ABSTRACT
Polymorphonuclear leukocytes (PMNs) provide the primary host defence against invading pathogens by producing reactive oxygen species (ROS) and microbicidal products. However, few pathogens can survive for a prolonged period of time within the PMNs. Additionally their intracellular lifestyle within the PMNs protect themselves from the additional lethal action of host immune systems such as antibodies and complements. Antibiotic delivery into the intracellular compartments of PMNs is a major challenge in the field of infectious diseases. In order to deliver antibiotics within the PMNs and for the better treatment of intracellular bacterial infections we synthesized rifampicin (RIF) loaded amorphous chitin nanoparticles (RIF-ACNPs) of 350±50 nm in diameter. RIF-ACNPs nanoparticles are found to be non-hemolytic and non-toxic against a variety of host cells. The release of rifampicin from the prepared nanoparticles was â¼60% in 24 h, followed by a sustained pattern till 72 h. The RIF-ACNPs nanoparticles showed 5-6 fold enhanced delivery of RIF into the intracellular compartments of PMNs. The RIF-ACNPs showed anti-microbial activity against Escherichia coli, Staphylococcus aureus and a variety of other bacteria. In summary, our results suggest that RIF-ACNPs could be used to treat a variety of intracellular bacterial infections.
Subject(s)
Antibiotics, Antitubercular/administration & dosage , Chitin/chemistry , Drug Delivery Systems , Nanoparticles/chemistry , Neutrophils/drug effects , Neutrophils/metabolism , Rifampin/administration & dosage , Antibiotics, Antitubercular/chemistry , Bacteria/drug effects , Biocompatible Materials/chemistry , Cell Line , Drug Liberation , Humans , Materials Testing , Nanoparticles/toxicity , Nanoparticles/ultrastructure , Rifampin/chemistry , Spectroscopy, Fourier Transform InfraredABSTRACT
This work reports the development of amidase encapsulated O-carboxymethyl chitosan nanoparticles (Ami-O-CMC NPs) of 300±50 nm size by ionic cross-linking method. The prepared Ami-O-CMC NPs had an encapsulation efficiency of 55.39%. Haemolysis assay and cytotoxicity studies proved the hemocompatibility and cytocompatibility of the prepared NPs. The sustained release of Ami from the NPs is expected to prolong its immunogenicity and in turn lead to development of better protective immunity against Staphylococcus aureus infections.
Subject(s)
Amidohydrolases/chemistry , Chitosan/analogs & derivatives , Drug Delivery Systems , Staphylococcus aureus/drug effects , Chitosan/administration & dosage , Chitosan/chemistry , Humans , Immunotherapy, Active , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcal Infections/pathologyABSTRACT
Chitin and its derivatives have been widely used in drug delivery applications due to its biocompatible, biodegradable and non-toxic nature. In this study, we have developed amorphous chitin nanoparticles (150±50 nm) and evaluated its potential as a drug delivery system. Paclitaxel (PTX), a major chemotherapeutic agent was loaded into amorphous chitin nanoparticles (AC NPs) through ionic cross-linking reaction using TPP. The prepared PTX loaded AC NPs had an average diameter of 200±50 nm. Physico-chemical characterization of the prepared nanoparticles was carried out. These nanoparticles were proven to be hemocompatible and in vitro drug release studies showed a sustained release of PTX. Cellular internalization of the NPs was confirmed by fluorescent microscopy as well as by flow cytometry. Anticancer activity studies proved the toxicity of PTX-AC NPs toward colon cancer cells. These preliminary results indicate the potential of PTX-AC NPs in colon cancer drug delivery.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Chitin/chemistry , Colonic Neoplasms/drug therapy , Drug Delivery Systems , Nanoparticles/chemistry , Paclitaxel/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Colonic Neoplasms/pathology , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Flow Cytometry , HT29 Cells , Humans , Paclitaxel/chemistry , Particle Size , Structure-Activity Relationship , Surface Properties , Tumor Cells, CulturedABSTRACT
Intracellular bacterial infections are recurrent, persistent and are difficult to treat because of poor penetration and limited availability of antibiotics within macrophages and epithelial cells. We developed biocompatible, 200 nm sized tetracycline encapsulated O-carboxymethyl chitosan nanoparticles (Tet-O-CMC Nps) via ionic gelation for its sustained delivery of Tet into cells. S. aureus binds and aggregates with Tet-O-CMC Nps increasing drug concentrations at the infection site. Tet-O-CMC Nps were sixfold more effective in killing intracellular S. aureus compared to Tet alone in HEK-293 and differentiated THP1 macrophage cells proving it to be an efficient nanomedicine to treat intracellular S. aureus infections.