Chitosan For Delivery Research Articles

Advances in Chitosan Derivatives: Preparation, Properties and Applications in Pharmacy and Medicine

Chitosan (CS) derivatives have been extensively investigated to enhance the physicochemical and biological properties of CS, such as its solubility, biocompatibility, and bioactivity, which are required in various areas of pharmacy and medicine. The present work emphasizes the ongoing research and development in this field, suggesting that the further exploration of CS derivatives could lead to innovative solutions that benefit society. The physicochemical properties, biological activities, methods of preparation, advantages, limitations, intended application areas, and realized practical implementations of particular CS derivatives are summarized and discussed herein. Despite the numerous promising attributes of CS derivatives as reported in this paper, however, challenges like target selectivity, standardization (purity, chitosan structural variability), and cost-effectiveness still need addressing for widespread implementation, especially in drug delivery. Therefore, basic research studies still prevail in CS drug delivery systems. However, for specific applications such as wound healing and tissue engineering, implementations of CS derivatives in practice are found to be more frequent. To obtain a more complex view of the topic, information from the scientific papers reviewed is supplemented with information from actual patents and clinical studies. Both basic research advances and the most successful and important medical implementations of CS derivatives are discussed concerning further challenges and future perspectives.

Exploring the promising role of chitosan delivery systems in breast cancer treatment: A comprehensive review

Breast cancer presents a significant global health challenge, driving the development of novel treatment strategies for therapeutic interventions. Nanotechnology has emerged as a promising avenue for addressing this challenge, with Chitosan (CS) nanoparticles receiving prominence due to their unique characteristics and multitude of potential applications. This review provides a comprehensive overview of the role of Chitosan nanoparticles in breast cancer therapy. The review begins by emphasizing the prevalence and importance of breast cancer as a major health issue, underscoring the necessity for effective treatments. It then delves into the application of Chitosan nanoparticles in breast cancer therapy. One key aspect discussed is their role as carriers for anticancer drugs, enabling targeted delivery and improved cellular uptake. Furthermore, the review explores modified Chitosan nanoparticles and strategies for enhancing their efficacy and specificity in breast cancer treatment. It also examines Chitosan conjugates and hybrids, which offer innovative approaches for combination therapy. Additionally, metal and magnetic Chitosan nanoparticles are discussed spanning their capacity to assist in imaging, hyperthermia, as well as targeted drug delivery. In conclusion, the review summarizes the current research landscape regarding Chitosan nanoparticles for breast cancer therapy and offers insights into future directions. Overall, the review highlights the versatility, potential benefits, and future prospects of Chitosan nanoparticles in combating breast cancer.

Chitosan-TPP microcapsules for controlled drug release

Production of chitosan/sodium tripolyphosphate (CS/TPP) microcapsules via spray drying involves atomizing an emulsion containing CS, TPP, acetic acid (AcOH), and folic acid (FA) into fine droplets exposed to high-temperature, low-pressure gas flow. Solvent evaporation within the drying chamber leads to solid particle formation. Spray drying is valuable for creating solid CS/TPP microcapsules. Precise equipment parameter adjustments, like inlet temperature and gas flow rate, enable the study of microcapsule morphology, size, and properties. This adaptability allows for customization to specific pH dissolution ranges. The production method's impact on CS/TPP microcapsules was studied by modifying spray drier parameters, including inlet temperature and aspirator pressure, to enhance understanding of their behavior in solution under varied production conditions.
 In chitosan delivery systems, various approaches can encapsulate drug agents like folic acid, an analog to the cancer treatment drug methotrexate. Agents can be added to the chitosan solution pre-crosslinking, incorporated into gelation-inducing agents pre-mixing with chitosan, or included in the crosslinking mixture. Experiments were conducted to assess CS/TPP microcapsules' behavior when encapsulating agents like folic acid. Release profiles were analyzed to understand their drug delivery capabilities and potential as controlled release carriers.

Chitosan-Based Hydrogels for Controlled Delivery of Asiaticoside-Rich Centella asiatica Extracts with Wound Healing Potential.

