Analytical characterization of chitosan nanoparticles for peptide drug delivery applications

Chitosan-cyclodextrin hybrid nanoparticles (NPs) were obtained by the ionic gelation process in the presence of glutathione (GSH), chosen as a model drug. NPs were characterized by means of transmission electron microscopy and zeta-potential measurements. Furthermore, a detailed X-ray photoelectron spectroscopy study was carried out in both conventional and depth-profile modes. The combination of controlled ion-erosion experiments and a scrupulous curve-fitting approach allowed for the first time the quantitative study of the GSH in-depth distribution in the NPs. NPs were proven to efficiently encapsulate GSH in their inner cores, thus showing promising perspectives as drug carriers.     

Characterization and biodegradation of chitosan-alginate polyelectrolyte complexes

Polyelectrolyte complexes (PECs) have been the focus of an expanding number of studies for their wide use. This study investigated the characteristics and biodegradation of chitosan-alginate PECs prepared by freeze-drying a precipitate from sufficient mixtures of the two polymers. The analyses of X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) suggested that the partial protonated amine groups of chitosan reacted with the carboxylate groups of alginate and thus strong PECs were formed. After incubating in lysozyme solution, the PECs showed high ability of enzyme adsorption, and low degradation rate in spite of different degrees of deacetylation of chitosan, due to the strong interaction between chitosan and alginate and the hindrance of closely adsorbed lysozyme.     

Synthesis and characterization of a pH responsive and mucoadhesive drug delivery system for the controlled release application of anti-cancerous drug

In this work a novel pH sensitive composite, polyacrylamide grafted succinyl chitosan intercalated bentonite (AAm-g-NB/SC) was prepared as a drug carrier system for the controlled delivery of paclitaxel. Characterization of the drug delivery system was carried out using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal analysis etc. The equilibrium swelling behaviour of the composite was studied and the result showed a maximum at pH 7.4. The in vitro drug release study of paclitaxel indicated that about 15.6% of drug release was found to be occurred at pH 1.2 within 16 h, whereas about 82.5% of drug release was occurred at the intestinal pH condition of 7.4. In vitro biocompatibility study was performed and the result showed good biocompatibility of the composite in the concentration range 6.25–100 µg/mL. The cytotoxicity assay was carried out in cancerous cell line of Human colorectal Adenocarcinoma. Mucous glycoprotein assay study showed that the drug delivery system having good apparent adhering property towards mucin. The investigation indicated that paclitaxel, an anticancer drug can be successfully entrapped in the AAm-g-NB/SC composite for the controlled and targeted delivery for colorectal cancer therapy.     

Preparation and characterization of metronidazole‐loaded chitosan nanoparticles for drug delivery application

This study describes the preparation of mucoadhesive chitosan nanoparticles containing metronidazole (MZ) intended for colon‐specific delivery. The chitosan nanoparticles were prepared by the ionic gelation method and their in vitro properties were studied. The release profiles of MZ from the nanoparticles were determined by UV–Vis absorption measurement at λ_max 278 nm. Scanning electron microscopy was used for morphology observation. The nanoparticles exhibited mucoadhesive properties, which diminished with increasing drug content. The nanoparticles with a particle size range between 200 and 300 nm exhibited excellent mucoadhesive properties. The results show that the formulated nanoparticles have succeeded in controlling the release of MZ over a 12‐hr period. In conclusion, the release of MZ was found to be dependent upon the composition of the nanoparticles, the ratio of the components and possible particle size, as well as bioadhesive ability. Copyright © 2008 John Wiley & Sons, Ltd.     

