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Carboxymethylation of Cassia obtusifolia galactomannan was carried out by Williamsons synthesis. Modification of galactomannan was confirmed by Fourier-transform infrared and 1 H-Nuclear magnetic resonance spectroscopy. The degree of carboxymethyl substitution was found to be 1.69. Carboxymethylation was observed to increase the powder flow, solubility and swelling, while decrease the viscosity and alter the compression characteristics from elastic to plastic. The results of X-ray diffraction and scanning electron microscopy studies indicated increase in degree of crystallinity. The modified gum was used for preparing diclofenac sodium-loaded, Ca 2+ -gelled beads which were coated with gastroresistant Eudragit-L100. The formulation of beads was optimized using central composite experimental design. The optimal formulation of beads contained carboxymethylated Cassia galactomannan-2.85%,w/v and calcium chloride -15%,w/v, which showed yield -185.4%, entrapment-95.41% and release of 93.32% of diclofenac over 24 h. The release of diclofenac followed first-order kinetics by Super case-II transport. Thus, carboxymethyl Cassia galactomannan appears suitable for sustained drug delivery., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Natural polymers, particularly polysaccharide, have been used as drug delivery systems for a variety of therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and non-parenteral administration. Chitosan, the second most abundant naturally occurring polysaccharide after cellulose, is a biocompatible and biodegradable mucoadhesive polymer that is extensively used in the preparation of nanoparticles (NPs). Chitosan NPs loaded with drugs were found to be stable, permeable and bioactive. In this review, the importance of chitosan and its derivatives in drug delivery is illustrated, different methods of preparation of chitosan and chitosan derivatives NPs and their physio- chemical properties are addressed. Moreover, the desirable characteristics of successful NPs based drug delivery systems, as well as the pharmaceutical applications of these NPs are also clearly explored., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Polymeric nanoparticles are potential carriers for the efficient delivery of hydrophilic and hydrophobic drugs due to their multifaceted applications. Docetaxel is relatively less hydrophobic and twice as potent as paclitaxel. Like other taxane chemotherapeutic agents, docetaxel is not well tolerated and shows toxicity in the patients. Nanoencapsulation of potent chemotherapeutic agents has been shown to improve tolerability and therapeutic outcome. Therefore, the present study was designed to fabricate chitosan and sodium tripolyphosphate (STPP) based on ionically cross-linked nanoparticles for sustained release of docetaxel., Methods: Nanoparticles were prepared by the ionic-gelation method by dropwise addition of the STPP solution into the chitosan solution in different ratios. CNPs were characterized for post-formulation parameters like size, zeta potential, scanning electron microscope (SEM), FTIR, DSC/TGA, pXRD, and in-vitro drug release, as well as for acute oral toxicity studies in Wistar rats., Results and Discussion: The optimized docetaxel loaded polymeric nanoparticles were in the size range (172.6nm-479.65 nm), and zeta potential (30.45-35.95 mV) required to achieve enhanced permeation and retention effect. In addition, scanning electron microscopy revealed rough and porous surface, whereas, FTIR revealed the compatible polymeric nanoparticles. Likewise, the thermal stability was ensured through DSC and TG analysis, and powder X-ray diffraction analysis exhibited solid-state stability of the docetaxel loaded nanoparticles. The in-vitro drug release evaluation in phosphate buffer saline (pH 7.4) showed sustained release pattern, i.e. 51.57-69.93% within 24 hrs. The data were fitted to different release kinetic models which showed Fickian diffusion as a predominant release mechanism ( R 2 = 0.9734-0.9786, n= 0.264-0.340). Acceptable tolerability was exhibited by acute oral toxicity in rabbits and no abnormality was noted in growth, behavior, blood biochemistry or histology and function of vital organs., Conclusion: Ionically cross-linked chitosan nanoparticles are non-toxic and biocompatible drug delivery systems for sustained release of chemotherapeutic agents, such as docetaxel., Competing Interests: The authors declare no conflicts of interest in this work., (© 2019 Mahmood et al.)

Quercetin (QUE)-loaded nanoparticles (QCG-NPs) were fabricated by ionic gelation between chitosan (CS) and gum arabic (GA) at pH 3.5. At constant CS (0.5 mg/mL) and QUE (60 μM) concentrations, QCG-NPs (260-490 nm) were prepared uniformly with 0.8-2.2 mg/mL GA and exhibited high QUE encapsulation efficiency (94.8-98.0%) and sustained QUE release (4.42-8.89% after 8 h). Because of the electrostatic interaction between QCG-NPs and the mucin layer, in vitro mucin and cell adhesion of QUE were significantly ( p < 0.05) enhanced in QCG-NPs (0.44-0.48 mg/mL and 31.7-78.5%), respectively, and the adhesiveness was significantly ( p < 0.05) increased with an increase of GA. Because particle size and adhesion properties affect the surface area and retention time of QCG-NPs at the absorption site, cell permeation of QUE through simple diffusion by QCG-NPs exhibited the same tendency as the adhesion results. These data were verified in cellular antioxidant and in vivo ferric reducing abilities of plasma assays that evaluated the antioxidant activities of QUE absorbed into an intestinal cell model and rat blood, respectively. The results provide a better understanding of QCG-NP absorption and indicate that QCG-NPs with mucoadhesion properties can be an effective delivery system for improving QUE absorption.

