Depot based drug delivery system for the management of depression.

Depression is a common mental disorder discerns with depressed mood, loss of interest, the primary treatment methods are drug therapy, electroconvulsive therapy, psychotherapy, light therapy, vagus nerve stimulation, etc. A number of innovative delivery systems have been developed to address suboptimal therapy outcomes by enhancing drug delivery, assuring efficacy of treatment, reducing side effects, improving compliance and drug targeting specific locations resulting in a higher efficiency. Depot delivery offers the advantage of a very high loading, controlled release of drug for an extended period of time and reduces frequency of dosing. The increase in AUC and decrease in Cmax reflects that the depot formulations could reduce the toxic complications and limitations of conventional and oral therapies. Products at preclinical and clinical stages include formulations of naltrexone and buprenorphine for alcoholism/drug abuse, GLP-1 peptides for diabetes, r-hFSH for fertility, dopamine for nerve growth, dexamethasone for ocular treatment, melanotan for cancer prevention, plasmid DNA for cancer prevention, a variety of vaccines, octreotide generics, etc. Most depot formulations are comprised of biodegradable polymer-excipients that control the rate of drug release and resorbs during/after drug release. The major advantage of depot antipsychotics over oral medication was facilitation of compliance in medication taking. One class of biodegradable polymers that has gained wide acceptance and still attractive today is lactide/glycolide polymers. The greatest advantage of these degradable polymers is that they are broken down into biologically acceptable molecules that are metabolized and removed from the body via normal metabolic pathways. This versatile delivery system offers the advantage of a very high loading and controlled release of various drug for an extended period of time compared with plain delivery system. New formulations of depression can offer advantages over older formulations in terms of convenience, side effect profiles, efficacy, and/or a fast onset of action.

Preparation and evaluation of galactosylated vesicular carrier for hepatic targeting of silibinin.

PURPOSE: Silibinin, the main flavonolignan of Silymarin, is used in the treatment of liver diseases of varying origins. Aiming at improving its poor bioavailability of oral products, galactosylated liposomes were introduced in this work for silibinin delivery and targeting to the lectin receptors present on the hepatocytes. METHODS: Small unilamellar liposomal vesicles were prepared and p-aminophenyl-beta-d-galactopyranoside was covalently coupled. The drug release from liposomes was studied by dialysis method. Plasma, tissue distribution and intrahepatic distribution of free, plain liposomal and galactosylated liposomal encapsulated silibinin were determined following a bolus intravenous injection in albino rats. Various formulations were evaluated regarding silibinin's hepatoprotective activity against CCl(4)-induced oxidative stress in albino rats. The degree of protection was measured using biochemical parameters like serum glutamic oxalacetate transaminase and serum glutamic pyruvate transaminase. RESULTS: Aggregation of galactosylated liposomes by Ricinus communis revealed the presence of galactose residues on the surface of liposomes. After 24 hours, cumulative drug release percent from galactosylated liposomes was found to be moderate (30.9 +/- 1.73%). The results of tissue distribution study indicated extensive localization of liposomal formulations in liver cells (galactosylated liposomes, 61.27 +/- 3.84% in 1 hour). Separation of the liver cells showed that galactosylated liposomes were preferentially taken up by the hepatocytes (79% of the total hepatic uptake in 1 hour). The introduced galactosylated silibinin produced a significant decrease in both transaminase levels when challenged with CCl(4) intraperitonially. CONCLUSION: A positive outcome of these studies gave an insight that galactosylated liposomes are more effective and suitable for targeted delivery of silibinin to hepatocytes.

Development of self-assembled nanoceramic carrier construct(s) for vaccine delivery.

Hydroxyapatite (HA) has been extensively investigated as scaffolds for tissue engineering, as drug delivery agents, as non-viral gene carriers, as prosthetic coatings, and composites. Recent studies in our laboratory demonstrated the immunoadjuvant properties of HA when administered with malarial merozoite surface protein-1(19) (MSP-1(19)). HA nanoceramic carrier was prepared by co-precipitation method that comprises of sintering and spray-drying technique. Prepared systems were characterized for crystallinity, size, shape, and antigen loading efficiency. Small size and large surface area of prepared HA demonstrated good adsorption efficiency of immunogens. Prepared nanoceramic formulations also showed slower in vitro antigen release and slower biodegrability behavior, which may lead to a prolonged exposure to antigen-presenting cells and lymphocytes. Furthermore, addition of mannose in nanoceramic formulation may additionally lead to increased stability and immunological reactions. Immunization with MSP-1(19) in nanoceramic-based adjuvant systems induced a vigorous immunoglobulin G (IgG) response, with higher IgG2a than IgG1 titers. In addition considerable amount of IFN-g and IL-2 was observed in spleen cells of mice immunized with nanoceramic-based vaccines. On the contrary, mice immunized with MSP-1(19) alone or with alum did not exhibit a significant cytotoxic response. The antibody responses to vaccine co-administered with HA was a mixed Th1/Th2 compared to the Th2-biased response obtained with alum. The prepared HA nanoparticles exhibit physicochemical properties that appear promising to make them a suitable immunoadjuvant to be used as antigen carriers for immunopotentiation.

Nanodecoy system: a novel approach to design hepatitis B vaccine for immunopotentiation.

The progress toward subunit vaccines has been limited by their poor immunogenicity and limited stability. To enhance the immune response, subunit vaccines universally require improved adjuvants and delivery vehicles. In the present study, we propose the use of ceramic core based nanodecoy systems for effective immunization, which seems to exhibit a broad range of surface properties. Nanodecoy systems were prepared by self-assembling of hydroxyapatite core and cellobiose and finally the hepatitis B surface antigen (HBsAg) was adsorbed over the preformed nanodecoy systems. HBsAg loaded nanodecoy systems were characterized for size, shape and antigen loading efficiency. The effect of processing steps on the stability and integrity of HBsAg was assessed by in vitro antigenicity and SDS-PAGE experiments. Nanodecoy preparations were nanometric in size range and almost spherical in shape. SDS-PAGE studies confirmed the integrity of HBsAg protein in the formulation. Vaccine efficacy was determined in female Balb/c mice and results indicated that specific anti-HBsAg antibody titers in mice receiving nanodecoy system were more efficient than the conventional adjuvant alum followed by subcutaneous immunization. Studies also indicated that nanodecoy formulations could elicit combined Th1 and Th2 immune response. It is inferred that nanodecoy systems are a class of novel carriers and hold potential as an alternative adjuvant in vaccine technology.