Correction to: Evaluation of Wound Healing Potential of ß-Chitin Hydrogel/Nano Zinc Oxide Composite Bandage.

In the original manuscript, the platelet activation images of the sample treated groups, Fig. 3c were provided incorrectly.

Evaluation of wound healing potential of ß-chitin hydrogel/nano zinc oxide composite bandage.

PURPOSE: ß-chitin hydrogel/nZnO composite bandage was fabricated and evaluated in detail as an alternative to existing bandages. METHODS: ß-chitin hydrogel was synthesized by dissolving ß-chitin powder in Methanol/CaCl(2) solvent, followed by the addition of distilled water. ZnO nanoparticles were added to the ß-chitin hydrogel and stirred for homogenized distribution. The resultant slurry was frozen at 0°C for 12 h. The frozen samples were lyophilized for 24 h to obtain porous composite bandages. RESULTS: The bandages showed controlled swelling and degradation. The composite bandages showed blood clotting ability as well as platelet activation, which was higher when compared to the control. The antibacterial activity of the bandages were proven against Staphylococcus aureus (S. aureus) and Escherichia coli (E.coli). Cytocompatibility of the composite bandages were assessed using human dermal fibroblast cells (HDF) and these cells on the composite bandages were viable similar to the Kaltostat control bandages and bare ß-chitin hydrogel based bandages. The viability was reduced to 50-60% in bandages with higher concentration of zinc oxide nanoparticles (nZnO) and showed 80-90% viability with lower concentration of nZnO. In vivo evaluation in Sprague Dawley rats (S.D. rats) showed faster healing and higher collagen deposition ability of composite bandages when compared to the control. CONCLUSIONS: The prepared bandages can be used on various types of infected wounds with large volume of exudates.

Injectable Pectin-Alginate Hydrogels for Improving Vascularization and Adipogenesis of Human Fat Graft.

Autologous fat grafting (AFG) is the most prevailing tool for soft tissue regeneration in clinics, although efficiency is limited to unpredictable volume resorption due to poor vascularization and eventual necrosis. This study sought to improve the AFG efficiency using a hydrogel as a carrier for human fat graft (F) with and without platelet-rich plasma (PRP). PRP is clinically well known for the local release of several endogenous growth factors and has been in clinical use already. A human-fat-graft-encapsulated pectin-alginate hydrogel (FG) was developed and characterized. PRP was added to F to develop a human fat graft with PRP (FP). FP was admixed with a pectin-alginate hydrogel to develop FGP. FG and FGP showed the smooth injectable, elastic, and shear-thinning properties. FG and FGP groups showed enhanced cell viability and proliferation compared to the control F in vitro. We also investigated the in vivo angiogenesis and neo-adipogenesis ability of F, FG, FGP, and FP in nude mice after subcutaneous injection. After 2 and 4 weeks, an MRI of the mice was conducted, followed by graft explantation. The explanted grafts were also assessed histologically and with immunohistochemistry (IHC) studies. MRI and histology results revealed better vascularity of the FG and FGP system compared to fat graft alone. Further, the IHC studies, CD 31, and perilipin staining also revealed better vasculature and adipogenesis of FG and FGP systems. These results indicate the enhanced angiogenesis and adipogenesis of FG and FGP. Thus, developed pectin-alginate hydrogel-based fat graft systems FG and FGP replenish the native microenvironment by mediating angiogenesis and adipogenesis, thereby maximizing the clinical outcomes of autologous fat grafting.

Role of FGF-18 in Bone Regeneration.

In tissue engineering, three key components are cells, biological/mechanical cues, and scaffolds. Biological cues are normally proteins such as growth factors and their derivatives, bioactive molecules, and the regulators of a gene. Numerous growth factors such as VEGF, FGF, and TGF-ß are being studied and applied in different studies. The carriers used to release these growth factors also play an important role in their functioning. From the early part of the 1990s, more research has beenconductedon the role of fibroblast growth factors on the various physiological functions in our body. The fibroblast growth factor family contains 22 members. Fibroblast growth factors such as 2, 9, and 18 are mainly associated with the differentiation of osteoblasts and in bone regeneration. FGF-18 stimulates the PI3K/ERK pathway and smad1/5/8 pathway mediated via BMP-2 by blocking its antagonist, which is essential for bone formation. FGF-18 incorporated hydrogel and scaffolds had showed enhanced bone regeneration. This review highlights these functions and current trends using this growth factor and potential outcomes in the field of bone regeneration.