Centella asiatica extract is a valued plant material with known anti-inflammatory and anti-microbiological properties. Using the Design of Experiment (DoE) approach, it was possible to obtain an optimized water/alcoholic extract from Centella asiatica, which allowed the preparation of the final material with biological activity in the wound healing process. Studies on the novel applications of Centella asiatica in conjunction with the multifunctional chitosan carrier have been motivated by the plant's substantial pharmacological activity and the need to develop new and effective methods for the treatment of chronic wounds. The controlled release of asiaticoside was made possible by the use of chitosan as a carrier. Based on the findings of investigations using the PAMPA skin assay, which is a model imitating the permeability of actives through skin, this compound, characterized by sustained release from the chitosan delivery system, was identified as being well able to permeate biological membranes such as skin. Chitosan and the lyophilized extract of Centella asiatica worked synergistically to block hyaluronidase, exert efficient microbiological activity and take part in the wound healing process, as proven in an in vitro model. A formulation containing 3% extract with 3% medium-molecular-weight chitosan was indicated as a potentially new treatment with high compliance and effectiveness for patients. Optimization of the chitosan-based hydrogel preparation ensured the required rheological properties necessary for the release of the bioactive from the chitosan delivery system and demonstrated a satisfactory antimicrobial activity.

Wettability, Drug Delivery, Biodegradability, and Mechanical Strength of Chitosan–Gelatin Polymer Hydrogels Treated with Atmospheric Pressure DBD Plasma

Wettability, Drug Delivery, Biodegradability, and Mechanical Strength of Chitosan–Gelatin Polymer Hydrogels Treated with Atmospheric Pressure DBD Plasma

Ecofriendly System Based on Mesoporous Silica Nanoparticles Delivery of Chitosan to Control Soft Rot Disease and Maintain Postharvest Quality of Tuber Potato

Ecofriendly System Based on Mesoporous Silica Nanoparticles Delivery of Chitosan to Control Soft Rot Disease and Maintain Postharvest Quality of Tuber Potato

KNOWLEDGE EVOLUTION IN NANOCHITOSAN RESEARCH AND INNOVATIVE BIOTECHNOLOGICAL APPLICATIONS: A MULTINATIONAL ASSESSMENT FOR NOWCAST AND FUTURE FORECAST

There had been a growing global need for biomolecular agents due to its diversity in biotechnological application especially chitosan and its derivatives. Current advances in nano-particulate technologies have also abetted the use of biomolecular-based nano-type delivery and functions of chitosan resulting nano-based chitosan/nanochitosan particle. Although there exist notable advances in the exploration and innovative nanochitosan application, future expansion remains bleary. The current study access the knowledge evolution in nanochitosan research and innovative biotechnological applications via science mapping of previous studies from authors, institutions, countries, collaboration networks, and productivity. Retrieved documents were 5,923 with 13,327 authors, from Web of Science (WoS) Core Collection and timespan of 1990 – 2019 using the search title; (Chitosan and nanoparticle*). Our result reveals an increase in the publication of related documents in fifth yearly order. This notable/significant increase observed in subsequent years was revealed by the Lotka’s model with an annual growth rate of 33.32%; Lotka's model beta=1.927; C=0.286; R2=0.89; p.value=0.05. Corresponding Author's Countries were China 1756 (29.65), India 683 (11.53), Japan 47 (0.79); while country citation are; China (51720), India (17595), Korea (10688), Australia (1679). The last decade reports reveal more publications on nanochitosan studies ranging from 238 publications to greater than 746 publications. Although such increase has revealed global known capabilities, research based and/or application of the nanobased-chitosan, there is need for pertinent exploitation of nanochitosan potentials, documentation, application, progresses and future of related studies. A suggestive continuous application of such progresses on chitosan knowledge-research based documentation/exploration has a part with global future research and biotechnological application.

Cytotoxicity Enhancement in MCF-7 Breast Cancer Cells with Depolymerized Chitosan Delivery of α-Mangostin.

