Chitosan-based nanoparticle co-delivery of docetaxel and curcumin ameliorates anti-tumor chemoimmunotherapy in lung cancer.

The application of traditional chemotherapy drugs for lung cancer has obvious limitations, such as toxic side effects, uncontrolled drug-release, poor bioavailability, and drug-resistance. Thus, to address the limitations of free drugs and improve treatment effects, we developed novel T7 peptide-modified nanoparticles (T7-CMCS-BAPE, CBT) based on carboxymethyl chitosan (CMCS), which is capable of targeted binding to the transferrin receptor (TfR) expressed on lung cancer cells and precisely regulating drug-release according to the pH value and reactive oxygen species (ROS) level. The results showed that the drug-loading content of docetaxel (DTX) and curcumin (CUR) was approximately 7.82% and 6.48%, respectively. Good biosafety was obtained even when the concentration was as high as 500 µg/mL. More importantly, the T7-CMCS-BAPE-DTX/CUR (CBT-DC) complexes exhibited better in vitro and in vivo anti-tumor effects than DTX monotherapy and other nanocarriers loaded with DTX and CUR alone. Furthermore, we determined that CBT-DC can ameliorate the immunosuppressive micro-environment to promote the inhibition of tumor growth. Collectively, the current findings help lay the foundation for combinatorial lung cancer treatment.

Polyvinyl Alcohol/Chitosan Single-Layered and Polyvinyl Alcohol/Chitosan/Eudragit RL100 Multi-layered Electrospun Nanofibers as an Ocular Matrix for the Controlled Release of Ofloxacin: an In Vitro and In Vivo Evaluation.

A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0-96 for the nanofibers was 9-20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.

An overview of chitosan and its application in infectious diseases.

Infectious diseases, such as the coronavirus disease-19, SARS virus, Ebola virus, and AIDS, threaten the health of human beings globally. New viruses, drug-resistant bacteria, and fungi continue to challenge the human efficacious drug bank. Researchers have developed a variety of new antiviral and antibacterial drugs in response to the infectious disease crisis. Meanwhile, the development of functional materials has also improved therapeutic outcomes. As a natural material, chitosan possesses good biocompatibility, bioactivity, and biosafety. It has been proven that the cooperation between chitosan and traditional medicine greatly improves the ability of anti-infection. This review summarized the application and design considerations of chitosan-composed systems for the treatment of infectious diseases, looking forward to providing the idea of infectious disease therapy.

Evaluation of hyaluronic acid nanoparticle embedded chitosan-gelatin hydrogels for antibiotic release.

The development of chitosan-gelatin (CS-G) hydrogels embedded with ampicillin-loaded hyaluronic acid nanoparticles (HA-NPs) for wound dressing is proposed. It was aimed to provide controlled ampicillin delivery by incorporation of HA-NPs into biocompatible CS-G hydrogel structure. According to in vitro ampicillin release studies, 55% of ampicillin was released from CS-G/HA-NPs hydrogels after 5 days. Antibacterial performance of CS-G/HA-NPs hydrogels was proven with agar disc diffusion test. For cytotoxicity assay, fibroblast cell viability increased in CS-G/HA-NPs hydrogels compared with CS-G group after 24 hr incubation. Consequently, the potential ability of CS-G/HA-NPs hydrogels as a controlled drug delivery system has been verified.

Chitosan mediated solid lipid nanoparticles for enhanced liver delivery of zedoary turmeric oil in vivo.

Zedoary turmeric oil (ZTO) has a strong antitumor activity. However, its volatility, insolubility, low bioavailability, and difficulty of medication owing to oily liquid limit its clinical applications. Solid lipid nanoparticles can provide hydrophobic environment to dissolve hydrophobic drug and solidify the oily active composition to decrease the volatility and facilitate the medication. Chitosan has been widely used in pharmaceutics in recent years and coating with chitosan further enhances the internalization of particles by cells due to charge attract. Here, Chitosan (CS)-coated solid lipid nanoparticles (SLN) loaded with ZTO was prepared and characterized using dynamic laser scanner (DLS) and transmission electron microscope (TEM). The uptake and distribution of drug were evaluated in vitro and in vivo. The average sizes of ZTO-SLN and CS-ZTO-SLN were 134.3 ± 3.42 nm and 210.7 ± 4.59 nm, respectively. CS coating inverted the surface charge of particles from -8.93 ± 1.92 mV to +9.12 ± 2.03 mV. The liver accumulation of CS-ZTO-SLN was higher than ZTO-SLN (chitosan-uncoated particles) by analysis of tissue homogenate using HPLC, and the bioavailability of ZTO was also obviously improved. The results suggested that SLN coated with CS improved the features of ZTO formulation and efficiently deliver drug to the liver.