Iron deficiency is the most common nutritional deficit worldwide. The goal of this work was to obtain iron-pectin beads by ionic gelation and evaluate their physiological behavior to support their potential application in the food industry. The beads were firstly analyzed by scanning electronic microscopy, and then physical-chemically characterized by performing swelling, thermogravimetric, porosimetry, Mössbauer spectroscopy and X-ray fluorescence analyses, as well as by determining the particle size. Then, physiological assays were carried out by exposing the beads to simulated gastric and intestinal environments, and determining the iron absorption and transepithelial transport into Caco-2/TC7 cells. Iron-pectin beads were spherical (diameter 1-2 mm), with high density (1.29 g/mL) and porosity (93.28%) at low pressure, indicating their high permeability even when exposed to low pressure. Swelling in simulated intestinal medium (pH 8) was higher than in simulated gastric medium. The source of iron [FeSO 4 (control) or iron-pectin beads] did not have any significant effect on the mineral absorption. Regarding transport, the iron added to the apical pole of Caco-2/TC7 monolayers was recovered in the basal compartment, and this was proportional with the exposure time. After 4 h of incubation, the transport of iron arising from the beads was significantly higher than that of the iron from the control (FeSO 4 ). For this reason, iron-pectin beads appear as an interesting system to overcome the low efficiency of iron transport, being a potential strategy to enrich food products with iron, without altering the sensory properties., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Conventional topical delivery in hyperacute bacterial conjunctivitis and endophthalmitis is associated with low drug bioavailability due to rapid precorneal clearance. Hence, in the present investigation, an attempt has been made to enhance ocular bioavailability of tobramycin sulfate by formulating drug-loaded microparticles dispersed in thermosensitive in situ gel., Methods: Microparticles prepared by emulsion-ionic gelation technique were characterized for drug loading, entrapment efficiency, particle size, surface morphology, and in vitro drug release. Consequently microparticles (F2 prepared with 1.5%w/v chitosan, 0.2%w/v tripolyphosphate, and drug, 30%w/w of polymer) with high drug loading and encapsulation efficiency were dispersed in thermosensitive in situ gel containing poloxamer 407 and varying percentage of chitosan. In situ gel containing drug-loaded microparticles were evaluated for gelation temperature, rheological behavior, mucoadhesive strength, in vitro drug release, in vitro permeation, ocular irritation, and bioavailability in aqueous humor of rabbits., Results: Formulation containing 17%w/v poloxamer 407 and 0.5%w/v chitosan (P2) gelled at 32°C ± 1.5°C gave pseudoplastic behavior. In vitro permeability of tobramycin from the formulation P2 was found 2-folds greater than eye drops. It also gave significantly higher aqueous humor concentration of tobramycin compared with eye drops with no signs of ocular irritation., Conclusion: Thus, the formulation possesses high potential for treating ocular infections.

Aim: The present investigation was aimed to formulate and evaluate Metformin loaded pectin (PCM) nanoparticles (NPs) for sustained action for management of Type 2 Diabetes Mellitus (T2DM)., Method: The nanoparticles were formulated by ionic gelation technique. The nano-formulations were subjected for the analyses of entrapment efficiency and drug release stud for 12h. The optimized formulation examined various in vitro characterizations such as particle size, zeta potential, surface morphology and FTIR studies. The in vitro heamocomptability, protein binding stability and glucose uptake studies were performed with nanoparticles., Results: The PCMNP-4 showed drug entrapment efficiency, 68 ± 4.2 % and demonstrated favourable in vitro prolonged release characteristics. The mean particles diameter of optimized formulation was 482.7 nm and 0.270 poly dispersity index (PI), had spherical shape and zeta potential of (+38.85 mV). In addition, the nanoparticles were reasonably stable in the presence of excess bovine serum albumin, which suggested that the nanoparticles may also be stable in the blood stream. The percentage of haemolysis induced by Metformin and placebo PCNPs were less than 5%. The results indicated that the PCMNPs are hemocompatible and therefore, safe for oral administration. The glucose uptake was increased 1.5 fold in RBCs and L6 skeleton muscle cell line compared with Metformin., Conclusion: Hence, the designed nanoparticle system could possibly be advantageous in terms of prolonged release, to achieve reduced dose frequency and improve patient compliance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Mucoadhesive polymeric films incorporated with ketorolac tromethamine-loaded nanodispersion aiming the sustained delivery of the drug to the cornea have been developed and characterised for the treatment of post-operative ocular inflammation. Nanodispersions were prepared by ionic gelation method with various concentrations of chitosan and sodium tripolyphosphate. The developed nanodispersions were analysed for morphology, particle size, dispersion homogeneity, zeta potential, entrapment efficiency and drug release. The nanodispersion that showed the smallest particle size and the highest entrapment efficiency was incorporated in optimised HPMC E15 and Eudragit RL100/HPMC K4m films. The formulation with optimum physicomechanical properties was selected to study its ex vivo transcorneal permeation through freshly excised bovine cornea in comparison with the nanodispersion and the marketed eye drops (Acular®). The polymeric ocular film showed greater permeation than aqueous eye drops. Moreover, the ocular film revealed a prolonged anti-inflammatory effect compared to eye drops when applied to inflamed rabbit's eyes.