Construction of a pH-responsive drug delivery platform based on the hybrid of mesoporous silica and chitosan

Mesoporous silica nanoparticles (MSN) have been widely used for drug delivery due to their large specific surface area and excellent biocompatibility. However, the mesoporous structure of MSN would lead to the inevitable “premature release” of the drugs, and therefore the modification of MSN for controlled delivery seems to be a necessary step. Herein, chitosan (CS) was used for the surface functionalization of MSN via amidation reaction, and the introduced CS could function as a “gatekeeper” and the drug of methotrexate (MTX) might be encapsulated in the mesopores of MSN. As a result, the “premature release” of the encapsulated MTX could be effectively circumvented with the aid of the CS cap. More importantly, the drug delivery from the hybrid of MSN and CS (MSN/CS) can be endowed with pH-sensitivity by the introduction of CS because the amide bonding between CS and MSN is highly pH-sensitive. The cumulative release of MTX from the MSN/CS is more pronounced at pH 5.0 (80.86%) than those at pH 6.8 (40.46%) and pH 7.4 (18.25%).     

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH-sensitive drug release property

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH sensitivity were developed for oral delivery of protein drugs, using bovine serum albumin (BSA) as a model drug. The composite drug-loaded microparticles with a mean particle size less than 200 μm were prepared by a convenient shredding method. Since the microparticles were formed by tripolyphosphate cross-linking, electrostatic complexation by alginate and/or pectin, as well as ionotropic gelation with calcium ions, the microparticles exhibited an improved pH-sensitive drug release property. The in vitro drug release behaviors of the microparticles were studied in simulated gastric (pH 1.2 and pH 5.0), intestinal (pH 7.4) and colonic (pH 6.0 and pH 6.8 with enzyme) media. For the composite microparticles with suitable compositions, the releases of BSA at pH 1.2 and pH 5.0 could be effectively sustained, while the releases at pH 7.4, pH 6.8 and pH 6.0 increased significantly, especially in the presence of pectinase. These results clearly suggested that the microparticles had potential for site-specific protein drug delivery through oral administration.     

The selectivity in MEKC of pseudo-stationary phases based on polyelectrolyte complexes: I. composition of the complex

Polyelectrolyte–surfactant complexes (PSC) of polycarboxylic acids with alkyl-trimethylammonium salts look very promising as a new type of pseudo-stationary phase in micellar electrokinetic chromatography. PSC produce an intramolecular micellar phase, and the morphology of the micelles is significantly different from that of the corresponding typical surfactant micelles. Pseudo-stationary phases based on PSC have unique selectivity. In this paper, the effect of the composition () of the PSC of polyacrylic acid (PAA) M_W 130,000 with dodecyltrimethylammonium bromide (DTAB) and of the PSC of PAA M_W 450,000 with DTAB on the separation of DNS–amino acids and phenol derivatives in these systems was investigated. Relative retention and relative selectivity were used to describe the electrophoretic behavior of the amino acids and phenol derivatives. The main advantage of PSC pseudo-phases is that the nature and the structure of micelle-like units, and hence the selectivity of electrophoretic separation, could easily be modified by changing the composition of the complex.     

Nanoparticles based on polyelectrolyte complexes: effect of structure and net charge on the sorption capability for solved organic molecules

 The sorption of solved organic molecules such as p-nitrophenol or dyes on previously formed nanoparticles based on polyelectrolyte/micelle complexes or polycation/polyanion complexes was studied. It could be shown that the sorption capability strongly depends on the structure and properties of the complex particles. Investigations have been made with complex particles that differ in their hydrophobic/hydrophilic structure, size and net charge. Such complex aggregates could be prepared by mixing the cationic surfactant dodecylamido-ethyldimethylbenzylammonium chloride, the polycations poly(diallyldimethylammonium chloride) or poly(methacryloyloxyethyldimethylbenzylammonium chloride) and the copolymers of maleic acid with propene or methylstyrene as anionic components. It is found that the sorption capability increases with increasing molar mass and hydrophobic properties of the components used. In addition, the concentration ratio c _polym/c _org.poll that was required to reach optimal sorption conditions could be decreased by the use of macromolecules with high molar masses. The best results were obtained by using cationic stabilized complex particles formed with high-molar-mass polycations as sorbents for anionic dye molecules. Received: 10 November 1999 Accepted: 24 February 2000     