Phytosome complexed with chitosan for gingerol delivery in the treatment of respiratory infection: In vitro and in vivo evaluation.

Respiratory infection is a viral spreading disease and a common issue, particularly in kids. The treatments are available but have so many limitations because the drawback of this disease is more morbidity and mortality in the severely immune compromised. Even, the phyto-constituent antibacterial drug Gingerol was selected to treat respiratory infection but it exhibits low bioavailability profile, less aqueous-solubility issue and most important is rapidly eliminated from the body. To overcome these problems, novel drug delivery (nanoparticle) based phytosome complexed with chitosan approach was implemented. In this research work, the phytosome (GP) was prepared by blending of gingerol with soya lecithin in organic solvent using anti-solvent precipitation technique and it was further loaded in the aqueous solution of chitosan to formulate the phytosome complexed with chitosan (GLPC). To optimize the formulations of gingerol, it was characterized for percentage yield, percentage entrapment efficiency, drug loading and particle size, physical compatibility studies etc. which demonstrated the confirmation of complex of GLPC with soya lecithin and chitosan. The % entrapment efficiency and % drug loading of GLPC was found (86.02 ±â€¯0.18%, 08.26 ±â€¯0.72%) and of GP (84.36 ±â€¯0.42%, 08.05 ±â€¯0.03%), respectively. The average particle size and zeta potential of GLPC and GP were 254.01 ±â€¯0.05 nm (-13.11 mV), and 431.21 ±â€¯0.90 nm (-17.53 mV), respectively which confirm the inhibition of particle aggregation by using chitosan in complex. The in vitro release rate of GP (86.03 ±â€¯0.06%) was slower than GLPC (88.93 ±â€¯0.33%) in pH 7.4 phosphate buffer up to 24 h by diffusion process (Korsmeyer Peppas model). The optimized GLPC and GP were shown irregular particle shapes & spherical and oval structures with smooth surface by SEM analysis. Furthermore, GLPC has shown the potent in vitro antioxidant activity, susceptible antibacterial activity and effective anti-inflammatory activity as compared to GP against stress, microbial infection and inflammation which were causable reason for the respiratory infections. GLPC has improved the significant bioavailability and also correlated the hematological values on rabbit blood against the incubation of microorganisms. Thus, the prepared nanoparticle based approach to deliver the gingerol, has the combined effect of chitosan and phytosome which shown better sustained-release profile and also prolonging the oral absorption rate of gingerol with effective antibacterial activity to treat respiratory infection.

Functional Chitosan Nanoparticles in Cancer Treatment.

With exponential growth in nanotechnology and material chemistry, the application of a variety of nanomaterials in biomedical field has attracted increasing interest, especially in cancer diagnosis and treatment. Nanoparticles have greatly revolutionized the therapy pattern of cancer owing to their specific targeting ability, prolonged circulation time, enhanced therapeutic efficacy, and decreased systemic side effects. Chitosan, a modified natural polysaccharide with excellent biocompatibility, has been intensively studied for use as carriers to deliver various drugs and genes in cancer treatment. This review provides an insight into the advances in chitosan-based nanoparticles with a focus on its therapeutic potential in cancer treatment.

Development and evaluation of alginate-chitosan gastric floating beads loading with oxymatrine solid dispersion.

