Dual antitubercular drug loaded liposomes for macrophage targeting: development, characterisation, ex vivo and in vivo assessment.

AIM: The present study was conducted to formulate and investigate liposomes for the dual drug delivery based on anti-tubercular drug(s) combination i.e. Isoniazid (INH) and Rifampicin (RIF). MATERIALS AND METHODS: Mannosylated and non mannosylated liposomes were prepared by lipid thin film hydration method, using DSPC: Chol at a molar ratio 6:4 while in case of mannosylated liposomes DSPC: Chol: Man-C4-Chol at a molar ratio 6.0:3.5:0.5 were used and extensively characterised. The particle size and zeta potential were recorded to be 1.29 ± 0.24 µm and -9.1 ± 0.11 mV. The drug entrapment (%) was recorded to be 84.7 ± 1.25% for Rifampicin and 31.8 ± 0.12% for Isoniazid. RESULTS: The antitubercular activity studied in Balb/C mice was maximum in the case of mannosylated liposomes. The biodistribution studies also revealed higher drug(s) concentration (accumulation) maintained over a protracted period. CONCLUSIONS: The liposomal preparations are passively as well as actively uptaken by the alveolar macrophages which are the cellular tropics of infection. The mannosylated liposomes appear to be a potential carrier for dual drug delivery and targeted antitubercular therapy.

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.

Tuberculosis: from molecular pathogenesis to effective drug carrier design.

In the past two decades, tuberculosis has gone from being a forgotten disease to a modern and recrudescent pathology. Tuberculosis is a curable infection and most of the negative therapeutic outcomes are related to poor patient compliance, which could be solved by new drug delivery approaches. By using such approaches the technological drawbacks of the currently used therapeutic agents could be addressed. In addition, optimum effectiveness of the drug by targeting the infection reservoirs could be achieved. In this article we compile the general physiological aspects of the infection along with new research updates especially on novel carriers used in the prevention of tuberculosis which might enhance therapeutic efficacy and patient compliance.

Recent advances in mucosal delivery of vaccines: role of mucoadhesive/biodegradable polymeric carriers.

IMPORTANCE OF THE FIELD: The mucosal delivery of vaccines provides the basis for induction of humoral, cellular and mucosal immune responses against infectious diseases. The delivery of antigens to and through mucosal barriers always remains challenging due to adverse physiological conditions (pH and enzymes) and biological barriers created by tight epithelial junctions restricting transportation of macromolecules. Mucoadhesive and biodegradable polymers offer numerous advantages in therapeutic delivery of proteins/antigens particularly through the mucosal route by protecting antigens from degradation, increasing concentration of antigen in the vicinity of mucosal tissue for better absorption, extending their residence time in the body and/or targeting them to sites of antigen uptake. Furthermore, antigen can be delivered more effectively to the antigen presenting cells by anchoring the ligand having affinity on the surface of carrier for the receptors present on the mucosal epithelial cells. AREAS COVERED IN THIS REVIEW: The present review covers various polymeric carriers, which allow the possibility of modification and manipulation of their properties, thereby, enhancing the effectiveness of mucosal vaccines. This article reviews the recent literature and patents in the field of vaccine delivery using mucoadhesive polymeric carriers. WHAT THE READER WILL GAIN: The reader will gain insights into various natural polymers, synthetic polymers and ligand derived polymeric carrier systems studied to enhance mucosal immunization. TAKE HOME MESSAGE: Biodegradable polymeric carriers represent a promising approach for mucosal delivery of vaccine.

Development and characterization of effective topical liposomal system for localized treatment of cutaneous candidiasis.

The localized delivery of fluconazole (FLZ) by conventional therapy is a major impediment in achieving its therapeutic efficacy against skin infections, such as cutaneous candidiasis. Therefore, the present study was aimed to develop FLZ-loaded vesicular construct(s), such as liposomes and niosomes, incorporated into carbopol gel (1%; w/w) for sustained, localized application. The liposomes and niosomes were prepared by the lipid/nonionic surfactant-based dry-film hydration method and were characterized for different parameters. In addition, antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed albino rats. The results showed that the size of liposomes and niosomes was found to be 0.348 ± 0.054 and 0.326 ± 0.033 µm with encapsulation efficiency of 31.8 ± 1.36 and 27.6 ± 1.08%, respectively. The skin-retention studies of FLZ from in vitro and in vivo experiments showed significantly higher accumulation of drug in the case of liposomal gel. The in vivo localization studies in viable skin showed that liposomal gel could produce 14.2-fold higher drug accumulation, compared with plain gel, while it was 3.3-fold more in the case of an equivalent-dose application in the form of niosomal gel. The antifungal study also confirmed the maximum therapeutic efficacy of liposomal gel, as the lowest number of cfu/mL was recorded following liposomal FLZ application. The studies signify the potential of liposomal gel for topical delivery of FLZ with increased accumulation of drug in various strata of skin vis-a-vis through sustained release of drug could maintain the localized effect, resulting in an effective treatment of a life-threatening cutaneous fungal infection.

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.

Targeted nucleic acid delivery to mitochondria.

Mitochondrial genetics has become an emerging area of research in the field of modern therapeutics. Mitochondrial genome is the source of 13 polypeptides which are components of subunits of complexes of electron transport chain and are used in the generation of ATP by oxidative phosphorylation. Any mutation and/or defects in these mitochondrial genes may cause diseases ranging from neurodegenerative diseases, diabetes mellitus to cancer. In an ideal condition mtDNA should be mutation free. There are various mechanisms for the repair of diseased cell or mitochondrial DNA. Nowadays, nucleic acid based therapeutics has become of interest and represent a new area of research. However, problem consistently encountered is safe and effective delivery of DNA to the mitochondria for therapeutic benefits. There are numerous barriers which are to be surpassed for successful delivery of nucleic acid to the cell interior and ultimately to the mitochondria. For efficient and effective DNA delivery to the mitochondrial matrix, a suitable carrier system is required to be designed and developed. In the present review we have discussed briefly about mitochondrial DNA and related diseases, various barriers encountered in the delivery of DNA, internalization processes, delivery strategies and methods for targeted delivery of DNA to the mitochondria.