Nanoparticles of two chitosan derivatives - N-succinyl-chitosan (SC) and N-glutaryl-chitosan (GC) - were developed as passive transport systems for taxanes (paclitaxel and docetaxel) using an ionic gelation technique with sodium tripolyphosphate. These nanoparticles had an apparent hydrodynamic diameter of 300-350nm, a ζ-potential of 25-31mV, an encapsulation efficiency of 21-26%, and a drug loading efficiency of 6-13%. DLS and SLS analysis shows that the nanoparticles have a unimodal size distribution and spherical form. Drug release kinetics of the taxane-loaded nanoparticles demonstrates that more than 50% of the loaded taxane could be released upon the degradation of the nanoparticles after targeted delivery. The drug-loaded SC and GC nanoparticles exhibit high cytotoxicity towards AGS cancer cell lines and their antitumor activity is consequently enhanced when compared with free taxanes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Chitosan nanoparticles have been extensively studied for both drug and protein/peptide delivery. The aim of this study was to develop an optimized chitosan nanoparticle, by ionotropic gelation method, using 3 2 full factorial design with a novel polyanion, sodium polyphosphate, well known under the trade name Graham salt. The effects of these parameters on the particle size, zeta potential, and morphology and association efficiency were investigated. The optimized nanoparticles showed an estimated size of 166.20±1.95nm, a zeta potential of 38.7±1.2mV and an efficacy of association of 97.0±2.4%. The Atomic Force Microscopy (AFM) and Scanning Electronic Microscopy (SEM) revealed spherical nanoparticles with uniform size. Molecular interactions among the components of the nanoparticles and peptide were evaluated by Fourier Transform Infrared Spectra (FTIR) and Differential Scanning Calorimetry (DSC). The obtained results indicated that, the developed nanoparticles demonstrated high biocompatible, revealing no or low toxicity in the human cancer cell line (Caco-2). In conclusion, this work provides parameters that contribute to production of chitosan nanoparticles and sodium polyphosphate with desirable size, biocompatible and enabling successful use for protein/peptides delivery., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In recent years, nanoparticles (NPs) based on biopolymers or peptides are gaining popularity for the encapsulation and release of drug molecules, especially for cancer therapy, due to their ability for targeted and controlled release. The use of collagen peptide (CP) for the preparation of chitosan (CN) NPs is especially interesting as it results in NPs that are stable under physiological conditions. In this work, mono-dispersed pH responsive CPCN NPs of about 100nm were prepared via ionic gelation method by simple and mild co-precipitation of CN and CP. Investigation of NPs with Fourier transform infra-red (FTIR) spectroscopy and dynamic light scattering (DLS) measurements reveals that hydrogen bonding and electrostatic interactions are believed to be major driving forces for NP formation and drug encapsulation, respectively. Scanning electron microscopic (SEM) investigations show that hard and fine CPCN NPs transform to soft and bigger gel like particles as a function of collagen concentration. The unique "polymeric gel" structure of NPs showed high encapsulation efficiency towards doxorubicin hydrochloride (DOX) as well as pH controlled release. Anti-proliferative and cell viability analysis revealed that DOX loaded NPs showed excellent anti-proliferative characteristics against HeLa cells with favorable biocompatibility against normal cells. Such NPs have high potential for use as smart drug delivery carriers in advanced cancer therapy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The present study evaluates the in-vitro cisplatin (CDDP) release from four different poly oxalates cross-linked chitosan (CS) nanocomposites. The poly oxalates were synthesized from the reaction of four different dicarboxylic acids with ethylene glycol (EG). The encapsulation of CDDP on CS cross-linked with Oxalic acid-EG, Succinic acid-EG, Citric acid-EG and tartaric acid-EG carriers were carried out by the ionic gelation technique. The poly-oxalate nanocarriers were characterized by scanning electron microscopy, atomic force microscopy, X-ray diffraction studies and zeta potential analysis. The stability of poly-oxalates was calculated by the density functional theory (DFT) using Gaussview 05. Excellent drug release kinetics and good biocompatibility of nanocomposites were observed for the in-vitro analysis. The unloaded poly oxalate nanocomposites perform to have a low inherent cytotoxicity, whereas the loaded nanocomposites were as active as free CDDP in the MCF-7 cancer cell line. The tumor growth inhibitions of CDDP-loaded nanocomposites are more or equal to that of free CDDP. Taken together, these two poly oxalate nanocomposites are established as promising drug carriers for the delivery of CDDP., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: Doxycycline, a broad-spectrum antibiotic, is the most commonly prescribed antibiotic worldwide for treating infectious diseases. It may be delivered orally or intravenously but can lead to gastrointestinal irritation and local inflammation. For treatment of uterine infections, transcervical administration of doxycycline encapsulated in nanoparticles made of biodegradable chitosan may improve sustained delivery of the drug, thereby minimizing adverse effects and improving drug efficacy., Methods and Materials: As a first step toward assessing this potential, we used an ionic gelation method to synthesize blank and doxycycline-loaded chitosan nanoparticles (DCNPs), which we then characterized in terms of several properties relevant to clinical efficacy: particle size, shape, encapsulation efficiency, antibacterial activity, and in vitro cytotoxicity. Two particle formulations were examined, with one (named DCNP6) containing approximately 1.5 times the crosslinker concentration of the other (DCNP4)., Results: The two formulations produced spherically shaped drug-loaded nanoparticles. The spheres ranged in size from 30 to 220 nm diameter for DCNP4 and 200 to 320 nm diameter for DCNP6. Average encapsulation yield was 53% for DCNP4 and 56% for DCNP6. In terms of drug release, both formulations showed a burst effect within the first 4 to 5 hours, followed by a slow, sustained release for the remainder of the 24-hour monitoring period. The in vitro antibacterial activity against Escherichia coli was high, with both formulations achieving more than 90% inhibition of 4-hour bacterial growth. Cytotoxic effects of the DCNPs on normal human ovarian surface epithelial cells were significantly lower than those of unencapsulated doxycycline. After 5 days, cultures exposed to the unencapsulated antibiotic showed a 61% decrease in cell viability, while cultures exposed to the DCNPs exhibited less than a 10% decrease., Conclusion: These laboratory results suggest that DCNPs show preliminary promise for possible eventual use in transcervical drug delivery and improved efficacy in the treatment of bacterial uterine infections.