Oxymatrine (OM) can be metabolized to matrine in gastrointestinal ileocecal valve after oral administration, which affects pharmacological activity and reduce bioavailability of OM. A type of multiple-unit alginate-chitosan (Alg-Cs) floating beads was prepared by the ionotropic gelation method for gastroretention delivery of OM. A solid dispersion technique was applied and incorporated into beads to enhance the OM encapsulation efficiency (EE) and sustain the drug release. The surface morphology and internal hollow structure of beads were evaluated using optical microscopy and scanning electron microscopy (SEM). The developed Alg-Cs beads were spherical in shape with hollow internal structure and had particle size of 3.49 ± 0.09 mm and 1.33 ± 0.09 mm for wet and dried beads. Over 84% of the optimized OM solid dispersion-loaded Alg-Cs beads were able to continuously float over the simulated gastric fluid for 12 h in vitro. The OM solid dispersion-loaded Alg-Cs beads showed drug EE of 67.07%, which was much higher than that of beads loading with pure OM. Compared with the immediate release of OM capsules and pure OM-loaded beads, the release of OM from solid dispersion-loaded Alg-Cs beads was in a sustained-release manner for 12 h. Prolonged gastric retention time of over 8.5 h was achieved for OM solid dispersion-loaded Alg-Cs floating beads in healthy rabbit in in vivo floating ability evaluated by X-ray imaging. The developed Alg-Cs beads loading with OM solid dispersion displayed excellent performance features characterized by excellent gastric floating ability, high drug EE and sustained-release pattern. The study illustrated the potential use of Alg-Cs floating beads combined with the solid dispersion technique for prolonging gastric retention and sustaining release of OM, which could provide a promising drug delivery system for gastric-specific delivery of OM for bioavailability enhancement.

Curcumin-Loaded Chitosan-Coated Nanoparticles as a New Approach for the Local Treatment of Oral Cavity Cancer.

Mucoadhesive nanoparticles loaded with curcumin were developed as a new approach to deliver curcumin for the local treatment of oral cancer. PCL nanoparticles coated with chitosan displaying different molar masses were prepared by using the nanoprecipitation technique. The mucoadhesive properties of nanoparticle suspensions were demonstrated by their strong ability to interact with the glycoprotein mucin through electrostatic interactions. Similar permeation profiles of curcumin loaded in uncoated and chitosan-coated nanoparticles across porcine esophageal mucosa were verified. Curcumin concentrations retained in the mucosa suggest the possibility of a local effect of the drug. In vitro studies demonstrated that free curcumin.and curcumin loaded into nanoparticles coated with chitosan caused significant reduction of SCC-9 human oral cancer cell viability in a concentration and time-dependent manner. However, no significant cell death was observed after 24 h of treatment with unloaded nanoparticles coated with chitosan. In addition, curcumin-loaded nanoparticles showed reduced cytotoxicity, when compared with the free drug. Therefore, chitosan-coated PCL nanoparticles may be considered a promising strategy to deliver curcumin directly into the oral cavity for the treatment of oral cancer.

Development and evaluation of chitosan and chitosan derivative nanoparticles containing insulin for oral administration.

Chitosan and chitosan derivative-based nanoparticles loaded with insulin were prepared by self-assembly, via electrostatic interactions between the negatively charged drug and the positively charged polymers. In the investigated chitosan derivatives, the amine groups were substituted to different extents (33, 52 or 99%) by 2-hydroxypropyl-3-trimethyl ammonium groups, rendering the polymers permanently positively charged, irrespective of the pH. This is an important property for this type of advanced drug delivery system, since the pH value changes throughout the gastrointestinal tract and electrostatic interactions are of crucial importance for the stability of the nanoparticles. Permanent positive charges are also in favor of mucoadhesion. In contrast, the electric charges of chitosan molecules depend on the pH of the surrounding medium. Since the solubility of the chitosan derivatives increased due to the introduction of quaternary ammonium groups, sodium tripolyphosphate (TPP) was added to the systems to create supplementary cross-links and stabilize the nanoparticles. The presence of TPP influenced both the dissolution of the polymer matrix as well as the resulting release kinetics. The underlying drug release mechanisms were found to be more complex than simple diffusion under constant conditions, likely involving also ionic interactions and matrix dissolution. The most promising formulation was based on a chitosan derivative with 33% substitution degree and characterized by a Z-average of 142 ± 10 nm, a zeta potential of 29 ± 1 mV, an encapsulation efficacy of 52 ± 3% and, most importantly, the release of insulin was sustained for more than 210 min.

Enhanced oral delivery of curcumin from N-trimethyl chitosan surface-modified solid lipid nanoparticles: pharmacokinetic and brain distribution evaluations.