The application of α-mangostin (AMG) in breast cancer research has wide intentions. Chitosan-based nanoparticles (CSNPs) have attractive prospects for developing anticancer drugs, especially in their high flexibility for modification to enhance their anticancer action. This research aimed to study the impact of depolymerized chitosan (CS) on the cytotoxicity enhancement of AMG in MCF-7 breast cancer cells. CSNPs effectivity depends on size, shape, crystallinity degree, and charge surface. Modifying CS molecular weight (MW) is expected to influence CSNPs’ characteristics, impacting size, shape, crystallinity degree, and charge surface. CSNPs are developed using the method of ionic gelation with sodium tripolyphosphate (TPP) as a crosslinker and spray pyrolysis procedure. Nanoparticles’ (NPs) sizes vary from 205.3 ± 81 nm to 450.9 ± 235 nm, ZP charges range from +10.56 mV to +51.56 mV, and entrapment efficiency from 85.35% to 90.45%. The morphology of NPs are all the same spherical forms. In vitro release studies confirmed that AMG–Chitosan–High Molecular Weight (AMG–CS–HMW) and AMG–Chitosan–Low Molecular Weight (AMG–CS–LMW) had a sustained-release system profile. MW has a great influence on surface, drug release, and cytotoxicity enhancement of AMG in CSNPs to MCF-7 cancer cells. The preparations AMG–CS–HMW and AMG–CS–LMW NPs considerably enhanced the cytotoxicity of MCF-7 cells with IC50 values of 5.90 ± 0.08 µg/mL and 4.90 ± 0.16 µg/mL, respectively, as compared with the non-nano particle formulation with an IC50 of 8.47 ± 0.29 µg/mL. These findings suggest that CSNPs can enhance the physicochemical characteristics and cytotoxicity of AMG in breast cancer treatment.

Intranasal delivery of chitosan decorated nanostructured lipid carriers of Buspirone for brain targeting: Formulation development, optimization and In-Vivo preclinical evaluation

The current research was portrayed to design and optimize the Chitosan (CH) coated Buspirone-loaded nanostructured lipid carriers (BPE-CH-NLCs) for nose to brain delivery. NLCs were developed by solvent diffusion evaporation technique, coated with CH, and then optimized to the maximum efficiency using the quality by design (QbD) based Box-Behnken design (BBD). Glyceryl monostearate (GMS) & oleic acid mixture and tween 80 were used as a lipid and surfactant, respectively. The prepared NLCs were subjected to in-vitro characterization. In-vivo pharmacokinetic and neuro-pharmacokinetic (drug targeting efficiency-DTE, direct transport percentage-DTP) parameters were evaluated on Wister rats. The results revealed that the optimized formulation exhibited acceptable PS (190.98 ± 4.72 nm), ZP (+17.47 mV), and EE (80.53 ± 1.26% w/w), and the TEM image showed that the drug was incorporated adequately in NLCs. DSC findings exposed that the drug was present in amorphous form within the NLCs. The optimized formulation exhibited 27.61 months shelf life and was found to be stable under studied conditions. The value of AUC (bioavailability) for BPE-CH-NLCs administered i.n was found to be 3.06 folds compared to BPE-CH-NLCs administered i.v, and 2.17 folds compared to BPE-Sol administered i.n. A higher value of DTE (1462.49%) for developed NLCs confirmed the brain targeting efficiency of these lipid nanoparticles. DTP value for BPE-CH-NLCs (93.16%) was significantly (p < 0.05) higher than BPE-Sol (81.63%), indicating the efficient targeting potential of lipid nanoparticles compared to drug solutions. Finally, it could be possible to infer that GMS-Oleic acid-based NLCs coated with CH might be effective carriers to administer BPE to the brain via the nasal route.

