SPEEK) and bentonite as nanoclay were used as additives for the PES and CA membrane modification. Performances of modified membranes were compared with commercial PES membrane with 10kDa molecular weight cut off (MWCO). The influencing parameters like stirrer speed (250-750rpm) and transmembrane pressure (100-600kPa) (TMP) were varied and their effects were studied as a function of flux. In the treatment of car wash effluent, a higher permeate flux of 52.3L/m(2)h was obtained for modified CA membrane at TMP of 400kPa and stirrer speed of 750rpm. In comparison with modified PES membrane and commercial PES membrane, modified CA membranes showed better performance in terms of flux and flux recovery ratio. The highest COD removal (60%) was obtained for modified CA membrane and a lowest COD removal (47%) was observed for commercial PES membrane. The modified membranes were better at removing COD, turbidity and maintained more stable flux than commercial PES membrane, suggesting they will provide better economic performance in car wash effluent reclamation.
In this study, a novel fibrous membrane of hydroxyethyl cellulose (HEC)/poly(vinyl alcohol) blend was successfully fabricated by electrospinning technique and characterized. The concentration of HEC (5%) with PVA (15%) was optimized, blended in different ratios (30-50%) and electrospun to get smooth nanofibers. Nanofibrous membranes were made water insoluble by chemically cross-linking by glutaraldehyde and used as scaffolds for the skin tissue engineering. The microstructure, morphology, mechanical and thermal properties of the blended HEC/PVA nanofibrous scaffolds were characterized by scanning electron microscope, Fourier transform infrared spectroscopy, differential scanning colorimetry, universal testing machine and thermogravimetric analysis. Cytotoxicity studies on these nanofibrous scaffolds were carried out using human melanoma cells by the MTT assays. The cells were able to attach and spread in the nanofibrous scaffolds as shown by the SEM images. These preliminary results show that these nanofibrous scaffolds that supports cell adhesion and proliferation is promising for skin tissue engineering.
Cellulose acetate (CA) and cellulose acetate phthalate (CAP) were used as additives (1 wt%, 3 wt%, and 5 wt%) to prepare polyphenylsulfone (PPSU) hollow fiber membranes. Prepared hollow fiber membranes were characterized by surface morphology using scanning electron microscopy (SEM), surface roughness by atomic force microscopy (AFM), the surface charge of the membrane was analyzed by zeta potential measurement, hydrophilicity by contact angle measurement and the functional groups by fourier transform infrared spectroscopy (FTIR). Fouling resistant nature of the prepared hollow fiber membranes was evaluated by bovine serum albumin (BSA) and molecular weight cutoff was investigated using polyethylene glycol (PEG). By total organic carbon (TOC), the percentage rejection of PEG was found to be 14,489 Da. It was found that the hollow fiber membrane prepared by the addition of 5 wt% of CAP in PPSU confirmed increased arsenic removal from water as compared to hollow fiber membrane prepared by 5 wt% of CA in PPSU. The removal percentages of arsenic with CA-5 and CAP-5 hollow fiber membrane was 34% and 41% with arsenic removal permeability was 44.42 L/m2h bar and 40.11 L/m2h bar respectively. The increased pure water permeability for CA-5 and CAP-5 hollow fiber membrane was 61.47 L/m2h bar and 69.60 L/m2 h bar, respectively.
Vitamin D deficiency is now a global health problem; despite several drug delivery systems for carrying vitamin D due to low bioavailability and loss bioactivity. Developing a new drug delivery system to deliver vitamin D3 is a strong incentive in the current study. Hence, an implantable drug delivery system (IDDS) was developed from the electrospun cellulose acetate (CA) and ε-polycaprolactone (PCL) nanofibrous membrane, in which the core of implants consists of vitamin D3-loaded CA nanofiber (CAVD) and enclosed in a thin layer of the PCL membrane (CAVD/PCL). CA nanofibrous mat loaded with vitamin D3 at the concentrations of 6, 12, and 20% (w/w) of vitamin D3 were produced using electrospinning. The smooth and bead-free fibers with diameters ranged from 324 to 428 nm were obtained. The fiber diameters increased with an increase in vitamin D3 content. The controlled drug release profile was observed over 30-days, which fit with the zero-order model (R2 > 0.96) in the first stage. The mechanical properties of IDDS were improved. Young's modulus and tensile strength of CAVD/PCL (dry) were161 ± 14 and 13.07 ± 2.5 MPa, respectively. CA and PCL nanofibers are non-cytotoxic based on the results of the in-vitro cytotoxicity studies. This study can further broaden in-vivo study and provide a reference for developing a new IDDS to carry vitamin D3 in the future.