PURPOSE: Solid lipid nanoparticles (SLNs) have been proposed as a colloidal carrier system that could enhance the oral bioavailability of curcumin. However, a burst release of the loaded drug, which occurs in acidic environments, has been a main obstacle to the oral delivery of curcumin by using SLNs as a carrier system. We hypothesized that a quarternized chitosan derivative could be used for acid-resistant coating to stabilize the SLNs and circumvent the burst release. METHODS: N-trimethyl chitosan (TMC) was synthesized and determined by (1)H-NMR and FT-IR. To investigate the details of chitosan and TMC surface modification on SLCNs composed of palmitic acid, cholesterol, TPGS and curcumin, a number of factors such as optimized SLNs composition, solid state characterization, stability, cell viability, in vitro release in GI conditions, curcumin oral bioavailability and brain distribution studies, were evaluated. RESULTS: The TMC-SLCNs exhibited prolonged stability in room and refrigerated conditions, controlled drug release in simulated intestinal fluid, significantly higher oral bioavailability, and brain distribution of curcumin than free curcumin, chitosan and non-coated SLCNs. CONCLUSIONS: These finding suggests that the TMC-SLCNs is a promising nanocarrier system for oral delivery and brain distribution of curcumin.

Combinatorial anticancer effects of curcumin and 5-fluorouracil loaded thiolated chitosan nanoparticles towards colon cancer treatment.

BACKGROUND: Evaluation of the combinatorial anticancer effects of curcumin/5-fluorouracil loaded thiolated chitosan nanoparticles (CRC-TCS-NPs/5-FU-TCS-NPs) on colon cancer cells and the analysis of pharmacokinetics and biodistribution of CRC-TCS-NPs/5-FU-TCS-NPs in a mouse model. METHODS: CRC-TCS-NPs/5-FU-TCS-NPs were developed by ionic cross-linking. The in vitro combinatorial anticancer effect of the nanomedicine was proven by different assays. Further the pharmacokinetics and biodistribution analyses were performed in Swiss Albino mouse using HPLC. RESULTS: The 5-FU-TCS-NPs (size: 150±40nm, zeta potential: +48.2±5mV) and CRC-TCS-NPs (size: 150±20nm, zeta potential: +35.7±3mV) were proven to be compatible with blood. The in vitro drug release studies at pH4.5 and 7.4 showed a sustained release profile over a period of 4 days, where both the systems exhibited a higher release in acidic pH. The in vitro combinatorial anticancer effects in colon cancer (HT29) cells using MTT, live/dead, mitochondrial membrane potential and cell cycle analysis measurements confirmed the enhanced anticancer effects (2.5 to 3 fold). The pharmacokinetic studies confirmed the improved plasma concentrations of 5-FU and CRC up to 72h, unlike bare CRC and 5-FU. CONCLUSIONS: To conclude, the combination of 5-FU-TCS-NPs and CRC-TCS-NPs showed enhanced anticancer effects on colon cancer cells in vitro and improved the bioavailability of the drugs in vivo. GENERAL SIGNIFICANCE: The enhanced anticancer effects of combinatorial nanomedicine are advantageous in terms of reduction in the dosage of 5-FU, thereby improving the chemotherapeutic efficacy and patient compliance of colorectal cancer cases.

Development and optimization of curcumin-loaded mannosylated chitosan nanoparticles using response surface methodology in the treatment of visceral leishmaniasis.

OBJECTIVE: The study aims at formulation and optimization of macrophage-targeted curcumin-loaded mannosylated chitosan nanoparticles (Cur-MCNPs) of curcumin (CUR) to improve its therapeutic potential in the treatment of visceral leishmaniasis (VL). METHODS: Response surface methodology (RSM) using central composite design was employed to study the effect of formulation factors on physicochemical-dependent characteristics. Chitosan was coupled with d-mannose, by reductive amination, to prepare a mannosylated chitosan, a conjugate polymer and a subsequent formulation of Cur-MCNPs. Optimized formulation prepared using RSM was evaluated for in vitro release kinetics at physiological pH 7.4 and endosomal macrophage pH 4.5; in vivo pharmacokinetic profile and targeting potential were evaluated by fluorescence microscopy. RESULTS: Optimized Cur-MCNPs exhibited spherical and smooth surface with a mean particle size of 215 nm, polydispersity index of 0.381, zeta potential of + 24.37 mV and % entrapment efficiency of 82.12%. The pharmacokinetic study of optimized Cur-MCNPs showed significant improvement in the value of mean resident time (39.38 h) compared to free CUR solution (0.30 h) (p < 0.05). In vivo uptake study indicated that endocytosis took place effectively within the macrophages of reticuloendothelial system. CONCLUSIONS: Thus, Cur-MCNPs could be considered as a promising delivery strategy towards active targeting of CUR to macrophages for the effective treatment of VL.

Preparation and evaluation of antigen/N-trimethylaminoethylmethacrylate chitosan conjugates for nasal immunization.