Trends of Chitosan Based Delivery Systems in Neuroregeneration and Functional Recovery in Spinal Cord Injuries

Spinal cord injury (SCI) is one of the most complicated nervous system injuries with challenging treatment and recovery. Regenerative biomaterials such as chitosan are being reported for their wide use in filling the cavities, deliver curative drugs, and also provide adsorption sites for transplanted stem cells. Biomaterial scaffolds utilizing chitosan have shown certain therapeutic effects on spinal cord injury repair with some limitations. Chitosan-based delivery in stem cell transplantation is another strategy that has shown decent success. Stem cells can be directed to differentiate into neurons or glia in vitro. Stem cell-based therapy, biopolymer chitosan delivery strategies, and scaffold-based therapeutic strategies have been advancing as a combinatorial approach for spinal cord injury repair. In this review, we summarize the recent progress in the treatment strategies of SCI due to the use of bioactivity of chitosan-based drug delivery systems. An emphasis on the role of chitosan in neural regeneration has also been highlighted.

Intranasal delivery of chitosan decorated PLGA core /shell nanoparticles containing flavonoid to reduce oxidative stress in the treatment of Alzheimer's disease

Curcumin (Cur), an antioxidant flavonoid has demonstrated high efficiency in attenuating oxidative stress in Alzheimer's disease (AD). Nevertheless, despite of its therapeutic potential, its clinical applications are hindered due to low solubility and low bioavailability and and first-pass metabolism. Thus, we fabricated Cur encapsulated chitosan functionalized PLGA core/shell NPs (CH@Cur-PLGA C/S NPs) and administered via intranasal route. Research also include comparative study of PLGA NPs (core) and CH@Cur-PLGA C/S NPs (C/S NPs) to investigate effect of CH coating over PLGA NPs on therapeutic efficacy, cellular uptake and stability. Fabricated NPs were extensively characterized and confirmed Cur encapsulation with 75% of entrapment efficiency and particle size in the range of 200 nm. TEM analysis confirmed uniform coating of CH over PLGA NPs. Release and permeation study demonstrated sustained release and enhanced permeation through nasal mucosa. Cellular uptake mechanism showed caveolae-mediated-enhance endocytosis of NPs. In-vitro BBB-co-cufure model exhibited efficient passage for C/SNPs. Antioxidant assay demonstrated significant ROS scavenging activity of C/SNPs. In-vivo toxicity showed insignificant toxicity. Bio-distribution of C/S NPs was higher in brain following intranasal route. Photo and thermal stability confirmed protection of Cur by C/SNPs. Obtained results demonstrate potential application of C/SNPs for reducing oxidative stress in brain for effective AD treat.

Antidiabetic effects and safety profile of chitosan delivery systems loaded with new xanthine-thiazolidine-4-one derivatives: in vivo studies

Based on important biological effects associated with xanthine and thiazolidine-4-one moieties, especially hypoglycemic and antioxidant, new xanthine derivatives with thiazolidine-4-one scaffold (XTDs, 6a-k) have been synthesized and reported by our research group, as new potential multitarget antidiabetic drugs. The goal of this work was to evaluate the in vivo antidiabetic potential and safety profile of the most proper XTDs (6c, 6e) and their chitosan based formulations, CS-XTDs (CS-6c, CS-6e) selected based on previous results in terms of their in vitro antioxidant effects and physic-chemical characteristics. Using a streptozotocin-induced diabetes model, the hypoglycemic effect (postprandial glycemia and glycated hemoglobin), biochemical markers of liver and kidney function, as well as hematological markers have been evaluated. The effect on lipid profile and clinical parameters (body weight, food, and water intake) has been also monitored. Moreover, the biopharmaceutical characteristics of 6c and 6e were predicted using in silico computerized methods. The treatment of diabetic rats with CS-XTDs, especially CS-6c was associated with appreciable hypoglycemic effect, the values of postprandial glycemia and glycated hemoglobin being similar with pioglitazone, used as reference drug. In addition, the recorded values for liver enzymes (AST, ALT, LDH), bilirubin (direct, total) and kidney biochemical markers (creatinine, uric acid, urea) were also comparable with pioglitazone. Also, CS-6c was associated with good hematological markers and clinical parameters. The results highlighted the efficiency of the developed chitosan delivery system CS-6c for the treatment of diabetes mellitus syndrome, acting as a potential multitarget agent.