Nano-based formulations of curcumin: elucidating the potential benefits and future prospects in skin cancer.

Skin cancer refers to any malignant lesions that occur in the skin and are observed predominantly in populations of European descent. Conventional treatment modalities such as excision biopsy, chemotherapy, radiotherapy, immunotherapy, electrodesiccation, and photodynamic therapy (PDT) induce several unintended side effects which affect a patient's quality of life and physical well-being. Therefore, spice-derived nutraceuticals like curcumin, which are well tolerated, less expensive, and relatively safe, have been considered a promising agent for skin cancer treatment. Curcumin, a chemical constituent extracted from the Indian spice, turmeric, and its analogues has been used in various mammalian cancers including skin cancer. Curcumin has anti-neoplastic activity by triggering the process of apoptosis and preventing the multiplication and infiltration of the cancer cells by inhibiting some signaling pathways and thus subsequently preventing the process of carcinogenesis. Curcumin is also a photosensitizer and has been used in PDT. The major limitations associated with curcumin are poor bioavailability, instability, limited permeation into the skin, and lack of solubility in water. This will constrain the use of curcumin in clinical settings. Hence, developing a proper formulation that can ideally release curcumin to its targeted site is important. So, several nanoformulations based on curcumin have been established such as nanogels, nanoemulsions, nanofibers, nanopatterned films, nanoliposomes and nanoniosomes, nanodisks, and cyclodextrins. The present review mainly focuses on curcumin and its analogues as therapeutic agents for treating different types of skin cancers. The significance of using various nanoformulations as well non-nanoformulations loaded with curcumin as an effective treatment modality for skin cancer is also emphasized.

Antiseptic Chitosan-Poly(hexamethylene) Biguanide Hydrogel for the Treatment of Infectious Wounds.

Topical wound infections create the ideal conditions for microbial colonization and growth in terms of moisture, temperature, and nutrients. When they are not protected, numerous types of bacteria from the internal microbiota and the external environment may colonize them, creating a polymicrobial population. Treatment of these wounds often necessitates the use of antibiotics that may have systemic harmful effects. Unlike antibiotics, topical antiseptics exhibit a wider range of activity and reduced systemic toxicity and resistance. In order to address this issue, we developed an antiseptic Chitosan-Poly (hexamethylene) Biguanide (CS-PHMB) hydrogel. The prepared hydrogel was characterized using Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). SEM images showed the smooth morphology and characteristic FTIR peaks of PHMB and confirmed the incorporation of the antiseptic into the chitosan (CS) hydrogel. A Water Vapor Permeation Rate study confirms the moisture retention ability of the CS-PHMB hydrogel. Rheological studies proved the gel strength and temperature stability. The prepared hydrogel inhibited the growth of S. aureus, P. aeruginosa, E. coli, methicillin-resistant Staphylococcus aureus (MRSA), and K. pneumoniae, which confirms its antibacterial properties. It also inhibited biofilm formation for S. aureus and E. coli. CS-PHMB hydrogel is also found to be hemo- and cytocompatible in nature. Thus, the developed CS-PHMB hydrogel is a very potent candidate to be used for treating infectious topical wounds with low systemic toxicity.

Chitin scaffolds in tissue engineering.

Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine.

Prospection of chitosan and its derivatives in wound healing: Proof of patent analysis (2010-2020).