The frequent outbreak of respiratory infectious diseases such as influenza and pulmonary tuberculosis calls for new immunization strategies with high effectiveness. Nasal immunization is one of the most potential methods to prevent the diseases infected through the respiratory tract. In this study, we designed a water-soluble system based on antigen/N-trimethylaminoethylmethacrylate chitosan conjugates for nasal immunization. N-trimethylaminoethylmethacrylate chitosan (TMC) was synthesized by free radical polymerization of chitosan and N-trimethylaminoethylmethacrylate chloride and identified by (1)H NMR and FT-IR. Thiolated ovalbumin (OVA) was covalently conjugated to maleimide modified TMC with high conjugation efficiency. OVA conjugated TMC (OVA-TMC) significantly increased uptake of OVA by Raw 264.7 cells, which was 2.38 times higher than that of OVA/TMC physical mixture (OVA+TMC) at 4h. After nasal administration, OVA-TMC showed higher transport efficiency to superficial and deep cervical lymph nodes than OVA+TMC or OVA alone. Balb/C mice were intranasally given with OVA-TMC three times at 2-week internals to evaluate the immunological effect. The serum IgG, IgG1 and IgG2a levels of the OVA-TMC group were 17.9-87.9 times higher than that of the OVA+TMC group and comparable to that of the intramuscular group. The secretory IgA levels in nasal wash and saliva of the OVA-TMC group were 5.2-7.1 times higher than that of the OVA+TMC group while the secretory IgA levels of the intramuscular alum-precipitated OVA group were not increased. After immunofluorescence staining of nasal cavity, IgA antibody secreting cells were mainly observed in the lamina propria regions and glands of nasal mucosa. OVA-TMC showed little toxicity to the nasal epithelia or cilia of rats after nasal administration for three consecutive days. These results demonstrated that antigen conjugated TMC can induce both systemic and mucosal immune responses after nasal administration and may serve as a convenient, safe and effective vaccine for preventing respiratory infectious diseases.

Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella.

OBJECTIVES: The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan-dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella. METHODS: The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model. RESULTS: In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection. CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration. CONCLUSIONS: CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection. This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.

Gadolinium-loaded chitosan nanoparticles as magnetic resonance imaging contrast agents for the diagnosis of tumor.

The aim of our study was to prepare gadolinium loaded chitosan nanoparticles (Gd-CSNPs) for magnetic resonance imaging (MRI). The chitosan nanoparticles (CSNPs) were prepared by ionic gelation method with sodium tripolyphosphate. The Gd ions were conjugated to the surface of CSNPs through diethylenetriamine pentaacetic acid (DTPA) using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to obtain Gd-CSNPs. The physicochemical properties of CSNPs and Gd-CSNPs were measured by transmission electron microscope, dynamic light scattering and inductively coupled plasma optical emission spectroscopy, respectively. The cell toxicity evaluation was performed in mouse B16 cells by MTT assay. The T1-weighed magnetic resonance images were measured by a 3.0 T Sigma scanner. The morphologies of the CSNPs and Gd-CSNPs were spherical or ellipsoidal in shape. The mean sizes of the CSNPs and Gd-CSNPs were 110.9 +/- 6.8 nm and 153.0 +/- 7.5 nm, respectively. The zeta potentials of the CSNPs and Gd-CSNPs were 22.30 +/- 0.77 mV and 13.91 +/- 4.26 mV, respectively. The relaxation rates of Gd-CSNPs and Magnevist were 7.509 mM(-1) x s(-1) and 3.052 mM(-1) x s(-1), respectively. The Gd-CSNPs exhibited high T1 relaxivity and no obvious cytotoxicity was observed under the experimental concentrations in mouse B16 melanoma cells. These results indicated that the Gd-CSNPs had great potential as MRI contrast agents for the early diagnosis of tumor.

Comparison of PLGA and lecithin/chitosan nanoparticles for dermal targeting of betamethasone valerate.

