Nanostructured Lipid Carrier-Based Delivery of Pioglitazone for Treatment of Type 2 Diabetes.

Pioglitazone (PGZ) is utilized as a therapeutic agent in the management of (type 2) diabetes to control blood glucose levels. The existing research work was intended to make and optimize PGZ-containing NLCs (nanostructured lipid carriers). The fabricated nanostructured lipid carrier preparation was optimized by using different concentrations of the surfactants (Tween 80 and Span 80) and solid lipid (Compritol® 888 ATO) and liquid lipid (Labrasol®) while keeping the concentration of drug (PGZ), and co-surfactants (poloxamer 188) the same. The optimized NLC formulation (PGZ-NLCs) was further assessed for physical and chemical characterization, in vitro PGZ release, and stability studies. The optimized PGZ-NLCs have shown an average diameter of 150.4 nm, EE of 92.53%, PDI value of 0.076, and zeta-potential of -29.1 mV, correspondingly. The DSC thermal analysis and XRD diffractograms had not presented the spectrum of PGZ, confirming the comprehensive encapsulation of PGZ in the lipid core. PGZ-NLCs showed significantly extended release (51% in 24 h) compared to the unformulated PGZ. Our study findings confirmed that PGZ-NLCs can be a promising drug delivery system for the treatment of type 2 diabetes.

Application Perspectives of Nanomedicine in Cancer Treatment.

Cancer is a disease that seriously threatens human health. Based on the improvement of traditional treatment methods and the development of new treatment modes, the pattern of cancer treatment is constantly being optimized. Nanomedicine plays an important role in these evolving tumor treatment modalities. In this article, we outline the applications of nanomedicine in three important tumor-related fields: chemotherapy, gene therapy, and immunotherapy. According to the current common problems, such as poor targeting of first-line chemotherapy drugs, easy destruction of nucleic acid drugs, and common immune-related adverse events in immunotherapy, we discuss how nanomedicine can be combined with these treatment modalities, provide typical examples, and summarize the advantages brought by the application of nanomedicine.

Controlled release floating drug delivery system for proton pump inhibitors lansoprazole: In-vitro, In-vivo floating and pharmacokinetic evaluation.

Lansoprazole (LPZ) show poor bioavailability because of first pass effect and absorption factors. The floating delivery systems could reduce fluctuations in plasma drug concentration through maintaining desirable plasma drug concentration. The objective of present study was to enhance bioavailability despite first pass effect through continuous availability of drug from floating system. Gum tragacanth (GT) and itaconic acid (IA) based floating hydrogels (FH) were synthesized. Parameters optimized were; microwave radiation exposure time, pH, GT:IA ratio and concentration of the glutaraldehyde. Optimized FH were evaluated for entrapment efficiency (% EE), in-vitro release, FTIR, SEM, and in- vitro and in-vivo floating study. Finally, pharmacokinetic was evaluated in ulcer-induced SD rats. Grafting percentage, swelling ratio and %EE of LPZ was 115%, Ì´250% and 90%, respectively. Microwave radiation exposure time, pH of reaction medium, GT:IA ratios and cross linker concentration were 2 min, pH 5, ratios 2:1 and 0.02%, respectively. The optimized FH showed acceptable floating behavior. The X-ray images revealed that hydrogels remained floated over gastric contents up to 24 hours. The in-vitro release and pharmacokinetics revealed availability of LPZ upto to 24h in-vitro and in ulcer-induced SD rats, respectively. The present hydrogels based floating system of lansoprazole is capable to extend the gastric residence time upto 24 hours.

Research progress of phosphatidylinositol 4-kinase and its inhibitors in inflammatory diseases.

Phosphatidylinositol 4-kinase (PI4K) is a lipid kinase that can catalyze the transfer of phosphate group from ATP to the inositol ring of phosphatidylinositol (PtdIns) resulting in the phosphorylation of PtdIns at 4-OH sites, to generate phosphatidylinositol 4-phosphate (PI4P). Studies on biological functions reveal that PI4K is closely related to the occurrence and development of various inflammatory diseases such as obesity, cancer, viral infections, malaria, Alzheimer's disease, etc. PI4K-related inhibitors have been found to have the effects of inhibiting virus replication, anti-cancer, treating malaria and reducing rejection in organ transplants, among which MMV390048, an anti-malaria drug, has entered phase II clinical trial. This review discusses the classification, structure, distribution and related inhibitors of PI4K and their role in the progression of cancer, viral replication, and other inflammation induced diseases to explore their potential as therapeutic targets.

