Nanoscale drug delivery strategies for therapy of ovarian cancer: conventional vs targeted.

Ovarian cancer is the second most common gynaecological malignancy. It usually occurs in women older than 50 years, and because 75% of cases are diagnosed at stage III or IV it is associated with poor diagnosis. Despite the chemosensitivity of intraperitoneal chemotherapy, the majority of patients is relapsed and eventually dies. In addition to the challenge of early detection, its treatment presents several challenges like the route of administration, resistance to therapy with recurrence and specific targeting of cancer to reduce cytotoxicity and side effects. In ovarian cancer therapy, nanocarriers help overcome problems of poor aqueous solubility of chemotherapeutic drugs and enhance their delivery to the tumour sites either by passive or active targeting, and thus reducing adverse side effects to the healthy tissues. Moreover, the bioavailability to the tumour site is increased by the enhanced permeability and retention (EPR) mechanism. The present review aims to describe the current conventional treatment with special reference to passively and actively targeted drug delivery systems (DDSs) towards specific receptors designed against ovarian cancer to overcome the drawbacks of conventional delivery. Conclusively, targeted nanocarriers would optimise the intra-tumour distribution, followed by drug delivery into the intracellular compartment. These features may contribute to greater therapeutic effect.

Evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine.

The aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (A-CHMp) for oral vaccine against anthrax. The zeta potential of A-CHMp was -29.7 mV, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. The results indicated that A-CHMp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. The immunization studies indicated that A-CHMp resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response. Thus, A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax.

Options and opportunities for clinical management and treatment of psoriasis.

Psoriasis is a complex, multifactorial disease that appears to be influenced by immune-mediated components. For many years the pathogenesis of psoriasis has been discordant; the clinical picture suggested that the psoriasis was secondary to abnormal keratinocyte proliferation and differentiation, but later the role of the T cell was revealed. A variety of treatment options range from topical agents (e.g., coal tar, dithranol, and emollients for milder forms) to systemic agents (i.e., methotrexate or cyclosporin), and phototherapy. Recently, biologics have been added to this list that target particular steps in the immune or inflammatory pathways. Various nanocarriers (e.g., liposomes, niosomes, and microemulsions) have been successfully exploited for the delivery of several antipsoriatic drugs. This review provides insight into various psoriasis treatment strategies-from conventional to novel-currently in use or in development as well as the novel targets that have been explored and/or investigated for anti-psoriatic therapy. The pathogenesis of psoriasis and some of the topical, systemic biological, and novel approaches currently in use or in development are reviewed here. The pros and cons of each treatment strategy are presented, as are some of the animal models used to study features reminiscent of psoriasis. This information can be used to better the understanding of treatment options for this disease.

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.

Development of a single-dose stabilized poly(D,L-lactic-co-glycolic acid) microspheres-based vaccine against hepatitis B.

The purpose of this study was to develop a stable single-dose vaccine based on recombinant hepatitis B surface antigen (HBsAg) in poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres, in which HBsAg was stabilized by a protein stabilizer (trehalose) and an antacid (Mg(OH)2). The microspheres were prepared by the double emulsion method and characterized by scanning electron microscopy. To neutralize the acids liberated by the biodegradable lactic/glycolic acid based polymer, we coincorporated into the polymer an antacid, Mg(OH)2, which neutralized the acidity during degradation of the polymer and also prevented HBsAg structural losses and aggregation. The antigen integrity after encapsulation was examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by silver staining, isoelectric focusing and Western blotting techniques, which confirmed that antigen remained intact after encapsulation. In-vitro release experiments were performed in phosphate-buffered saline (pH 7.4) and the release of antigen was found to be improved by the protein stabilizer (trehalose). In stability studies, performed at 37 degrees C, the microspheres were found to be stable for 16 days. The immunogenicity of stable microsphere formulations bearing HBsAg was compared with the conventional alum-absorbed HBsAg vaccine in a guinea-pig model. The antibody titre indicated that a single injection of stabilized HBsAg-PLGA microspheres produced a better immune response than two injections of alum-formulated HBsAg vaccine. The findings suggest that recombinant HBsAg can be stabilized by use of a protein stabilizer and antacid during entrapment, and this stabilized preparation can be useful for antigen delivery.

Immunomodulatory effects of aqueous extract of Tridax procumbens in experimental animals.

The immunomodulatory properties of ethanol insoluble fraction of aqueous extract of Tridax procumbens Linn. (TPEIF) have been investigated. After intraperitoneal administration of TPEIF in doses of 0.25 and 0.5 g/kg body weight (BW) a significant increase in phagocytic index, leukocyte count and spleenic antibody secreting cells was noticed. Stimulation of humoral immune response was further observed with elevation in heamagglutination antibody titer. Heightened delayed type hypersensitivity reaction suggested convincing evidence for activation of cellular immune system. Protective action of herbal medicine in case of anaphylactic shock was also studied. In addition, elicitation of specific antibody titer against tetanus toxoid (TT) challenge was measured in order to explore the possible use as adjuvant along with clinical vaccination program to reduce number of non-responders. The results suggest that TPEIF influences both humoral as well as cell mediated immune system vis-a-vis assists in genesis of improved antibody response against specific clinical antigen.