No abstract

We conclude that the PS targeting moiety can provide a new insight for efficient drug delivery to specialized macrophages and thus may be developed for effective use in macrophage-specific delivery systems, especially for leishmaniasis.

Pharmacotherapy of various disease states can be amended by drug repurposing through GRDDS. Assessment of the effect of the fed and fasted condition on product performance should be necessary during initial development phases. Dual working technology would be a possible way to overcome drawbacks associated with different GRDDS. Before development of a drug product, the principles of scale up and process validation must be considered to improve the quality and market availability of GRDDS. Knowledge of all regulatory aspects will help to deliver a product to the market within a reasonable timeframe and in a cost-effective manner.

Adhesion forces of nanoparticulate materials toward biological membrane are crucial for designing a delivery system for therapeutic molecules and vaccines. The present study aims to investigate the impact of surface roughness of the nanoparticulate system in oral delivery of antigen and its targeting to toward intestinal antigen presenting cells. To evaluate this hypothesis, layer-by-layer coated liposomes (LBL-Lipo) were fabricated using sodium alginate and Vitamin B12 conjugated Chitosan (VitB12-Chi) as anionic and cationic polyelectrolyte, respectively. Change in surface roughness was observed on changes in pH from gastric to intestinal conditions attributed to increase and decrease in charge density on VitB12-Chi. Surface roughness was measured in terms of root-mean-square measured by topographical analysis using atomic force microscopy. LBL-Lipo were further characterized for their size, zeta potential, and release behavior to evaluate the potential for oral vaccine delivery. In vitro cell uptake in macrophage cells (J-744) shows about 2- and 3.1-fold increased uptake of rough LBL-Lipo over smooth LBL-Lipo at 37 °C (endocytosis) and 4 °C (endocytosis inhibition) indicating improved biological interaction. Further in vivo immunization study revealed that prototype formulations were able to produce 4.8- and 3.3-fold higher IgG and IgA levels in serum and feces, respectively, in comparison to smooth LBL-Lipo.

The objective of the preparation was achieved and high accumulation of AmB in liver and spleen has been found, which resulted in enhanced anti-leishmanial activity.

The present study was focused on the development of surface modified gelatin nanoparticles (SGNPs) using novel ligand 4-sulfated N-acetyl galactosamine (4-SO(4)GalNAc) for specific targeting to macrophages. The gelatin has been modified with the potential targeting moiety 4-SO(4)GalNAc, which was further used for the preparation of modified nanoparticles. The nanoparticles have been prepared by two step desolvation method. The SGNPs and unmodified gelatin nanoparticles (GNPs) were loaded with doxorubicin (DxR) and its targeting potential was compared. Developed DxR-loaded SGNPs (DxR-SGNPs) were found to have negative zeta potential (-19.8 ± 0.22 mV) whereas DxR-loaded GNPs (DxR-GNPs) have the positive zeta potential of around +12.2 ± 0.36 mV. The mean particle size of DxR-SGNPs and DxR-GNPs was found to be 283 ± 7 and 134 ± 5 nm, respectively. Flow cytometric data confirmed the enhanced uptake of DxR-SGNPs in J774A.1 and PBMC when compared with DxR-GNPs. Intracellular localization studies indicate that the fluorescence intensity of DxR-SGNPs was significantly higher when compared to DxR-GNPs. DxR-SGNPs rendered significantly higher localization of DxR in liver and spleen as compared to DxR-GNPs after i.v. administration. The study stipulates that 4-SO(4)GalNAc assures for targeting resident macrophages.

Selection of PEs for the fabrication of LbL microcapsules has a profound effect on stability, drug release, biocompatibility and encapsulation efficacy. The release can be easily modulated by varying different physicochemical as well as physiological conditions. Scale-up approaches for the fabrication of LbL microcapsules by means of automation must be considered to improve the possibility of application of LbL microcapsules on a large scale.

BACKGROUND AND PURPOSEThe aim of the present study was to evaluate the immunomodulatory and chemotherapeutic potential of alginate-(SA) coated nanocapsule (NCs) loaded with doxorubicin (SA-NCs-DOX) against visceral leishmaniasis in comparison with nano-emulsions containing doxorubicin (NE-DOX). EXPERIMENTAL APPROACHNE-DOX was prepared using low-energy emulsification methods. Stepwise addition of protamine sulphate and SA in a layer-by-layer manner was used to form SA-NCs-DOX. SA-NCs-DOX, NE-DOX and Free DOX were compared for their cytotoxicity against Leishmania donovani-infected macrophages in vitro and generation of T-cell responses in infected hamsters in vivo. KEY RESULTSSize and ζ potential of the NE-DOX and SA-NCs-DOX formulations were 310 ± 2.1 nm and (−)32.6 ± 2.1 mV, 342 ± 4.1 nm and (−)29.3 ± 1.2 mV respectively. SA-NCs-DOX was better (1.5 times) taken up by J774A.1 macrophages compared with NE-DOX. SA-NCs -DOX showed greater efficacy than NE-DOX against intramacrophagic amastigotes. SA-NCs-DOX treatment exhibited enhanced apoptotic efficiency than NE-DOX and free DOX as evident by cell cycle analysis, decrease in mitochondrial membrane potential, ROS and NO production. T-cell responses, when assessed through lymphoproliferative responses, NO production along with enhanced levels of iNOS, TNF-α, IFN-γ and IL-12 were found to be up-regulated after SA-NCs-DOX, compared with responses to NE-DOX in vivo. Parasitic burden was decreased in Leishmania-infected hamsters treated with SA-NCs-DOX, compared with NE-DOX. CONCLUSIONS AND IMPLICATIONSOur results provide insights into the development of an alternative approach to improved management of leishmaniasis through a combination of chemotherapy with stimulation of the innate immune system.