A common challenge in hydrogel-based delivery systems is the premature release of low molecular weight encapsulates through diffusion or swelling and reduced cell viability caused by the low pH in gastric conditions. A second biopolymer, such as chitosan, can be incorporated to overcome this. Chitosan is usually associated with colonic drug delivery systems. We intended to formulate chitosan-coated pectin beads for use in delaying premature release of the encapsulate under gastric conditions but allowing release through disintegration under intestinal conditions. The latter is of utmost importance in delivering most functional food ingredients. Therefore, this study investigated the impact of formulation and process conditions on the size, sphericity, and dissolution behavior of chitosan-coated hydrogel beads prepared by interfacial coacervation. The size and sphericity of the beads depend on the formulation and range from approximately 3 to 5 mm and 0.82 to 0.95, respectively. Process conditions during electro-dripping may be modulated to tailor bead size. Depending on the voltage, bead size ranged from 1.5 to 4 mm. Confocal laser scanning microscopy and scanning electron microscopy confirmed chitosan shell formation around the pectin bead. Chitosan-coated beads maintained their size and shape in simulated gastric fluid but experienced structural damage in simulated intestinal fluid. Therefore, they represent a novel delivery system for functional food ingredients. [ABSTRACT FROM AUTHOR]

In this study, we fabricated and characterized nanometric chitosan (Cs)/laponite (La) nanocomposite nanogels for controlled drug delivery applications. Cs and Cs/La nanocomposite nanogels were formed by ionic gelation method using tripolyphosphate. The release of honey as a model drug was monitored using a blood glucose meter. The results of dynamic light scattering and field emission scanning electron microscopy demonstrated that in the wet state, the mean particle size of nanogels were 133 nm and 118 nm for Cs nanogels and Cs/La nanocomposite nanogels, moderately reducing to 32 nm and 95 nm at dried state, respectively. X-ray diffraction analysis confirmed exfoliated morphology for nanocomposite nanogels. Although honey loading increased the size of the nanogels, it had no effect on the morphology of nanocomposite nanogels. The loading efficiency and loading capacity of encapsulation decreased in nanocomposite nanogels. The honey release profile of nanocomposite nanogels began with a burst release, and showed lower values compared to Cs nanogels during the first hour. Our results corroborated to the higher cross-linking density and barrier effect of La in nanocomposite nanogels. [ABSTRACT FROM AUTHOR]

Objectives: In the present investigation a novel oral drug delivery system was developed by combining two different techniques floating and mucoadhesive system so called floatadhesive, in order to obtain a controlled system that could remain in the stomach for prolonged period and release the drug in a controlled manner. Materials and Methods: Microspheres containing Famotidine were prepared by ionic gelation method using Mimosa pudica seed mucilage as a natural mucoadhesive polymer. Sodium alginate (SA) and chitosan (CS) were incorporated as drug release modifier. The microspheres were characterized by scanning electron microscopy and evaluated by employing shape and particle size, % drug entrapment efficiency, in vitro floating ability, in vitro mucoadhesion and in vitro drug release pattern. Results: The prepared microspheres were acceptably spherical with a mean particle size in the range of 334 ± 1.18 µm to 498 ± 1.12 µm. Drug entrapment efficiency was observed in the range of 72.82 ± 1.10% to 92.38 ± 1.20%. Formulations containing a combination of both mucilage and chitosan showed increased in vitro mucoadhesion and buoyancy as compared to formulations containing chitosan alone. In vitro drug release for all the formulations in 0.1N HCl was diffusion controlled gradually throughout 12 h and followed Higuchi's and Korsmeyer Peppas kinetics. The mechanism of in vitro drug release was non-fickian type controlled by swelling and relaxation of the polymer. Conclusion: The developed microspheres have dual advantages of being floating and mucoadhesive to increase oral bioavailability and releasing drug in a controlled manner, to reduce the required frequency of administration thereby promoting patient compliance. [ABSTRACT FROM AUTHOR]

Chitosan, as a natural polysaccharide, has a unique structure and multi-functional properties. One of the most prominent specifications of chitosan is high biocompatibility, good biodegradability, low toxicity and antibacterial and antiallergenicity properties. Chitosan has a high potential for controlled drug delivery. Therefore, investigating the loading capacity and release rate of chitosan at different conditions is important. By reducing particle size, chitosan has shown a high ability of teicoplanin loading due to its cationic property, which is important in this research. The aim of this study was to investigate chitosan nanoparticle potential for use in biomedical devices for drug delivery systems. Nanoparticles were prepared by ionic gelation with tripolyphosphate (TPP) ion, and the factors that affected chitosan nanoparticle size were investigated. The prepared samples were characterized using DLS, FTIR, TGA, DSC and XRD techniques. It is found at best condition with CS/TPP ratio of 2:1 nanoparticles were obtained at an average size of about 100 nm. The results confirmed that the drug (teicoplanin) loaded on the TPP cross-linked chitosan nanoparticles causes an increase in nanochitosan size and there was no interaction between teicoplanin and chitosan. Also, it is observed that 28.2% of teicoplanin was released in the first 10 h and the release is continued gradually to receive 37.4% in 100 h. Thus, it seems that chitosan nanoparticles mitigate the drug release and are suitable for sustained drug release. [ABSTRACT FROM AUTHOR]

Drug delivery to lungs via pulmonary administration offers potential for the development of new drug delivery systems. Here we fabricated the etofylline (ETO) encapsulated mannose-anchored N , N , N -trimethyl chitosan nanoparticles (Mn-TMC NPs). The prominent characteristics like biocompatibility, controlled release, targeted delivery, high penetrability, enhanced physical stability, and scalability mark Mn-TMC NPs as a viable alternative to various nanoplatform technologies for effective drug delivery. Mannosylation of TMC NPs leads to the evolution of new drug delivery vehicle with gratifying characteristics, and potential benefits in efficient drug therapy. It is widely accepted that following pulmonary administration, the introduction of mannose to the surface of drug nanocarriers provide selective macrophage targeting via receptor-mediated endocytosis. The fabricated Mn-TMC NPs exhibited particle size of 223.3 nm, PDI 0.490, and ζ-potential −19.1 mV, drug-loading capacity 76.26 ± 1.2%, and encapsulation efficiency of 91.75 ± 0.88%. Sustained drug release, biodegradation studies, stability, safety, and aerodynamic behavior revealed the effectiveness of prepared nanoformulation for pulmonary administration. In addition, the in vivo pharmacokinetic studies in Wistar rat model revealed a significant improvement in therapeutic efficacy of ETO, illustrating mannosylation a promising approach for efficient therapy of airway diseases following pulmonary administration. Unlabelled Image • The N , N , N -trimethyl chitosan chloride is synthesized and subsequently mannosylated. • The nanoparticles are prepared using sodium tripolyphosphate by ionotropic gelation mechanism. • Etofylline is successfully loaded into TMC-TPP and MnTMC-TPP NPs. • The prepared nanoparticle formulations are efficient in delivering etofylline to lungs. • The in vivo pharmacokinetics revealed enhanced therapeutic efficacy following pulmonary delivery. [ABSTRACT FROM AUTHOR]