This study aims to investigate the use of palm olein as the oil phase for betamethasone 17-valerate (BV) emulsions. The physicochemical properties of the formulations were characterized. In vitro drug release study was performed with the Hanson Vertical Diffusion Cell System; the samples were quantified with HPLC and the results were compared with commercial products. Optimized emulsion formulations were subjected to stability studies for 3 months at temperatures of 4, 25, and 40°C; the betamethasone 17-valerate content was analyzed using HPLC. The formulations produced mean particle size of 2-4 μm, viscosities of 50-250 mPa.s, and zeta potential between -45 and -68 mV. The rheological analyses showed that the emulsions exhibited pseudoplastic and viscoelastic behavior. The in vitro release of BV from palm olein emulsion through cellulose acetate was 4.5 times higher than that of commercial products and more BV molecules deposited in rat skin. Less than 4% of the drug was degraded in the formulations during the 3-month period when they were subjected to the three different temperatures. These findings indicate that palm olein-in-water emulsion can be an alternative vehicle for topical drug delivery system with superior permeability.
Cellulose carbamate (CC) was produced from kenaf core pulp (KCP) via a microwave reactor-assisted method. The formation of CC was confirmed by Fourier transform infrared spectroscopy and nitrogen content analysis. The degree of substitution, zeta potential and size distribution of CC were also determined. The CC was characterized with scanning electron microscopy, X-ray diffraction and thermogravimetry analysis. The CC particles were then dispersed in silicone oil to prepare CC-based anhydrous electric stimuli-responsive electrorheological (ER) fluids. Rhelogical measurement was carried out using rotational rheometer with a high voltage generator in both steady and oscillatory shear modes to examine the effect of electric field strength on the ER characteristics. The results showed that the increase in electric field strength has enhanced the ER properties of CC-based ER fluid due to the chain formation induced by electric polarization among the particles.
Polymer electrolytes were developed by solution casting technique utilizing the materials of cellulose acetate (CA), lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and deep eutectic solvent (DES). The DES is synthesized from the mixture of choline chloride and urea of 1:2 ratios. The increasing DES content well plasticizes the CA:LiTFSI:DES matrix and gradually improves the ionic conductivity and chemical integrity. The highest conducting sample was identified for the composition of CA:LiTFSI:DES (28 wt.%:12 wt.%:60 wt.%), which has the greatest ability to retain the room temperature ionic conductivity over the entire 30 days of storage time. The changes in FTIR cage peaks upon varying the DES content in CA:LiTFSI:DES prove the complexation. This complexation results in the collapse of CA matrix crystallinity, observed from the reduced intensity of XRD diffraction peaks. The DES-plasticized sample is found to be more heat-stable compared to pure CA. Nevertheless, the addition of DES diminishes the CA:LiTFSI matrix's heat-resistivity but at the minimum addition the thermal stability is enhanced.
The objective of this research is to investigate the performance of blend cellulose acetate (CA)-polyethersulphone (PES) membranes prepared using microwave heating (MWH) techniques and then compare it with blend CA-PES membranes prepared using conventional heating (CH) methods using bovine serum albumin solution. The superior membranes were then used in the treatment of palm oil mill effluent (POME). Various blends of CA-PES have been blended with PES in the range of 1-5 wt%. This distinctive series of dope formulations of blend CA/PES and pure CA was prepared using N, N-dimethylformamide (DMF) as solvent. The dope solution was prepared by MW heating for 5 min at a high pulse and the membranes were prepared by phase inversion method. The performances of these membranes were evaluated in terms of pure water and permeate flux, percentage removal of total suspended solids (TSS), chemical oxygen demand (COD) and biochemical oxygen demand (BOD). The results indicate that blend membranes prepared using the microwave technique is far more superior compared to that prepared using CH. Blend membranes with 19% CA, 1-3% PES and 80% of DMF solvent were found to be the best membrane formulation.
Conventional fluid-bed and immersion film coating of hydrophilic zinc pectinate pellets by hydrophobic ethylcellulose is met with fast drug release. This study explored in situ intracapsular pellet coating for colon-specific delivery of 5-fluorouracil (5-FU). The solid coating powder constituted ethylcellulose and pectin in weight ratios of 11:0 to 2:9. Its weight ratio to pellets varied between 2:3 and 3:2. Pectin was used as excipient of core pellets and coating powder in view of its potential use in colon cancer treatment. Delayed 5-FU release and core pectin dissolution were attainable when the weight ratio of solid coating powder to pellets was kept at 3:2, and weight ratio of ethylcellulose and pectin in coating powder was kept at 8:3 with particle size of ethylcellulose reduced to 22 μm. In situ intracapsular wetting of pectin coat by dissolution medium resulted in the formation of ethylcellulose plug interconnecting with pellets through the binding action of pectin. Less than 25% of drug was released at the upper gastrointestinal tract. The majority of drug was released upon prolonged dissolution and in response to colonic enzyme pectinase, which digested core pellets.