Hydrogel Delivery System Containing Calendulae flos Lyophilized Extract with Chitosan as a Supporting Strategy for Wound Healing Applications.

Calendulae flos is a valued plant material with known anti-inflammatory and antimicrobiological properties. The limitation for its use in the treatment of chronic wounds is the lack of adhesion to the required site of action. Obtaining the Calendulae flos lyophilized extract from water-ethanolic extract allowed to prepare valuable material whose biological activity in the wound healing process was confirmed by a positive result of the scratch test. The Calendulae flos lyophilized extract was standardized for the contents of the chlorogenic acid and the narcissin. The significant potency of the Calendulae flos pharmacological activity has become the reason for studies on its novel applications in combination with the multifunctional chitosan carrier, to create a new, valuable solution in the treatment of chronic wounds. The use of chitosan as a carrier allowed for the controlled release of the chlorogenic acid and the narcissin. These substances, characterized by prolonged release from the chitosan delivery system, were identified as well permeable, based on the results of the studies of the parallel artificial membrane permeability assay (PAMPA Skin) a model simulating permeability through membrane skin. The combination of the Calendulae flos lyophilized extract and the chitosan allowed for synergy of action towards hyaluronidase inhibition and effective microbiological activity. Optimization of the hypromellose hydrogel preparation ensuring the required rheological properties necessary for the release of the chlorogenic acid and the narcissin from the chitosan delivery system, as well as demonstrated antimicrobial activity allows indicating formulations of 3% Calendulae flos lyophilized extract with chitosan 80/500 in weight ratio 1:1 and 2% or 3% hypromellose as an important support with high compliance of response and effectiveness for patients suffering from chronic wounds.

Mucoadhesive Chitosan Delivery System with Chelidonii Herba Lyophilized Extract as a Promising Strategy for Vaginitis Treatment.

Chelidonium majus (also known as celandine) contains pharmacologically active compounds such as isoquinoline alkaloids (e.g., chelidonine, sanguinarine), flavonoids, saponins, carotenoids, and organic acids. Due to the presence of isoquinoline alkaloids, Chelidonii herba extracts are widely used as an antibacterial, antifungal, antiviral (including HSV-1 and HIV-1), and anti-inflammatory agent in the treatment of various diseases, while chitosan is a biocompatible and biodegradable carrier with valuable properties for mucoadhesive formulations preparation. Our work aimed to prepare mucoadhesive vaginal drug delivery systems composed of Chelidonii herba lyophilized extract and chitosan as an effective way to treat vaginitis. The pharmacological safety of usage of isoquinoline alkaloids, based on MTT test, were evaluated for the maximum doses 36.34 ± 0.29 µg/mL and 0.89 ± 1.16 µg/mL for chelidonine and sanguinarine, respectively. Dissolution rate profiles and permeability through artificial membranes for chelidonine and sanguinarine after their introduction into the chitosan system were studied. The low permeability for used save doses of isoquinoline alkaloids and results of microbiological studies allow confirmation that system Chelidonii herba lyophilized extract chitosan 80/500 1:1 (w/w) is a promising strategy for vaginal use. Ex vivo studies of mucoadhesive properties and evaluation of tableting features demonstrated that the formulation containing Chelidonii herba lyophilized extract (120.0 mg) with chitosan (80/500—100.0 mg) and polymer content (HPMC—100.0 mg, microcrystalline cellulose—50.0 mg, lactose monohydrate—30.0 mg and magnesium stearate—4.0 mg) is a vaginal dosage form with prolonging dissolution profile and high mucoadhesion properties (up to 4 h).