The current research was planned to enhance the bioavailability of hydrophobic drug after oral administration through the development of a nanoparticle drug delivery system (DDS). Therefore, febuxostat-loaded chitosan nanoparticles (FLC NPs) were prepared using a modified ionic gelation method and optimized the reaction conditions through the design of experiments. Design expert software was used to check the desirability of the central composite design and the interactive effects of the independent variables (chitosan concentration, ratio of chitosan to linker, and pH of the medium) on the response variables (size distribution, zeta potential, polydispersity index (PDI), and entrapment efficiency (EE)) of FLC NPs. All ingredients of the optimized formulation (formulation Q) were compatible with each other as evident from FTIR, PXRD, and TGA studies, and displayed 234.7 nm particle size, 0.158 PDI, 25.8 mV zeta potential, and 76.9 % EE. TEM, SEM, and AFM exhibited a smooth, dense, and uniform structure without any visible pores in the structure of FLC NPs. The in vitro and in vivo drug release studies described a sustained release pattern of febuxostat and increased relative bioavailability by 286.63 %. Considering these findings, this chitosan nanoparticle DDS can further be used for improving the EE and bioavailability of hydrophobic drugs. [ABSTRACT FROM AUTHOR]

Purpose: To prepare and characterise doxorubicin nanopatrticles and study their drug delivery in breast cancer. Methods: Doxorubicin nanoparticles were prepared by ionic gelation method using sodium alginate as polymer. The formulations were optimized by cross-linking CaCl2 with sodium alginate at different concentrations. Zeta sizer Nano ZS (UK) was used to determine the mean particle size distribution of the nanoparticle preparations. The shape and external morphologies of the nanoparticles were evaluated by scanning electron microscopy (SEM). Drug release was determined and kinetic release analysis was applied to determine the mechanism of drug release. Results: Entrapment efficiency and mean particle size values were correlated. Scanning electron micrographs showed that the nanoparticles were spherical with little irregularity but without cracks. Doxorubicin release from the sodium alginate nanoparticles followed Korsmeyer-Peppas model which suggest that drug release from the nanoparticles was by diffusion and dissociation from the natural polymer matrix. Conclusion: The doxorubicin-loaded nanoparticles showed concentration-dependent increases in entrapment efficiency. The nanoparticles displayed anticancer properties in breast cancer cell line, thus indicating its potential fo chemotherapeutic application. [ABSTRACT FROM AUTHOR]

The objective of this study is to demonstrate an effective technique with potential for commercialization for microsphere production. Ultrasound-assisted ionic gelation of sodium alginate was used to encapsulate simvastatin. Chitosan was used as a mucoadhesive polymer for gastroretention of microsphere. Sodium alginate solution was sonicated using probe sonicator at a frequency of 20±3 KHz and ultrasonic power of 130 W with an input voltage range of 170-270 AC, 50 Hz, at a temperature of 50°. The influence of ultrasound waves on drug entrapment efficiency, yield and particle size dispersion was studied in comparison to mechanical stirring method. Mucoadhesiveness, release pattern and kinetics of drug release were also characterized. Ultrasound treatment caused small fissures and depressions on the surface of alginate as evidenced in SEM. Ultrasound of 20±3 KHz for 12 min duration was the optimum frequency and time in the experimental set up to obtain microspheres with uniform and smaller microparticles. The encapsulation efficiency of simvastatin was directly proportional to the sonication effect, concentration of alginate and extent of its cross linkage with calcium ions. DSC studies revealed that ultrasound treatment did not alter the structural integrity of the drug component. Formulation was found to be dissolution efficient and drug release pattern was concentration-dependent, which followed non-Fickian diffusion mechanism with an 'n' value of 0.8. Therefore, it could be concluded that ultrasound can be used as an efficient technology to develop drug-entrapped microsphere for controlled delivery. [ABSTRACT FROM AUTHOR]

The current study is aimed at developing Plantago ovata F. husk mucilage (PHM)-blended Zn2+-crosslinked low methoxyl (LM) pectinate (PHM-Zn2+- LM-pectinate) controlled-release matrices containing aceclofenac (ACF) for the management of rheumatoid arthritis (RA) in patients with an outright zinc deficiency. The ACF-encapsulated hydrogel matrices are accomplished by ionic gelation using ZnSO4 as a crosslinker. The matrix diameter ranges from 1.39±0.14 to 1.62±0.16 mm. These formulations demonstrate excellent drug encapsulation efficiency (DEE, 63.80±1.73-90.56±2.72%) and controlled drug-release behavior over a prolonged period of time (Q10 h, 51.42±3.10 to 92.60±2.38%). The drug-elution patterns of different matrices are best-fitted by a zero-order kinetic model with a case-II-transportdriven mechanism. The matrices also depict pH-dependent swelling and degradation properties. In addition, the composites are characterized by scanning electron microscopy (SEM), Fourier transform IR (FTIR), and powder X-ray diffraction (P-XRD) analyses. Thus, the newly developed PHM-Zn+2-LM-pectinate matrices could be appropriate for controlled ACF delivery along with Zn supplementation in the effective treatment of RA. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 2 (FGF-2) is a multi-functional protein involving in wound healing. However, FGF-2 is easily degradable in vivo , which limited its use for wound treatment. In this study, we investigated a drug-delivery model for FGF-2 via incorporation with biodegradable carboxylmethyl chitosan (CMCS). CMCS nanoparticles (NPs) could be synthesized by ionic gelation using CaCl 2 as a crosslinking reagent with the CMCS:CaCl 2 ratio of 1:0.8. Synthesized CMCS NPs had a diameter of 32.68 ± 6.83 nm, and were non-toxic at concentrations up to 2.5 mg/ml. Incorporated CMCS:FGF‐2 NPs had a diameter of 34.83 ± 5.89 nm and incorporation efficiency was 95%. CMCS:FGF‐2 NPs released 36.36% and 58.47% of FGF‐2 after 48 h incubation in two different pH of 7.4 and 5.8, respectively. The incorporation and release processes did not have a significant effect on FGF-2 activity. Simultaneously, CMCS:FGF-2 NPs could protect FGF‐2 from the degradation of trypsin in vitro . Our results laid the groundwork for the manufacturing of protein incorporated CMCS NPs for bio‐applications. [ABSTRACT FROM AUTHOR]