Disruption in the normal anatomy and physiology of the skin often leads to wound formation. Its healing is a pretty complex and dynamic biological process with different phases. While there are many biopolymers (and their derivatives) for wound healing purposes. One of the most popular, promising, progressive and attention-grabbing biopolymers is 'chitosan'. It is a polysaccharide biopolymer that has tremendous potential in augmenting the process of wound healing. Most importantly, the derivatives of chitosan have heavily attracted the scientific community's attention to employing them in various formulations for wound healing applications. The prime focus of the present review is to provide scientific and technological prospection about chitosan and its derivatives for wound healing activity, starting from 2010 to 2020. Besides, the review also focuses about toxicity, different formulations and products of chitosan that are currently under clinical trials for wound healing purposes are described. Through this review, we present evidence that abundantly confirms that there is a growing interest in the domain of wound healing using novel, inventive, useful and patent protected chitosan derivatives. We speculate the possibility of more patent protected chitosan derivatives in the future for wound healing applications.

Combinatorial effect of nano whitlockite/nano bioglass with FGF-18 in an injectable hydrogel for craniofacial bone regeneration.

Functional regeneration of bone defects, especially critical-sized, in the craniofacial region remains a major clinical challenge that needs intervention. To address this, the present work focuses on the development of an injectable chitin-PLGA hydrogel (CG) containing bioglass nanoparticles (nBG) or whitlockite nanoparticles (nWH) with FGF-18, and compares the osteogenic and neo-bone formation potential against commercially available hydroxyapatite nanoparticles (nHAP) with FGF-18 fortified CG hydrogel in the critical-sized defect region. The developed CG was injectable and the incorporation of bio-ceramics didn't affect the injectability. Sustained release of FGF-18 was achieved in bio-ceramic containing CG hydrogel systems, while CG hydrogel alone displayed rapid release. In addition, the nBG or nWH containing CG hydrogel groups showed in vitro angiogenic potential. Furthermore, ALP activity, BMP-2 quantification and osteogenic gene expression assays were conducted to ascertain the osteogenic differentiation potential of the hydrogels. In the combination groups, CGnWHF (nWH + FGF-18 containing CG) showed highest osteogenic potential with a synergistic effect, compared to all other groups studied. In vivo bone regeneration studies displayed near-complete bone regeneration for CGnWHF, where its BV/TV% was the highest (synergistic effect) compared to CGnBGF (nBG + FGF-18 in CG) and nHAP with FGF-18 (additive effect) after 8 weeks of implantation. Thus, the use of CGnWHF in irregular craniofacial bone defects could be an attractive option.

Nano polydopamine crosslinked thiol-functionalized hyaluronic acid hydrogel for angiogenic drug delivery.

Crosslinking of polymeric network using nanoparticles by physical or chemical method to obtain hydrogel is an emerging approach. Herein, we synthesized Polydopamine (PDA) nanoparticles via oxidative self-polymerization of dopamine in water-ethanol mixture. Thiol-functionalized hyaluronic acid was developed using cysteamine and hyaluronic acid (HA-Cys) via 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodiimide - N-hydroxysuccinimide (EDC-NHS) crosslinking chemistry. Developed HA-Cys conjugate was cross-linked using PDA nanoparticles via Michael-type addition reaction. Synthesized nanoparticles were monodisperse with size of 124 ± 8 nm and had spherical morphology. FTIR characterization confirmed successful synthesis of HA-Cys conjugate and subsequent crosslinking with PDA nanoparticles. Rheological characterization revealed that hydrogels were injectable in nature with good mechanical stability. Dimethyloxalylglycine (DMOG) loaded PDA nanoparticle showed sustained drug release for period of 7 days from composite hydrogel. Hydrogel microenvironment facilitated enhanced endothelial cell migration, proliferation and attachment. Furthermore, in response to release of DMOG from developed hydrogel, cells showed enhanced capillary tube formation in vitro. Overall, these results demonstrate that PDA cross-linked thiol-functionalized hydrogel was developed in a facile manner under physiological conditions. These developed hydrogels could be potentially used in tissue engineering and drug delivery.

Injectable chitosan-nano bioglass composite hemostatic hydrogel for effective bleeding control.