Poly(lactide-co-glycolide) (PLGA) and lecithin/chitosan (LC) nanoparticles were prepared to evaluate the difference in the behavior upon administration on skin, for steroidal treatment. For this purpose, betamethasone-17-valerate (BMV)-loaded nanoparticles with a narrow size distribution and high entrapment efficiency were prepared. Permeation studies showed that both polymeric nanoparticles enhanced the amount of BMV in epidermis, which is the target site of topical steroidal treatment, when compared with commercial formulation. 1.58-Fold increase was determined in the epidermis concentration of BMV by LC nanoparticles with respect to PLGA nanoparticles. Nanoparticles were diluted in chitosan gel (10%, w/w) to prepare suitable formulation for topical application. Accumulation from both gel formulations were found significantly higher than commercial formulation in skin layers (p < 0.05). In addition, pharmacodynamic responses were also investigated as anti-inflammatory and skin-blanching parameters. Both formulations significantly improved these parameters although they contained 10 times less amount of BMV than commercial cream. Moreover, TEWL measurement exhibited no barrier function changes upon the application of nanoparticles on skin. Overall, both nanoparticles improved the localization of BMV within skin layers; but when compared with PLGA nanoparticles, the LC nanoparticles could be classified as a better candidate for topical delivery vehicle in the treatment of various dermatological inflammatory diseases.

Near-infrared fluorescing IR820-chitosan conjugate for multifunctional cancer theranostic applications.

This study reports the preparation and characterization of IR820-chitosan conjugates that have potential multifunctional imaging-hyperthermia applications in cancer. The conjugates were formulated by covalentcouplingofchitosan to a carboxyl derivatized IR820, and studied for optical imaging and hyperthermia applications. IR820-chitosan conjugates were able to generate heat upon exposure to 808nm laser and produce hyperthermic cell growth inhibition in cancer cell lines MES-SA, SKOV-3 and Dx5. The level of cell growth inhibition caused by hyperthermia was significantly higher for IR820-chitosan compared to IR820 in MES-SA and Dx5 cells. Fluorescent microscope images of these cancer cell lines after 3-h exposure to 5µM IR820-chitosan showed that the conjugates can be used for in vitro near-infrared imaging. In an in vivo rat model, the conjugates accumulated in the liver after i.v. injection and were excreted through the gastrointestinal tract, demonstrating a different biodistribution when compared to the free dye. The accumulation of these conjugates in bile with subsequent gastrointestinal excretion allows for potential applications as gastrointestinal contrast agents and delivery vehicles. This formulation can potentially be used in multifunctional cancer theranostics.

Exploiting the synergistic effect of chitosan-EDTA conjugate with MSA for the early recovery from colitis.

The present study was aimed to exploit the antibacterial/antifungal and film coating potential of Chitosan-EDTA (CH-EDTA) conjugate in combination with mesalamine (anti-inflammatory agent) for the early recovery from TNBS induced coilitis. The results suggested CH:EDTA (1:1) spray coated mesalamine tablets has an ability to transport drug in buffer pH 6.8 with rat caecal content condition. The CH-EDTA shows high level of adhesiveness of coat with core tablet. Further, FTIR, DSC and SEM analysis suggested spray coating of CH-EDTA on tablets was beneficial as compared to ladling method as it enhances interaction density and showed resistance from pH (1.2, 6.8 and 7.4). The pharmacokinetic parameters, AUC and AUMC of spray coated tablets were respectively, 4.70 fold and 2.10 fold increased. A synergistic therapeutic effect with CH-EDTA spray coated mesalamine was observed as evaluated by colon/body weight ratio, clinical activity score and damage score. X ray image study supported that CH-EDTA conjugate successfully delivered MSA tablets to large intestine. Histopathology of colon tissues showed rapid recovery from TNBS induced colitis in rats within 4 days. The findings revealed decreased recovery period was due to combined effect of both CH-EDTA and MSA to treat TNBS induced colitis.

S-protected thiolated chitosan: synthesis and in vitro characterization.

Purpose of the present study was the generation and evaluation of novel thiolated chitosans, so-named S-protected thiolated chitosans as mucosal drug delivery systems. Stability of all conjugates concerning swelling and disintegration behavior as well as drug release was examined. Mucoadhesive properties were evaluated in vitro on intestinal mucosa. Different thiolated chitosans were generated displaying increasing amounts of attached free thiol groups on the polymer, whereby more than 50% of these thiol groups were linked with 6-mercaptonicotinamide. Based on the implementation of this hydrophobic residue, the swelling behavior was 2-fold decreased, whereas stability was essentially improved. Their mucoadhesive properties were 2- and 14-fold increased compared to corresponding thiolated and unmodified chitosans, respectively. Release studies out of matrix tablets comprising the novel conjugates revealed a controlled release of a model peptide. Accordingly, S-protected thiomers represent a promising type of mucoadhesive polymers for the development of various mucosal drug delivery systems.