Antibiofilm and mucolytic action of nitric oxide delivered via gas or macromolecular donor using in vitro and ex vivo models

The combination of antibacterial and mucolytic actions makes nitric oxide (NO) an attractive dual-action cystic fibrosis (CF) therapeutic. The delivery of any therapeutic agent through pathological mucus is difficult, and the use of inhaled NO gas is inherently limited by toxicity concerns. Herein, we directly compare the ability of NO to eradicate infection and decrease mucus viscoelastic moduli as a function of delivery method (i.e., as a gas or water-soluble chitosan donor). To compare bactericidal action in tissue, an ex vivo porcine lung model was infected and treated with either gaseous NO or NO-releasing chitosan for 5h. In vitro Pseudomonas aeruginosa biofilm viability was quantified after NO treatment. Human bronchial epithelial mucus and CF sputum were exposed to NO and their viscoelastic moduli measured with parallel plate macrorheology. Larger NO concentrations were achieved in solution when delivered by chitosan relative to gas exposure. The bactericidal action in tissue of the NO-releasing chitosan was greater compared to NO gas in the infected tissue model. Chitosan delivery also resulted in improved antibiofilm action and reduced biofilm viability (2-log) while gaseous delivery had no impact at an equivalent dose (~0.8µmol/mL). At equivalent NO doses, mucus and sputum rheology were significantly reduced after treatment with NO-releasing chitosan with NO gas having no significant effect. Delivery of NO by chitosan allows for larger in-solution concentrations than achievable via direct gas with superior bactericidal and mucolytic action.

Combination of Rhamnolipid and Chitosan in Nanoparticles Boosts Their Antimicrobial Efficacy.

Nanomaterials have emerged as antimicrobial agents due to their unique physical and chemical properties. The development of nanoparticles (NPs) composed of natural biopolymers and biosurfactants have sparked interest, as they can be obtained without the use of complex chemical synthesis and toxic materials. In this study, we develop antimicrobial nanoparticles combining the biopolymer chitosan with the biosurfactant rhamnolipid. Addition of rhamnolipid reduced the size and polydispersity index of chitosan nanoparticles showing a more positive surface charge with improved stability, suggesting that chitosan-free amino groups are predominantly present on the surface of nanoparticles. Antimicrobial activity of chitosan/rhamnolipid nanoparticles (C/RL-NPs) against Staphylococcus strains surpassed that of either single rhamnolipid or chitosan, both in planktonic bacteria and biofilms. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of C/RL-NPs were determined considering the concentration of each individual molecule in NPs. MIC values of 14/19 μg mL-1 and MBC of 29/37 μg mL-1 were observed for S. aureus DSM 1104 and MIC and MBC of 29/37 and 58/75 μg mL-1 were observed against S. aureus ATCC 29213, respectively. For S. epidermidis, MIC and MBC of 7/9 and 14/19 μg mL-1 were noticed. Chitosan and chitosan nanoparticles eliminate the bacteria present in the upper parts of biofilms, while C/RL-NPs were more effective, eradicating most sessile bacteria and reducing the number of viable cells below the detection limit, when NPs concentration of 58/75 μg mL-1 was applied for both S. aureus DSM 1104 and S. epidermidis biofilms. The improved antibacterial efficacy of C/RL-NPs was linked to the increased local delivery of chitosan and rhamnolipid at the cell surface and, consequently, to their targets in Gram-positive bacteria. The combination of chitosan and rhamnolipid offers a promising strategy to the design of novel nanoparticles with low cytotoxicity, which can be exploited in pharmaceutical and food industries.

Effects of three drying methods on the physical properties and drug delivery in chitosan microspheres

The purpose of this study is to investigate the effects of different drying methods on the physical properties and drug delivery of chitosan microspheres. Three types of drying methods were utilized, including air drying and freeze drying after freezing at -20 ℃ (slow cooling) and at -80 ℃ (fast cooling). The physical properties of microspheres were characterized. Utilizing bovine serum albumin (BSA) as the model drug, the in-vitro release behaviors of drug-loaded beads were investigated. By comparing the physical properties of the different drying methods, the microspheres' diameters, porosities, and surface area were observed to increase successively from air drying and slow cooling to fast cooling, whereas the pore size and the swelling and degradation rates varied. The drug-loading experiments revealed that the loading capacity of air-dried microspheres was the lowest and the release rate was the slowest. Although the loading capacity of fast cooling microspheres was high, an obvious burst release was observed. The loading capacity of slow cooling microspheres was similar to that of the fast cooling microspheres and the loaded BSA can be released continuously. The results indicate that different drying methods can affect the physical properties of chitosan microspheres, which further influence drug loading and release.