Effective bleeding control is a major concern in trauma and major surgeries. Chitosan (Ch) as hemostatic agent has been widely used and when applied at the site of injury it acts by aggregating blood cells and forming a plug. Our prime interest is to improve the blood clotting property of Ch hydrogel. Incorporation of nanobioglass (nBG) with silica (activate coagulation factor XII), calcium (activate intrinsic pathway) and phosphate (initiates extrinsic pathway) ions into Ch hydrogel (protonated NH2 group) would act at the same time and bring about rapid blood clot formation. Sol-gel method was followed to synthesize nBG particles and its particle size was found to be 14 ±â€¯3 nm. 2%Ch-5%nBG hydrogel was then prepared and studied using SEM and FTIR. The prepared hydrogel was injecable and was also cytocompatible with HUVEC. In in vitro blood clotting study and in vivo major organ injury model, 2%Ch-5%nBG hydrogel formed rapid blood clot than 2%Ch hydrogel. Hence, 2%Ch-5%nBG hydrogel might have great potential to achieve effective bleeding control during critical situations.

Erratum: Fabrication of Chitin/Poly(butylene succinate)/Chondroitin Sulfate Nanoparticles Ternary Composite Hydrogel Scaffold for Skin Tissue Engineering. Polymers, 2014, 6, 2974⁻2984.

The authors wish to make a change to the published paper [...].

Injectable Nano Whitlockite Incorporated Chitosan Hydrogel for Effective Hemostasis.

Uncontrolled bleeding can lead to many complications that might cause multiple organ failures and even death. Of all the hemostatic agents used, chitosan has been reported to show better hemostatic potential. It acts through one mechanism involved in hemostasis that is plug formation by adhering to the injured site. Hence our focus is to enhance the hemostatic potential of chitosan (Ch) hydrogel by incorporating nano whitlockite (nWH: Ca18Mg2(HPO4)2(PO4)12) that would release Ca2+, Mg2+, and PO43- ions that would simultaneously initiate the coagulation cascade. Ch-nWH composite hydrogel can act simultaneously on different mechanisms involved in hemostasis and bring about rapid bleeding control. The nWH particles were synthesized using precipitation technique and were characterized. Particle size of nWH was found to be 75 ± 5 nm. Composite hydrogel was characterized using FTIR and XRD to confirm the presence of different constituents of the hydrogel. Rheological studies showed the shear-thinning property and increased elastic modulus of the composite hydrogel compared to Ch hydrogel. 2%Ch-4%nWH hydrogel was observed to be cytocompatible with Human Umbilical Vein Endothelial Cells (HUVEC). In the in vitro blood clotting analysis using citrated human whole blood, 2%Ch-4%nWH hydrogel showed rapid blood clot formation compared to control 2%Ch hydrogel. Further in vivo experiments performed on liver and femoral artery injuries created on Sprague-Dawley (S.D) rat model reveals that 2%Ch-4%nWH hydrogel promoted rapid bleeding control and less volume of blood loss compared to Ch hydrogel. These in vitro and in vivo results showed that incorporation of nWH has enhanced the hemostatic potential of Ch hydrogel. Therefore, the synthesized 2%Ch-4%nWH hydrogel may be a promising system that could bring about rapid hemostasis during life threatening bleeding.

Ciprofloxacin- and Fluconazole-Containing Fibrin-Nanoparticle-Incorporated Chitosan Bandages for the Treatment of Polymicrobial Wound Infections.

Polymicrobial wound infections often require high dosages of antibiotics and fungicides. However, prolonged antimicrobial therapies are associated with potential systemic side effects and an increased risk of the development of drug-resistant microbes. With this focus, we aimed at developing chitosan bandages loaded with antimicrobial drug (ciprofloxacin and fluconazole) nanoparticles for a sustained slow release of drugs. The particle sizes of the prepared ciprofloxacin- and flucanazole-loaded fibrin nanoparticles were observed to be 132 ± 16 and 175 ± 17 nm, respectively. The chitosan bandages with drug-containing nanoparticles were flexible and had adequate tensile strength and porosity of 80-85%, which would favor excess exudate absorption in an infectious wound. The in vitro toxicity of the bandages studied against the human dermal fibroblast cell line proved its cytocompatibility. Ciprofloxacin and fluconazole were released from bandages for up to 14 days in a sustained manner. The antimicrobial-drug-loaded bandages showed significant antimicrobial activity toward polymicrobial cultures of Candida albicans, Escherichia coli, and Staphylococcus aureus in vitro and ex vivo. In vivo studies were conducted on a polymicrobially infected rat wound model. A significant reduction in microbial load was obtained upon application of antimicrobial-drug-loaded chitosan bandages in vivo.