Anticancer natural medicines: An overview of cell signaling and other targets of anticancer phytochemicals.

Therapies of cancer are as diverse as multifaceted the cancer is. Anticancer drugs include, but not limited to synthetic, semisynthetic and natural drugs and monoclonal antibodies. A recent decline in new drug development has led to the rebirth of herbal therapeutics in the form of dietary supplements and botanical preparations. Medicinal plants comprise of complex phytochemicals due to vast biosynthetic capacity. A wide array of phytochemicals has been pharmacologically evaluated for their chemo-preventive and chemotherapeutic potential for several decades. These phytochemicals target cancer at diverse sites such as apoptotic pathways, genetic and epigenetic mutations, damage to deoxyribonucleic acid, production of reactive oxygen species, autophagy, invasion and metastasis of cancer cells, and modulation of cell signaling through Janus-activated kinase/Signal transducer and activator of transcription, Notch, mitogen-activated protein kinase/Extracellular signal-regulated kinase, phosphatidylinositol 3-kinase/Protein kinase B/mammalian target of rapamycin, Nuclear factor kappa B, Wingless-related integration site and Transforming growth factor ß pathways. This review focuses on the therapeutic targets of anticancer and chemo-preventive phytochemicals and their mode of action.

TRPM8 channels: A review of distribution and clinical role.

Ion channels are important therapeutic targets due to their plethoric involvement in physiological and pathological consequences. The transient receptor potential cation channel subfamily M member 8 (TRPM8) is a nonselective cation channel that controls Ca2+ homeostasis. It has been proposed to be the predominant thermoreceptor for cellular and behavioral responses to cold stimuli in the transient receptor potential (TRP) channel subfamilies and exploited so far to reach the clinical-stage of drug development. TRPM8 channels can be found in multiple organs and tissues, regulating several important processes such as cell proliferation, migration and apoptosis, inflammatory reactions, immunomodulatory effects, pain, and vascular muscle tension. The related disorders have been expanded to new fields ranging from cancer and migraine to dry eye disease, pruritus, irritable bowel syndrome (IBS), and chronic cough. This review is aimed to summarize the distribution of TRPM8 and disorders related to it from a clinical perspective, so as to broaden the scope of knowledge of researchers to conduct more studies on this subject.

Pri-miR-34b/c rs4938723 Polymorphism is Associated with Decreased Risk and Better Prognosis for Colorectal Cancer Patients.

BACKGROUND: Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide. miR-34 induces changes of its downstream genes and plays a key role in altering the apoptotic cycle and pathways of downstream cells and therefore influences carcinogenesis. OBJECTIVE: The present study investigated whether the single nucleotide polymorphism rs4938723T > C in the promoter of region of miR-34b/c may increase the risk of CRC and influence outcome in patients with CRC. METHODS: We enrolled 1078 CRC patients and 1175 cancer-free controls subjects from the Chinese population. miR-34b/c rs4938723T > C polymorphisms were genotyped using a TaqMan PCR method. RESULTS: We found that subjects carrying rs4938723CT/CC genotypes have significantly decreased risk of CRC (adjusted odds ratios (AOR) = 0.75, 95% CI (0.63-0.90) for CT vs.TT; AOR = 0.61, 95% CI (0.46-0.83) for CC vs. TT and AOR = 0.73,95% CI (0.61-0.86) for CT/CC vs. TT) and a significant increased median survival time (MST) compared with those with TT genotypes (MST = 96.500; 75.883 and 71.370 months for CT, CC and CT/CC respectively vs. MST = 54.300 months for TT, p <0.0001). Stratified analysis by both life style and clinicopathological risks revealed that subjects carrying rs4938723CT/CC genotypes were remained significantly associated with increased survival and low risk of CRC compared with those with TT genotypes in all subgroup (all p <0.05). Similar observation was also reported for the prognostic value of rs4938723TC/CC genotypes across all subgroups. CONCLUSION: These findings indicate that the miR-34b/c rs4938723T > C polymorphism is an independent variable and associated with a decreased risk of CRC in Chinese population. This study provides evidence of the protective effects of rs4938723CT/CC genotypes in the development of CRC.