Systemic Delivery of Free Chitosan Accelerates Femur Fracture Healing in Rats.

Chitosan-containing compounds have been shown to be suitable for bone replacement, but few studies demonstrate the impact of the chitosan as a free drug on the fracture.In this study, we aimed to evaluate possible effects of free chitosan on fracture healing. Thirty adult male Sprague-Dawley rats with a mean body weight of 205 g (range from 200g to 210g) were randomly and equally divided into two groups. Standardized femur fractures were created in all rats. Treatments were administered intraperitoneally twice weekly at 1 mg chitosan per injection and the controls were administered physiological saline. The site of the fracture was compared with the control group at 1, 2 and 4 weeks after surgery (n=5 in each group). The weight, activity and reaction of the rats were observed at all the timepoints. Anterior-posterior radiographs and micro-CT scans of all fractures were taken after surgery, and the parameters included: the volume of callus that was calculated using the Perkins volume formula, BV/TV, BV, BMD of cortical bone, cortical thickness, and cortical number at the fracture sites. After sacrifice, fractured femurs from rats were dissected and carefully cleaned of muscle around the fracture callus to preserve callus integrity. Sections were stained with haematoxylin and eosin for histological evaluation of healing. Radiological (X-ray and micro-CT) evaluation showed that fracture healing of the experimental group was better than control group at the second week and fourth week. Histological evaluation revealed fracture healing of the experimental group was better than control group at the same time. There was no statistically significant difference in fracture healing between the two groups at the first week. Systemic delivery of free chitosan can accelerate the bone healing process in rat femur fracture at the early-middle stage.

Targeted gene delivery of polyethyleneimine-grafted chitosan with RGD dendrimer peptide in αvβ3 integrin-overexpressing tumor cells

The safe and effective delivery of genetic material into cells is a necessary factor for gene therapy. Although a wide range of materials, methods, and combinations have been reported, successful gene therapy has been limited. In the present study, a targeted gene carrier for αvβ3 integrin-overexpressing tumor cells was designed using widely applied materials containing water soluble chitosan (WSC), RGD peptide, and polyethyleneimine (PEI). The physiological characteristics, in vitro targeted gene transfection, cytotoxicity, blood-compatibility, and cellular distributions were investigated. In particular, a study of the endocytic mechanism revealed processes of microtubule-dependent macropinocytosis and clathrin-mediated endocytosis. Furthermore, the PEI/WSC copolymer with a dendrimer RGD peptide (four-branched RGD moiety) as a targeting moiety suppressed the growth of a solid tumor mass in vivo mouse xenograft model generated with PC3 prostate tumor cells by silencing BCL2 mRNA. This result indicated RGD/PEI/WSC copolymer for a good candidate as a simple and biocompatible gene carrier.

Effective attenuation of vascular restenosis following local delivery of chitosan decorated sirolimus liposomes

Assuring the efficient local delivery via biocompatible nanosystems can be considered as a promising therapy for restenosis. The aim of the present study was preparation, in vitro characterization, and in vivo efficacy evaluation of sirolimus containing chitosan decorated liposomes for restenosis treatment. Liposomes were coated with chitosan, leading to ∼38nm increase in the particle size and a positive shift in the zeta potential from −1mV to +21mV. Chitosan modification was also confirmed by TEM, increased stability against detergent solubilization, and FTIR analyses. High entrapment efficiency (≥83%) and sustained release behaviors were demonstrated in both coated and uncoated vesicles. Compared to control groups, treatment of balloon injured rats with uncoated and chitosan-coated liposomes (50μg sirolimus) significantly reduced stenosis by 39% and 62%, respectively. The effect was also confirmed by immunohistochemical and in vivo CT angiography imaging studies. Chitosan-coated liposomes could be a novel platform for restenosis treatment.