Uniform chitosan microspheres for potential application to colon-specific drug delivery

Uniform chitosan microspheres have been fabricated and weakly crosslinked for potential applications in colon-specific drug delivery. The effects of microsphere size, crosslinking density and electrostatic interactions between the drug and chitosan on drug release were studied, employing model drugs of different acidities. When the drug was basic, all chitosan spheres exhibited 100% release within 30 min. As the acidity of the drug increased, the release slowed down and depended on the crosslinking density and microsphere size. The release of weakly acidic drug was most suppressed for large spheres (35-38 microm), while the small spheres (23-25 microm) with higher crosslinking exhibited the most retention of highly acidic drug, indicating that they are a promising candidate for colon-specific delivery.     

Development of polyelectrolyte complexes of chitosan and phosphotungstic acid as pervaporation membranes for dehydration of isopropanol

Using a solution technique, chitosan-based polyelectrolyte complexes (PECs) were developed as pervaporation membranes by incorporating phosphotungstic acid (PTA). The resulting membranes were characterized by Fourier transform infrared spectroscopy (FTIR), wide-angle X-ray diffraction (WAXD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). Membranes were tested for their ability to separate water–isopropanol mixtures by pervaporation in the temperature range of 30–50 °C. The experimental results demonstrated that both flux and selectivity were increased simultaneously with increasing PTA content in the membrane. The permeation flux of pure chitosan membrane was increased dramatically from 4.13 to 11.70 × 10⁻² kg/m² h and correspondingly its separation factor was increased from 4490 to 11,241 and then decreased to 7490 at 30 °C for 10 mass% of water in the feed. The total flux and flux of water were found to be almost overlapping particularly for PECs membranes, suggesting that these could be used effectively to break the azeotropic point of water–isopropanol mixtures. From the temperature dependency of diffusion and permeation values, the Arrhenius activation parameters were estimated and discussed in the context of membranes efficiency. The pure chitosan and a small amount of PTA-incorporated PECs membranes exhibited positive heat of sorption while other PECs membranes exhibited negative heat of sorption, giving exothermic contribution.     

Antitumor efficacy of doxorubicin released from crosslinked nanoparticulate chondroitin sulfate/chitosan polyelectrolyte complexes

It is demonstrated that nanoparticulate PEC with a crosslinked shell sustains DOX release and increases DOX activity against cancer cells. CSMA was synthesized to prepare PEC with chitosan. The double bonds among CSMA were used to form a shell crosslink. The released DOX from DOX-loaded PECs against human cancer KB cells and A549 cells were qualitatively traced by confocal laser scanning microscopy and flow cytometry, and quantitatively measured by capillary electrophoresis. All the results implied the DOX-loaded PEC with a crosslinked shell had the best anti-cancer potency of free DOX and the DOX-loaded PEC prepared from pure chondroitin sulfate and chitosan in both the cell lines.     

Novel polyelectrolyte complexes between N-carboxyethylchitosan and synthetic polyelectrolytes

Novel polyelectrolyte complexes (PEC) between the polyampholyte N-carboxyethylchitosan (CECh) and polyacid or polybase have been prepared. The complex formation between CECh and poly(2-acryloylamido-2-methylpropanesulfonic acid) (PAMPS), poly(acrylic acid) (PAA) or poly(ethylene imine) (PEI) has been studied. The complex CECh/PAMPS is formed in the pH range from 1.2 to 6.0. The complex CECh/PAA is formed in the range 4.8-6.0 and CECh/PEI—from pH 5.4 to 7.0. The stoichiometry of the complexes depends on the pH value of the medium. In case of CECh/PAMPS and CECh/PAA the maximum quantity of complex is formed in excess of CECh and in the case of CECh/PEI—in excess of PEI. It has been shown that PEC formation between CECh and PAMPS improves the haemocompatibility of CECh.     