Background: There has been increased attention given to polymeric nanoparticles as protein carriers. In this regard, chitosan/tripolyphosphate (TPP) nanoparticles are considered to be a simple and efficient carrier. However, to have an ideal protein release profile, we need to optimize the properties of the carrier. Methods: This study examined the influence of 4 critical process parameters on the physicochemical characteristics of final nanoparticles. Chitosan-based nanoparticles were produced by ionic gelation, and then the size, polydispersity and zeta potential of those resulting nanoparticles were evaluated. Subsequently, the encapsulation efficiency of bovine serum albumin as model protein was investigated. Results: The morphologies of nanoparticles were characterized using field emission scanning electron microscopy (FE-SEM). Linear mathematical models were presented for each response through 3 levels using Central Composite Design with the help of design of experiments software, and formulation optimization was performed. Conclusions: Such research will serve as a basic study in protein loading into TPP cross-linked chitosan nanoparticles. [ABSTRACT FROM AUTHOR]

Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using sulfo-SMCC as a bifunctional linker to afford COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR, 1 H NMR, 13 C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1 mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of a cell-impermeable cargo ( e.g. , F′-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian carcinoma (SK-OV-3) cancer cell lines. Additionally, RGD modified and unmodified COS polymers were used to prepare nanoparticles by ionic gelation and showed particle size ranging from 187 to 338 nm, and zeta potential of 12.2–18.3 mV using dynamic light scattering. The efficiency of COS-NPs and COS-SMCC-RGDSK NPs was assayed for translocation of two synthetic cytotoxic agents ((2-(2-aminoethylamino)-4-(4-chlorophenyl)-6-(1H-indol-3-yl) nicotinonitrile (ACIN), and 2-(2-aminoethylamino)-6-(1H-indol-3-yl)-4-(4-methoxyphenyl)-nicotinonitrile (AMIN)) into CCRF-CEM and human prostate (DU-145) cancer cell lines. The results showed a dramatic reduction in the cell viability on their treatment with RGD targeted COS NPs in comparison to paclitaxel (PTX), free drug, and drug-loaded COS NPs. [ABSTRACT FROM AUTHOR]

The chemical potentials of drug–polymer electrostatic interaction have been utilized to develop a novel ternary chitosan–ibuprofen–gellan nanogel as controlled transdermal delivery tool for ibuprofen. The ternary nanogels were prepared by a combination of electrostatic nanoassembly and ionic gelation techniques. The electrostatic and hydrophobic interactions as well as hydrogen bonding between ibuprofen and chitosan were confirmed with FTIR, while DSC, TGA and SEM confirmed the physical state, thermal and morphological characteristics, respectively. The ex vivo delivery of ibuprofen onto and across the skin was evaluated based on system specific drug release parameters such as steady state permeation rate, permeability coefficient, permeability enhancement ratio, skin/gel partition coefficient, diffusion coefficient, lag time and release rate constant and mechanisms of release were determined using mathematical models. Interaction between ibuprofen and chitosan produced new spherical eutectic nanoconjugates with remarkable decrease in particle size of ibuprofen from 4580 (length-to-breadth aspect ratio) to a minimum of 14.15 nm (324-times), and thermally stable amorphous characteristics. The nanogels exhibited significant elastic and pseudoplastic characteristics dictated by the concentration of chitosan with maximum swelling capacity of 775% w/w at 6.55 mM chitosan compared with 281.16 and 506.50% for plain gellan and control ibuprofen hydrogel, respectively. Chitosan enhanced the skin penetration, permeability and the rate of transdermal release of ibuprofen by a factor of 4, dictated by the extent of ibuprofen–chitosan ionic interaction and its concentration. The major mechanism of ibuprofen release through the pig skin was drug diffusion however drug partition and matrix erosion also occurred. It was evident that ternary nanogels are novel formulations with potential application in controlled transdermal delivery of ibuprofen. [ABSTRACT FROM AUTHOR]

Naringenin (NAR), a natural flavonoid aglycone of naringin has been extensively investigated for its pharmacological activities, including anti-tumor effects. However, its poor bioavailability has been identified as the single most important challenge in oral drug delivery. Based in this condition, it is used nanoencapsulation to increase the effectiveness of NAR as anticancer. The objectives of this research were to develop the formulation of NAR-loaded nanoparticles (NARNPs) as well as to evaluate its potential as anti-cancer against T47D breast cancer cells line. NARNPs is prepared through the method of ionic gelation, meanwhile its characteristic is evaluated through photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), fourier transform infra-red spectroscopy (FTIR), and different scanning calorimeter (DSC). The result of MTT test and cellular uptake indicate that NARNPs increase cytotoxicity and internalization of NAR to the cells compared to that of free NAR. The result of qualitative apoptosis study using fluorescence microscope indicates that both free NAR and NARNPs were able to induce apoptosis. It can be conclude that Chitosan nanoparticles- TPP conjugates have the capability to encapsulate naringenin hence increase the cellular uptake and cytotoxcicity of naringenin against T47D cell line. NARNPs also could induce the apoptosis effect. [ABSTRACT FROM AUTHOR]

