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Current therapies are insufficient to prevent recurrent fungal infection especially in the lower part of the lung. A careful and systematic understanding of the properties of nanoparticles plays a significant role in the design, development, optimization, and in vivo performances of the nanoparticles. In the present study, PLGA nanoparticles containing the antifungal drug voriconazole was prepared and two best formulations were selected for further characterization and in vivo studies. The nanoparticles and the free drug were radiolabeled with technetium-99m with 90% labeling efficiency, and the radiolabeled particles were administered to investigate the effect on their blood clearance, biodistribution, and in vivo gamma imaging. In vivo deposition of the drug in the lobes of the lung was studied by LC-MS/MS study. The particles were found to be spherical and had an average hydrodynamic diameter of 300 nm with a smooth surface. The radiolabeled particles and the free drug were found to accumulate in various major organs. Drug accumulation was more pronounced in the lung in the case of administration of the nanoparticles than that of the free drug. The free drug was found to be excreted more rapidly than the nanoparticle containing drug following the inhalation route as assessed by gamma scintigraphy study. Thus, the study reveals that pulmonary administration of nanoparticles containing voriconazole could be a better therapeutic choice even as compared to the iv route of administration of the free drug and/or the drug loaded nanoparticles.

A relationship between obesity and type 2 diabetes is now generally well accepted. This relationship represents several major health hazards including morbid obesity and cardiovascular complications worldwide. Diabetes mellitus is a complex metabolic disorder characterized by impaired insulin release and insulin resistance. Lipids play an important physiological role in skeletal muscle, heart, liver and pancreas. Deregulation of fatty acid metabolism is the main culprit for developing insulin resistance and type 2 diabetes. A predominant predisposing factor to developing obesity, insulin resistance and type 2 diabetes is the permanent elevation of free fatty acids in plasma followed by impaired utilization of lipids by muscle. Diabetes-induced inflammation and oxidative stress have also vital role for development of insulin resistance in diabetic patients. The present review is intended to describe the correlation between lipids, obesity and insulin resistance based on current literature, in order to elucidate involved molecular mechanisms in depth.

Betulinic acid, a plant secondary metabolite, has gained significant attention due to its antiproliferative activity over a range of cancer cells. A promising betulinic acid analogue ( 2c ) with better therapeutic efficacy than parent molecule to colon carcinoma cells has been reported. Despite impressive biological applications, low aqueous solubility and bioavailability create difficulties for its therapeutic applications. To overcome these lacunae and make it as a promising drug candidate we have encapsulated the lead betulinic acid derivative ( 2c ) in a polymeric nanocarrier system ( 2c-NP ) and evaluated its in vitro and in vivo therapeutic efficacy. Apoptosis that induces in vitro antiproliferative activity was significantly increased by 2c-NP compared to free-drug ( 2c ), as assured by MTT assay, Annexin V positivity, JC1 analysis and cell cycle study. The therapeutic potential measured in vitro and in vivo reflects ability of 2c-NP as an effective therapeutic agent for treatment of colon carcinoma and future translation to clinical trials.

Delivering highly water soluble drugs across blood–brain barrier (BBB) is a crucial challenge for the formulation scientists. A successful therapeutic intervention by developing a suitable drug delivery system may revolutionize treatment across BBB. Efforts were given here to unravel the capability of a newly developed fatty acid combination (stearic acid:oleic acid:palmitic acid = 8.08:4.13:1) (ML) as fundamental component of nanocarrier to deliver highly water soluble zidovudine (AZT) as a model drug into brain across BBB. A comparison was made with an experimentally developed standard phospholipid-based nanocarrier containing AZT. Both the formulations had nanosize spherical unilamellar vesicular structure with highly negative zeta potential along with sustained drug release profiles. Gamma scintigraphic images showed both the radiolabeled formulations successfully crossed BBB, but longer retention in brain was observed for ML-based formulation (MGF) as compared to soya lecithin (SL)-based drug carrier (SYF). Plasma and brain pharmacokinetic data showed less clearance, prolonged residence time, more bioavailability and sustained release of AZT from MGF in rats compared to those data of the rats treated with SYF/AZT suspension. Thus, ML may be utilized to successfully develop drug nanocarrier to deliver drug into brain across BBB, in a sustained manner for a prolong period of time and may provide an effective therapeutic strategy for many diseases of brain. Further, many anti-HIV drugs cannot cross BBB sufficiently. Hence, the developed formulation may be a suitable option to carry those drugs into brain for better therapeutic management of HIV.

Tumor targeted therapy has brought a new hope to the cancer patients. With the recent advances in nanotechnology and growing knowledge on unique cancer biomarkers, it is now possible to manipulate the surface architecture of polymeric nanoscale delivery systems with targeting moieties, such as antibodies, antibody fragments, specific molecules, small peptides, RNA aptamers etc. to target specific receptors and antigens present exclusively or overexpressed on the tumor cell surface or on the tumor endothelial cell surface. These modified polymeric nanoparticles deliver the loaded chemotherapeutics preferentially to the tumor tissue and not to the healthy tissue. This ensures highly targeted treatment without severe side effects which are normally experienced by the cancer patients in case of conventional chemotherapy. Such specifically constructed polymeric nanocarriers with improved tumor targeting profile are now regarded as engineered polymeric nanoparticles, which have become one of the prime areas of drug delivery research in recent times. This review describes specific approaches used in recent years to construct engineered polymeric nanoparticles, their emerging potential for cancer therapy and recent advances in tumor targeting. An equal attention has been devoted to the fundamental problems encountered in practical fields which limit their clinical use and industrial production.

Background and objectiveTargeted drug delivery of nanoparticles decorated with site-specific recognition ligands is of considerable interest to minimize cytotoxicity of chemotherapeutics in the normal cells. The study was designed to develop CD-340 antibody-conjugated polylactic-co-glycolic acid (PLGA) nanoparticles loaded with a highly water-soluble potent anticancer drug, doxorubicin (DOX), to specifically deliver entrapped DOX to breast cancer cells.MethodsThe study showed how to incorporate water-soluble drug in a hydrophobic PLGA (85:15) based matrix which otherwise shows poor drug loading due to leaching effect. The optimized formulation was covalently conjugated to anti-human epidermal growth factor receptor-2 (HER2) antibody (CD-340). Surface conjugation of the ligand was assessed by flow cytometry, confocal microscopy, and gel electrophoresis. Selectivity and cytotoxicity of the experimental nanoparticles were tested on human breast cancer cells SKBR-3, MCF-7, and MDA-MB-231. Both CD-340-conjugated and unconjugated nanoparticles were undergone in vitro and in vivo characterization.ResultHigher level of incorporation of DOX (8.5% W/W), which otherwise shows poor drug loading due to leaching effect of the highly water-soluble drug, was seen in this method. In HER2-overexpressing tumor xenograft model, radiolabeled antibody-conjugated nanoparticles showed preferentially more of the formulation accumulation in the tumor area when compared to the treatments with the unconjugated one or with the other control groups of mice. The ligand conjugated nanoparticles showed considerable potential in reduction of tumor growth and cardiac toxicity of DOX in mice, a prominent side-effect of the drug.ConclusionIn conclusion, CD-340-conjugated PLGA nanoparticles containing DOX preferentially delivered encapsulated drug to the breast cancer cells and in breast tumor and reduced the breast tumor cells by apoptosis. Site-specific delivery of the formulation to neoplastic cells did not affect normal cells and showed a drastic reduction of DOX-related cardiotoxicity.

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