Antistaphylococcal and Neutrophil Chemotactic Injectable κ-Carrageenan Hydrogel for Infectious Wound Healing.

Staphylococcus aureus wound infection is a major concern due to the resistance of S. aureus to topical antibiotics and capacity to inhibit neutrophil migration at the infection site. To overcome these problems, we have developed 0.01% (v/v) octenidine dihydrochloride (Oct) and 0.5% (w/w) chitosan-treated serum (CTS) containing 1.5% (w/v) κ-carrageenan hydrogel (κC). Oct is an antiseptic agent, against which no resistance is reported so far, and CTS has neutrophilic attractant properties. The prepared Oct-CTS-κC hydrogel is injectable and biocompatible. Using in vitro experiments, we demonstrated CTS can induce the migration of polymorphonuclear neutrophils (PMNs) and fibroblasts that can facilitate tissue regeneration at a wound site. In vitro release studies revealed a sustained release of Oct and serum proteins from the Oct-CTS-κC hydrogel. Antibacterial properties of developed hydrogels were tested against S. aureus and its clinical isolates. Further, the in vivo antibacterial efficacy of the prepared hydrogel was evaluated in an S. aureus-infected Sprague-Dawley (SD) rat wound. Both in vitro and in vivo studies showed that the Oct-CTS-κC hydrogel inhibited S. aureus growth. Thus, the developed Oct-CTS-κC hydrogel can be potentially exploited for S. aureus-infected wound healing.

Bioengineered Braided Micro-Nano (Multiscale) Fibrous Scaffolds for Tendon Reconstruction.

A braided multiscale fibrous scaffold consisting of aligned PCL micro/collagen-bFGFnano fibers was fabricated (mPCL-nCol-bFGF) to mimic native tendon tissue architecture which was further coated with alginate to aid in prevention of peritendinous adhesion. The bFGF release kinetics showed a sustained release of growth factors for a period of 20 days. Further, in vitro cell viability, attachment, and proliferation were performed using rabbit tenocytes under static and dynamic conditions. mPCL-nCol-bFGF showed a higher cell proliferation and enhanced expression of tenogenic markers compared to mPCL-nCol (braided scaffold without bFGF). When subjected to dynamic stimulation in a bioreactor, mPCL-nCol-bFGF-DS (braided scaffold with bFGF after dynamic stimulation) showed enhanced cellular proliferation and tenogenic marker expression, compared to mPCL-nCol-bFGF. The in vivo studies of the cell seeded scaffold after dynamic stimulation in Achilles tendon defect model showed tendon tissue regeneration with aligned collagen morphology within 12 weeks of implantation.

Injectable in Situ Shape-Forming Osteogenic Nanocomposite Hydrogel for Regenerating Irregular Bone Defects.

The in situ forming injectable hydrogels are appealing for irregular bone defects because of the ease of administration and the addition of ceramics, molecules, and proteins into the hydrogel. We have developed in situ shape-forming hydrogel using oxidized alginate and gelatin as the hydrogel matrix. Whitlockite bioceramic nanoparticles (WH NPs) were incorporated, as they provide enhanced osteogenic stimulation compared to hydroxyapatite via providing higher local ion concentration. The drug simvastatin was also incorporated into the hydrogel system, as it increases the expression of BMP-2 thereby provide environment for bone regeneration. The presence of both WH nanoparticles and simvastatin would enhance bone regeneration potential. The whitlockite nanoparticles (80 ± 8 nm) were synthesized by precipitation method and were characterized. The nanocomposite hydrogel system was characterized by SEM, FTIR and rheologically. The gelation time of the in situ nanocomposite hydrogel was determined by rheological analysis as 28 s, whereas hydrogel alone showed 132 s. Addition of WH NPs not only shortened the gelation time but also increased the gel strength. The in vitro release of simvastatin from the nanocomposite hydrogel showed a release over a period of 28 days. The alkaline phosphatase (ALP) level also showed a significant increase. RUNX2 and BMP2 expressions showed that nanocomposite hydrogel enhanced the osteogenic differentiation. In vivo bone regeneration studies in mice cranial defect studies showed nanocomposite hydrogel was effective in regenerating the bone compared to controls. Thus, the simvastatin-incorporated oxidized alginate-gelatin/WH NPs hydrogel system has the potential to be used as a repairing and regenerative system in cranial bone defects.