Chitosan-tripolyphosphate (TPP) nanoparticles have received great interest as a drug delivery system due to the simple and mild procedure of ionic gelation and the biocompatibility of chitosan. We have studied the formation of chitosan nano- and microparticles through ionic gelation with TPP in the absence and presence of NaCl, by measuring the kinetics of formation, particle size, and zeta potential. Depending on the experimental conditions (concentrations of chitosan and TPP and the presence or absence of NaCl), particle formation displays an exponential or a sigmoidal time dependency. In order to explain the kinetics measurements, we have set up a simple kinetics model involving four different species. The model is constructed on the basis of previously proposed mechanisms of particle formation and our measurements of particle size and kinetics of formation. The model can simulate all the different time dependencies of particle formation. We also determined the effect of small interfering RNA (siRNA) on the rate of particle formation, but apparently siRNA has little or no influence on particle formation when TPP is present. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study is to synthesize chitosan (CS) nanoparticles (NPs) by ionic gelation with tripolyphosphate (TPP) as crossslinker in static mixers. The proposed static mixing technique showed good control over the ionic gelation process and 152–376nm CS NPs were achieved in a continuous and scalable mode. Increasing the flow rates of CS:TPP solution streams, decreasing the CS concentration or reducing the CS:TPP solution volume ratio led to the smaller particles. Sylicylic acid (SA) was used as a model drug and successfully loaded into the CS NPs during the fabrication process. Our work demonstrates that ionic gelation–static mixing is a robust platform for continuous and large scale production of CS NPs for drug delivery. [Copyright &y& Elsevier]

Abstract: Chitosan (CS) grafted with β-cyclodextrin (CD-g-CS) nanoparticles as a new carrier for poorly water-soluble drugs has been developed. The CD-g-CS polymer is readily synthesized from chitosan and mono-6-deoxy-6-(p-toluenesulfonyl)-β-cyclodextrin. Three different degrees of substitution (DS) of β-cyclodextrin (β-CD) on CD-g-CS (9.6, 14.0 and 20.0%) are designed and evaluated by controlling the mole ratio of β-CD to chitosan. Then CD-g-CS nanoparticles are prepared by an ionic gelation method, with the controlled size of 202.0–589.0nm. Stable colloidal dispersion of the nanoparticles has been formed with the zeta potential of +23.0 to +43.0mV. In vitro stability test indicates that CD-g-CS nanoparticles are more stable in phosphate-buffered saline compared with CS nanoparticles. Finally, the poorly water-soluble drug, ketoprofen (KTP), is used as a model drug to evaluate the efficiency of the new drug delivery carrier. It is found that the encapsulation efficiency of KTP in the nanoparticles with 20% DS of CD is as high as 1.36-fold than that of CS nanoparticles. Moreover, notably KTP is released from the nanoparticles in a controlled-release manner and is pH-responsive on DS of CD. In summary, these results suggest that the CD-g-CS nanoparticles, as a general promising drug delivery system, can be used as a potential biodegradable nano-drug delivery system for controlled release of poorly water-soluble drugs with pH-responsive capability. [Copyright &y& Elsevier]

Abstract: The aim of current study was to illustrate a strategy to encapsulate itraconazole into chitosan-based nanoparticles using a modified ionic gelation method and to fabricate them as inhalable microparticles using spray drying technique. Different ratios of chitosan:tripolyphosphate (TPP) were prepared at pH 1.2, using higher ratios of TPP with respect to chitosan. The highest encapsulation efficiency of itraconazole into chitosan nanoparticles was found to be about 55% at 1:3 ratio of chitosan:TPP. Increasing the amount of TPP 4 times higher than chitosan resulted in the production of large particles in micron scale. Below the ratio of 1:3, the particle sizes ranged from 190 to 240nm. Nanoparticles were characterized for morphology by TEM images. Microparticles were prepared by co-spray drying of nanoparticles with 2.5, 10 and 20% of lactose and mannitol with or without 10% of leucine, with respect to nanoparticle weights. In vitro inhalation parameters including fine particle fraction (FPF) and emitted dose percentage (ED%) were measured by a twin stage impinger (TSI). The in vitro deposition data indicated that processing of nanoparticles with mannitol and leucine could improve the aerosolization properties of the drug significantly. [Copyright &y& Elsevier]

Abstract: Chitosan is one of the most promising polymers for drug delivery through the mucosal routes because of its polycationic, biocompatible, and biodegradable nature, and particularly due to its mucoadhesive and permeation-enhancing properties. Bile salts are known to interact with lipid membranes, increasing their permeability. The addition of bile salts to chitosan matrices may improve the delivery characteristics of the system, making it suitable for mucosal administration of bioactive substances. In the present study we have developed chitosan nanoparticles using sodium deoxycholate as a counter ion and evaluated their potential as gene delivery carriers. Chitosan–sodium deoxycholate nanoparticles (CS/DS) obtained via a mild ionic gelation procedure using different weight ratios were used to encapsulate plasmid DNA (pDNA) expressing a “humanized” secreted Gaussia Luciferase as reporter gene (pGLuc, 5.7kDa). Mean particle size, polydispersity index and zeta potential were evaluated in order to select the best formulation for further in vitro studies. The nanoparticles presented an average size of 153–403nm and a positive zeta potential ranging from +33.0 to +56.9mV, for nanoparticles produced with CS/DS ratios from 1:4 to 1:0.6 (w:w), respectively. The pDNA was efficiently encapsulated and AFM studies showed that pDNA-loaded nanoparticles presented a more irregular surface due to the interaction between cationic chitosan and negatively charged pDNA which results in a more compact structure when compared to empty nanoparticles. Transfection efficiency of CS/DS–pDNA nanoparticles into moderately (AGS) and well differentiated (N87) gastric adenocarcinoma cell lines was determined by measuring the expression of luciferase, while cell viability was assessed using the MTT reduction. The CS/DS nanoparticles containing encapsulated pDNA were able to transfect both AGS and N87 cell lines, being more effective with AGS cells, the less differentiated cell line. The highest enzymatic activity was achieved with 20% pDNA encapsulated and after 24h of transfection time. Low cytotoxicity was observed for the CS/DS nanoparticles either with or without pDNA, suggesting this could be a new potential vehicle for mucosal delivery of pDNA. [Copyright &y& Elsevier]