Adsorption of polyelectrolyte multilayers and complexes on silica and cellulose surfaces studied by QCM-D

The adsorption of polyelectrolyte (PE) multilayers and complexes, obtained from both high- and low-charge polyelectrolytes, was studied on silica and on cellulose model surfaces by quartz crystal microbalance with dissipation (QCM-D). The film properties acquired with the different strategies were compared. When polyelectrolytes were added on an oppositely charged surface in sequence to form multilayers both the change in frequency and dissipation increased. The changes in frequency and dissipation were clearly higher if low-charge PEs were used in the multilayer formation. The substrate, silica or cellulose, did not affect the adsorption behaviour of low-charge PEs and only minor differences were seen in the adsorbed amounts and changes in dissipation of high-charge PEs between SiO₂ and cellulose. The complexes formed by low-charge PEs had higher changes in frequency and dissipation at low ionic strength on both surfaces, while the complexes formed from high-charge polyelectrolytes adsorbed more at high salt concentration. The complexes of low-charge polyelectrolytes adsorbed more on silica, while the complexes formed by high-charge PEs formed thicker layers on cellulose. The charge ratio had a significant effect on the adsorption and the highest changes in frequency and dissipation were obtained in the anionic/cationic charge ratio of 0.5–0.6. Generally, the multilayers and complexes formed by low-charge polyacrylamides adsorbed highly and formed rather thick layers on both surfaces, unlike the high-charge PEs which formed thin layers using either one of the addition techniques.     

Synthesis and characterization of novel carboxymethyl chitosan grafted polylactide hydrogels for controlled drug delivery

Novel carboxymethyl chitosan‐polylactide (CMCS‐g‐PLA) hydrogels were prepared by using 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimide hydrochloride/N‐hydroxysuccinimide (EDC/NHS) as crosslinking agent and catalyst at room temperature. Solid‐state ¹³C‐NMR, SEM, and FT‐IR measurements showed that PLA blocks are successfully grafted onto the CMCS main chains. DSC measurements confirmed the effective crosslinking of carboxymethyl chitosan. With increasing the amount of EDC/NHS, the crosslink destiny of CMCS‐g‐PLA copolymers is improved. The swelling ratio of CMCS‐g‐PLA hydrogels is pH dependent, showing a minimum in the pH range of 3 to 5. Rheological studies confirmed the formation of hydrogels. The higher the crosslinking density, the higher the storage modulus of hydrogels. CMCS‐g‐PLA hydrogels only slightly degrade in PBS for 10 days. In the presence of lysozyme, however, hydrogels with low crosslink density are totally degraded in 10 days. Drug release studies show that after 96 h, 95% of thymopentin is released under in vitro conditions. Copyright © 2015 John Wiley & Sons, Ltd.     

Remotely controlled electro-responsive on-demand nanotherapy based on amine-modified graphene oxide for synergistic dual drug delivery

This study focuses on the development of a new electric field responsive graphene oxide (GO) nanoparticle system for on-demand drug delivery. Today, GO is an attractive option adopted in various biological applications for its exclusive features such as flexibility, conductiveness, cost-effectiveness, and external stimuli-responsive nature. It is usual to utilize multiple drugs in cancer treatment. This kind of therapy has lesser side-effects, drug resistance, and is more effective than utilizing only one drug. This study aims to determine low-voltage-controlled dual drug (aspirin and doxorubicin) release from GO surface. Here, we have demonstrated how to control the drug release rate remotely with a handy mobile phone, with zero passive release at idle time. In addition, the study focused to estimate the synergism of aspirin with doxorubicin in the release mechanism from GO in the presence of external voltage, using the spectroscopic method. Moreover, we observed aspirin- and doxorubicin-induced synergistic antitumor activity in MDA-MB 231 (breast cancer cell) in vitro. Thus, our study presents a noble combination of aspirin and doxorubicin that could be utilized for remotely controlled on-demand drug delivery for triple negative breast cancer treatment, using GO as a carrier.     

