ABSTRACT
The present study explores prospective of surface tailored nanoparticles for targeted delivery of acyclovir along with the interception of minimal side effects. Acyclovir loaded plain and galactosylated poly lectic co glycolic acid (PLGA) nanoparticles were efficiently prepared and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), size, polydispersity index, zeta potential, and entrapment efficiency. The formulations were evaluated for in vitro drug release and hemolysis. Further, biodistribution study and fluorescent microscopic studies were carried out to determine the targeting potential of formulations. SEM revealed smooth morphology and spherical shape of the nanoparticles. In vitro, the galactosylated nanoparticles were found to be least hemolytic and exhibited a sustained release pattern. In vivo studies exhibited an augmented bioavailability, increased residence time and enhanced delivery of acyclovir to the liver upon galactosylation. It may therefore be concluded that galactose conjugated PLGA nanoparticles can be used suitably as vehicles for delivery of bioactives specifically to the hepatic tissues and may be thus exploited in the effective management of various liver disorders.
Subject(s)
Acyclovir/administration & dosage , Antiviral Agents/administration & dosage , Galactose/chemistry , Lactic Acid/chemistry , Polyglycolic Acid/chemistry , Acyclovir/pharmacokinetics , Acyclovir/toxicity , Animals , Antiviral Agents/pharmacokinetics , Antiviral Agents/toxicity , Chemistry, Pharmaceutical , Delayed-Action Preparations , Drug Carriers/chemistry , Drug Compounding , Drug Delivery Systems , Female , Glycolates/chemistry , Hemolysis/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred BALB C , Microscopy, Fluorescence , Nanoparticles , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer , Spectroscopy, Fourier Transform Infrared , Surface Properties , Tissue DistributionABSTRACT
The aim of the present investigation was to evaluate the prospective of surface-engineered vesicular carriers for mucosal immunization via the nasal route. IgG antibody was immobilized on the surface of hepatitis B surface antigen (HBsAg) antigen-loaded liposomes. The developed formulations were characterized on the basis of physicochemical parameters, such as morphology, particle size, polydispersity index, entrapment efficiency, and zeta potential. Liposomal formulations were then evaluated for in-process antigen stability and storage stability. In vivo studies were conducted to visualize targeting potential, localization pattern, and immunogenicity. In addition, immune response was compared with alum-HBsAg vaccine injected intramuscularly. The serum anti-HBsAg titer, obtained from the postnasal administration of IgG-coupled liposomes, was significantly higher than plain liposomes. Moreover, IgG-coupled liposomes generated both humoral (i.e., systemic and mucosal) and cellular immune responses upon nasal administration, while the alum-adsorbed antigen displayed neither cellular (cytokine level) nor mucosal (IgA) response. The formulation also displayed enhanced transmucosal transport, improved in vitro stability, and effective immunoadjuvant property. To conclude, IgG antibody-coupled liposomes may serve as novel carriers to augment the secretory immune response of antigen encapsulated in the liposomes, apparently by escalating liposome uptake via M cells, thereby rationalizing their use as a carrier adjuvant for nasal subunit vaccines.
Subject(s)
Administration, Intranasal , Drug Carriers/chemistry , Drug Carriers/metabolism , Immunoglobulin G/immunology , Liposomes/chemistry , Mucous Membrane/immunology , Vaccination/methods , Animals , Female , Hepatitis B Surface Antigens/chemistry , Hepatitis B Surface Antigens/immunology , Liposomes/immunology , Liposomes/ultrastructure , Mice , Mice, Inbred BALB C , Molecular StructureABSTRACT
Blood Brain Barrier (BBB) represents a major hurdle for the delivery of bioactives in the brain. It serves as a major constraint for the entry of hydrophilic drugs and the efflux pumps present on its surface restrain the intracellular accumulation of pharmacological moieties in the brain. Nanoparticles (NPs) in this regard can serve as a potential module for ferrying large doses of drugs across the BBB. These can be coated at surfaces or fabricated with a targeting moiety, so as to gain access in the brain thus, minimizing the toxicity of therapy. Therefore, the NPs can serve as an exclusive dais for spatial and temporal distribution of pharmacological agents across the brain, escalating the probability of disease free survival. The current review explores the various possible mechanisms so that the NPs can gain access in the brain viz a viz adsorption, receptor mediated endocytosis, transcytosis, inhibiting p-glycoprotein efflux pump, membrane permeabilization effect and disrupting the BBB. The article also accounts the prospects of NPs to enhance the transport of therapeutic agents across the brain, providing refined drug delivery.