In this study, tamoxifen citrate-loaded chitosan nanoparticles (tamoxcL-ChtNPs) and tamoxifen citrate-free chitosan nanoparticles (tamoxcF-ChtNPs) were prepared by an ionic gelation (IG) method. The physicochemical properties of the nanoparticles were analyzed for particle size, zeta (ζ) potential, and other characteristics using photon correlation spectroscopy (PCS), zeta phase analysis light scattering (PALS), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and differential scanning calorimetry (DSC). The variation in particle size was assessed by changing the concentration of chitosan, pentasodium tripolyphosphate (TPP), and the pH of the solution. The optimized tamoxcL-ChtNPs showed mean diameter of 187 nm, polydispersity of 0.125, and ζ-potential of +19.1 mV. The encapsulation efficiency (EE) of tamoxifen citrate (tamoxc) increased at higher concentrations, and release of tamoxc from the chitosan matrix displayed controlled biphasic behavior. Those tamoxcL-ChtNPs tested for chemosensitivity showed dose- and time-dependent antiproliferative activity of tamoxc. Further, tamoxcL-ChtNPs were found to be hemocompatible with human red blood cells (RBCs) and safe by in vitro cytotoxicity tests, suggesting that they offer promise as drug delivery systems in therapy. [ABSTRACT FROM AUTHOR]

The study was focused on synthesis and characterization of new core-shell drug delivery systems, based on natural polymers, encapsulating tuberculostatic agents. There have been prepared microcapsules based on chitosan and gelatin using an emulsion-crosslinking technique. The microcapsules were characterized by determining their morphology, size, size distribution and swelling degree in aqueous media. The toxicity and biological activity of the loaded microcapsules were determined. [ABSTRACT FROM AUTHOR]

In this study the preparation and stabilization of poly(acrylic acid)-cysteine nanoparticles and incorporation of a fluorescence marked model-compound was investigated. Nanoparticles were prepared by ionic gelation of a poly(acrylic acid)-cysteine conjugate with calcium chloride. Poly(acrylic acid)-cysteine nanoparticles display high cohesive properties due to a cross-linking process via calcium bridges in the core and the pervasive formation of disulphide bonds and were 139 ± 34 nm in size. Nanoparticles were loaded with FITC-dextrans (flourescein isothiocyanate-dextrans) of 4, 20 and 40 kDa molecular mass as model-compound via sonication method or via vibration method for 3 and 24 h. In vitro release studies showed an initial burst release followed by an extended release of model-compounds. The lower the molecular mass of the FITC-dextrans, the higher was the amount of incorporated and released model compounds. Vibration seems to be a proper method for the incorporation of hydrophilic and macromolecular drugs in poly(acrylic acid)-cysteine nanoparticles. [ABSTRACT FROM AUTHOR]

Cyclosporine A (CsA) is a potent immunosuppressant for treating ulcerative colitis (UC). However, owing to severe systemic side effects, CsA application in UC therapy remains limited. Herein, a colon-targeted drug delivery system consisting of CsA crystals (CsAc)-loaded, Eudragit S 100 (ES)-coated alginate microparticles (CsAc-EAMPs) was established to minimize systemic side effects and enhance the therapeutic efficacy of CsA. Homogeneously-sized CsAs (3.1 ± 0.9 μm) were prepared by anti-solvent precipitation, followed by the fabrication of 47.1 ± 6.5 μm-sized CsAc-EAMPs via ionic gelation and ES coating. CsAc-EAMPs exhibited a high drug loading capacity (48 ± 5%) and a CsA encapsulation efficacy of 77 ± 9%. The in vitro drug release study revealed that CsA release from CsAc-EAMPs was suppressed under conditions simulating the stomach and small intestine, resulting in minimized systemic absorption and side effects. Following exposure to the simulated colon conditions, along with ES dissolution and disintegration of alginate microparticles, CsA was released from CsAc-EAMPs, exhibiting a sustained-release profile for up to 24 h after administration. Given the effective colonic delivery of CsA molecules, CsAc-EAMPs conferred enhanced anti-inflammatory activity in mouse model of dextran sulfate sodium (DSS)-induced colitis. These findings suggest that CsAc-EAMPs is a promising drug delivery system for treating UC. [ABSTRACT FROM AUTHOR]

Abstract: In the past decade, many strategies have been developed to enhance oral protein delivery. The aim of the current work was to develop a nanoparticulate system based on ionic gelation between chitosan and Arabic gum for loading of insulin. Various formulations were prepared using 23 factorial designs. The optimum association efficiency was obtained for formulations F2, F5, and F8. The release profile of insulin in phosphate buffer solutions (pH 6.5 and pH 7.2) is completely different than that in acidic medium (pH 1.2). Increased solubility of chitosan in acidic medium and better swelling of Arabic gum chains at pH >6.5 resulted in lower insulin release of nanoparticles at pH 6.5 in comparison with that of the other pH mediums. The values of the exponent n were 0.49 and 0.82 for formulations F8 and F5, respectively, indicating a non-Fickian transport. This suggests that release is possibly controlled by diffusion or relaxation of the polymer chains. From the Clinical Editor : This paper summarizes the development of a nanoparticulate system based on ionic gelation between chitosan and gum Arabic for oral delivery of insulin. If preclinical studies in animal models will indicate reliable and quantifiable delivery of insulin, this method may pave the way to a novel and less invasive way of administering insulin to diabetes patients. [Copyright &y& Elsevier]