Pro-angiogenic Molecules for Therapeutic Angiogenesis.

BACKGROUND: Therapeutic angiogenesis is a clinical intervention for controlled stimulation and augmentation of neovascularisation in ischemic tissues. Conventional therapeutic techniques involve proangiogenic factor based induction of host tissue angiogenesis. In this review, we provide a holistic idea about therapeutic angiogenesis while specifically highlighting the role of proangiogenic factors as growth factors, peptides, small molecules and polysaccharides in tissue neovascularisation. METHODS: A detailed search of peer-reviewed literature was carried out with prime focus on therapeutic angiogenesis and proangiogenic factors. The content of each literature reviewed in this paper was qualitatively analysed for particulars and relevance to the subject of study. This work has been distributed under four broad titles, namely, proangiogenic growth factors, peptides, small molecules and polysaccharides. Also, recent developments pertaining to proangiogenic factors for therapeutic angiogenesis have been detailed. RESULTS: A total of 244 literatures have been reviewed from the bibliographic database to present a conceptual understanding about the importance of proangiogenic factors in revascularisation of ischemic tissues. CONCLUSION: This review focuses on importance of various proangiogenic factors, with reference to therapeutic angiogenesis. Thorough analysis of clinical data reveals the dearth of a defined system for proangiogenic growth factor delivery. Designing of a biomaterial based paradigm for growth factor therapy, might help in enhancing clinical translation of therapeutic angiogenesis.

In vivo evaluation of cetuximab-conjugated poly(γ-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts.

Epidermal growth factor receptor (EGFR), upregulated in gastric cancer patients, is an oncogene of interest in the development of targeted cancer nanomedicines. This study demonstrates in silico modeling of monoclonal antibody cetuximab (CET MAb)-conjugated docetaxel (DOCT)-loaded poly(γ-glutamic acid) (γ-PGA) nanoparticles (Nps) and evaluates the in vitro/in vivo effects on EGFR-overexpressing gastric cancer cells (MKN-28). Nontargeted DOCT-γ-PGA Nps (NT Nps: 110±40 nm) and targeted CET MAb-DOCT-γ-PGA Nps (T Nps: 200±20 nm) were prepared using ionic gelation followed by 1-Ethyl-3-(3-dimethyl aminopropyl)carbodiimide-N-Hydoxysuccinimide (EDC-NSH) chemistry. Increased uptake correlated with enhanced cytotoxicity induced by targeted Nps to EGFR +ve MKN-28 compared with nontargeted Nps as evident from MTT and flow cytometric assays. Nanoformulated DOCT showed a superior pharmacokinetic profile to that of free DOCT in Swiss albino mice, indicating the possibility of improved therapeutic effect in the disease model. Qualitative in vivo imaging showed early and enhanced tumor targeted accumulation of CET MAb-DOCT-γ-PGA Nps in EGFR +ve MKN-28-based gastric cancer xenograft, which exhibited efficient arrest of tumor growth compared with nontargeted Nps and free DOCT. Thus, actively targeted CET MAb-DOCT-γ-PGA Nps could be developed as a substitute to conventional nonspecific chemotherapy, and hence could become a feasible strategy for cancer therapy for EGFR-overexpressing gastric tumors.

Development of drug delivery systems for taxanes using ionic gelation of carboxyacyl derivatives of chitosan.

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.