Chitosan based hybrid hydrogels for drug delivery: Preparation,biodegradation, thermal,and mechanical properties

In the present paper, biodegradable hybrid hydrogels were prepared by using chitosan as a natural polymer and polyurethane containing azomethine as a synthetic polymer for the drug delivery application for 5-fluorouracil. The fabricated hydrogels were characterized via FT-IR and SEM analysis. Besides, the thermal, mechanical, and wettability properties, water uptake, biodegradation, protein absorption, drug loading, and release behaviors of the hybrid hydrogels were studied. The obtained results indicated that the fabricated hybrid hydrogels have exhibited good mechanical, hydrophilic, water uptake, and biodegradation behaviors. The hybrid hydrogels also showed 50% drug release amounts and they could be a good candidate for the controlled delivery of 5-FU due to these properties.     

Polypeptide dendrimers: Self-assembly and drug delivery

Amphiphilic dendritic poly(glutamic acid)-b-polyphenylalanine copolymers were synthesized using generation 3 dendritic poly(glutamic acid) as the macroinitiator in the ring-opening polymerization of NCA-Phe.The block copolymers self-assembled micelles with polyphenylalanine segments as core and dendritic poly(glutamic acid) segments as shell.The biocompatibility of the micelles was studied.The release of the anticancer drug doxorubicin from the micelles was investigated in vitro.The results showed that the ...     

Recent advances in biopolymer based electrospun nanomaterials for drug delivery systems

Drug delivery systems, including liposomes, gels, prodrugs, and so forth, are used to enhance the tissue benefit of a pharmaceutical drug or conventional substance at a specific diseased site with little toxicological impact. Nanotechnology can be a rapidly developing multidisciplinary science that enables the production of polymers at the manometer scale for different medical applications. The use of biopolymers in drug delivery systems provides compatibility, biodegradability and low immunogenicity biologically. Large-scale and smaller-than-expected medication particles can be delivered using biopolymers such as silk fibroins, collagen, gelatine, and others that are easily formed into suspensions. These drug carrier systems are functional at improving drug delivery and can be used in intranasal, transdermal, dental, and ocular delivery systems. This study discusses the latest developments in drug delivery methods based on nanomaterials, mainly using biopolymers like proteins and polysaccharides.     

Protein delivery based on uncoated and chitosan-coated mesoporous silicon microparticles

Mesoporous silicon is a biocompatible, biodegradable material that is receiving increased attention for pharmaceutical applications due to its extensive specific surface. This feature enables to load a variety of drugs in mesoporous silicon devices by simple adsorption-based procedures. In this work, we have addressed the fabrication and characterization of two new mesoporous silicon devices prepared by electrochemistry and intended for protein delivery, namely: (i) mesoporous silicon microparticles and (ii) chitosan-coated mesoporous silicon microparticles. Both carriers were investigated for their capacity to load a therapeutic protein (insulin) and a model antigen (bovine serum albumin) by adsorption. Our results show that mesoporous silicon microparticles prepared by electrochemical methods present moderate affinity for insulin and high affinity for albumin. However, mesoporous silicon presents an extensive capacity to load both proteins, leading to systems were protein could represent the major mass fraction of the formulation. The possibility to form a chitosan coating on the microparticles surface was confirmed both qualitatively by atomic force microscopy and quantitatively by a colorimetric method. Mesoporous silicon microparticles with mean pore size of 35 nm released the loaded insulin quickly, but not instantaneously. This profile could be slowed to a certain extent by the chitosan coating modification. With their high protein loading, their capacity to provide a controlled release of insulin over a period of 60-90 min, and the potential mucoadhesive effect of the chitosan coating, these composite devices comprise several features that render them interesting candidates as transmucosal protein delivery systems.