ABSTRACT
The extensive advancement with novel wound dressing materials functionalized with desirable properties, often touted as a panacea for cuts and burns afflicting various pathologies. However, it would indeed be a hard task to isolate any such material which perfectly fits the needs of any biomedical issue at hand. Biocompatibility, biodegradability as well as non-toxicity of natural polysaccharide served as a versatile and tunable platform for designing natural polysaccharide based scaffolds as an attractive tool in tissue engineering with a greater degree of acceptability. In this regard, we aimed to fabricate a semi interpenetrating hydrogel via exploiting the nontoxic and immune-stimulatory nature of galacto-xyloglucan (PST001) which was further doped with silver nanoparticles to formulate SNP@PST. The wound healing potential of SNP@PST was then studied both with in vitro and preclinical mice models. The current study gives a formulation for cost effective preparation of polysaccharide hydrogels using acrylamide crosslinking with improved biocompatibility and degradability. Wound healing studies in mice proved the efficiency of gels for the clinical application wherein the incorporation of nanosilver greatly enhanced the antimicrobial activity.
Subject(s)
Anti-Bacterial Agents/chemistry , Glucans/chemistry , Hydrogels/chemistry , Metal Nanoparticles/chemistry , Plant Extracts/chemistry , Silver/chemistry , 3T3 Cells , Administration, Cutaneous , Animals , Anti-Bacterial Agents/pharmacology , Biocompatible Materials/chemistry , Male , Mice , Mice, Inbred BALB C , Permeability , RAW 264.7 Cells , Seeds/chemistry , Silver/pharmacology , Tamarindus/chemistry , Tissue Engineering , Tissue Scaffolds/chemistry , Wound Healing/drug effectsABSTRACT
A variety of naturally derived and synthetic biomaterial scaffolds have been investigated as 3D environments for supporting cell growth and can be used to achieve drug delivery with high loading efficiency. Polysaccharides which enhance the tumour-specific drug release are ideal candidates for scaffold preparation in combination with chemotherapeutic agents for the management of solid tumours by local applications. Galactoxyloglucan (PST001) based porous scaffolds (PS) were prepared by crosslinking and freeze drying with a porosity of 90%. FTIR showed the same functional groups as of PST001 with slight peak shifts and 1200% water absorption was observed. Comparing with PBS, macrophage mediated improved degradation up to 40% in 28 days was observed. The scaffold was relatively non toxic towards normal and cancer cells and there was no epithelial mesenchymal transition (EMT) observed. In vitro drug release profile of doxorubicin (DOX)-loaded scaffold (PSD) showed higher release at acidic pH, apparent in tumour microenvironment, than normal physiological pH. In in vitro assays, cell viability was decreased confirming the drug release potential of the scaffold. DLA tumour was significantly reduced with PSD implantation. The excellent biodegradability of the PS overcome the limitations of non-biodegradable systems which support the sustained release of the drug and degrade after a specific time period. The local tumour reduction potential of the PSD embrace immense application in malignant solid tumour management.
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Doxorubicin/administration & dosage , Drug Delivery Systems/methods , Polysaccharides/chemistry , 3T3-L1 Cells , Absorbable Implants , Animals , Antibiotics, Antineoplastic/pharmacokinetics , Cell Line, Tumor , Doxorubicin/pharmacokinetics , Drug Implants , Drug Liberation , Epithelial-Mesenchymal Transition/drug effects , Humans , Male , Materials Testing , Mice , Polysaccharides/pharmacokinetics , Porosity , Rats, Wistar , Xenograft Model Antitumor AssaysABSTRACT
Paclitaxel, an effective chemotherapeutic drug, is insoluble in aqueous solvents and is usually administered with excipients which have side effects. The use of this drug is also limited due to multi-drug resistance. In this study polysaccharide nanoparticles are used in the delivery of chemotherapeutic drug while minimizing side-effects, solubility issues and drug resistance. The use of biopolymers like galactoxyloglucan to synthesize nanoparticle makes it more biocompatible. This study involves the synthesis of PST-PTX nanoparticles using tamarind seed polysaccharide and Paclitaxel by epichlorohydrin crosslinking. The particles were further characterized by Dynamic Light Scattering (DLS), High-resolution transmission electron microscopy (HR-TEM) Fourier Transform Infrared Spectroscopy (FTIR) and UV-Visible spectroscopy. The cytotoxicity of PST-PTX nanoparticles in cancer cell lines and resistant cancer cell lines were determined by MTT assay. The quantitative analysis of cell death was determined by Annexin V dead cell assay, Caspase 3/7 assay and expression of pro-apoptotic protein Bax. The ability of the nanoparticle to overcome multi-drug resistance was evaluated by the expression of multidrug-resistant proteins P-glycoprotein (P-gp) and Breast cancer resistant protein (BCRP) in lung adenocarcinoma resistant cells (A549R). The present study provides evidence for the ability of PST-PTX nanoparticle to overcome multi-drug resistance and cause apoptotic cell death. The particle was found to be more effective than Paclitaxel in causing cell death in resistant cancer cells. Moreover, the particles were found to downregulate the expression of multi-drug resistant proteins P-gp and BCRP in resistant cell lines suggesting the ability of PST-PTX nanoparticles to overcome multi-drug resistance.
