Atomic Force Microscopy Images Label-Free, Drug Encapsulated Nanoparticles In Vivo and Detects Difference in Tissue Mechanical Properties of Treated and Untreated: A Tip for Nanotoxicology

Overcoming the intractable challenge of imaging of label-free, drug encapsulated nanoparticles in tissues in vivo would directly address associated regulatory concerns over 'nanotoxicology'. Here we demonstrate the utility of Atomic Force Microscopy (AFM) for visualising label-free, drug encapsulated polyester particles of ~280 nm distributed within tissues following their intravenous or peroral administration to rodents. A surprising phenomenon, in which the tissues' mechanical stiffness was directly measured (also by AFM) and related to the number of embedded nanoparticles, was utilised to generate quantitative data sets for nanoparticles localisation. By coupling the normal determination of a drug's pharmacokinetics/pharmacodynamics with post-sacrifice measurement of nanoparticle localisation and number, we present for the first time an experimental design in which a single in vivo study relates the PK/PD of a nanomedicine to its toxicokinetics

Ternarna kompleksacija karvedilola, β-ciklodekstrina i limunske kiseline za razvoj tableta topljivih u ustima

The purpose of this study was to improve the solubility and dissolution rate of carvedilol by forming a ternary complex with β-cyclodextrin and citric acid and to formulate its mouth-dissolving tablets. The rationale for preparing mouth-dissolving tablet of carvedilol was to make the drug available in a soluble form in the mouth, which would facilitate its absorption from ther buccal cavity. Phase solubility studies revealed the ability of β-cyclodextrin and citric acid to complex with carvedilol and significantly increase its solubility. Ternary complexation of carvedilol was carried out with β-cyclodextrin and citric acid by physical mixing, kneading and spray drying methods and the prepared complexes were characterized by Fourier transform infra red spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and complexation efficiency. The complex obtained by the spray drying method resulted in highest complexation efficiency and a 110-fold increase in the solubility of carvedilol. The mouth-dissolving tablets formulated using the spray dried complex with suitable excipients showed 100 % dissolution within five minutes. Accelerated stability studies of mouth dissolving tablets carried out as per ICH guidelines revealed that the tablets were stable.Cilj rada bio je poboljšati topljivost i oslobađanje karvedilola stvaranjem ternarnog kompleksa s β-ciklodekstrinom i limunskom kiselinom i razvoj tableta topljivih u ustima. Takve tablete su napravljene s ciljem da se poboljša apsorpcija iz usta i izbjegne efekt prvog prolaza, što bi moglo imati za posljedicu poboljšanu bioraspoloživost. Testovi topljivosti pokazali su da β-ciklodekstrin i limunska kiselina stvaraju kompleks s karvedilolom i značajno povećavaju njegovu topljivost. Ternarna kompleksacija karvedilola s β-ciklodekstrinom i limunskom kiselinom provedena je fizičkim miješanjem, gnječenjem i sušenjem raspršivanjem. Pripravljeni kompleksi karakterizirani su infracrvenom spektroskopijom, diferencijalnom pretražnom kalorimetrijom, rendgenskom difraktometrijom praha, pretražnom elektronskom mikroskopijom i testovima učinkovitosti kompleksacije. Metodom sušenja raspršivanjem topljivost karvenidola povećala se 110 puta, a kompleksacija je bila najučinkovitija. Tablete pripravljene iz tog kompleksa i odgovarajućih pomoćnih tvari potpuno su se otopile unutar pet minuta. Testovi ubrzanog starenja provedeni prema ICH smjernicama pokazali su da su tablete stabilne

Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis in pancreatic ß-cells for effective management of type 1 diabetes mellitus

Background and Purpose: Approaches to prevent selective and progressive loss of insulin-producing ß-cells in Type 1 diabetes mellitus (T1DM) will help conquer this prevalent and devastating disease. Curcumin (CUR), a natural anti-inflammatory, suppresses diabetes associated inflammation and cell death. However, very high doses have been tested owing to poor oral bioavailability, making it difficult to translate to the clinic. Experimental approach: We recently prepared biodegradable nanosystems encapsulating curcumin (nCUR), resulting in at least 9-fold improvement in oral bioavailability. In the current study, we tested nCUR's ability to prevent streptozotocin (STZ)-induced inflammation and apoptosis in pancreatic islet/ß-cells. Key Results: Nonfasted rats pretreated with 10 or 50 mg/kg nCUR 6 hours prior to STZ challenge had up to 37% reduction in the glucose levels, while plain CUR (50 mg/kg) results in 12% reduction. This is owing to nCUR's ability to prevent islet/β-cell death evident from TUNEL assay, and H&E staining. Both CUR and nCUR significantly decreased levels of inflammatory cytokines in pancreatic tissue homogenates that correlated well with minimal histiocytic infiltration. The nCUR, rather than CUR pre-treatment prevented 8-oxo-2'-deoxyguanosine (8-oxo-dG), a sensitive biomarker of reactive oxygen species (ROS)-induced DNA damage in pancreas. Our data in normal rodents indicates that 28 days daily dosing with nCUR (25 to 100 mg/kg) did not cause any deleterious health issues by the carrier. Conclusions & Implications: Together, these data indicate a potentially translatable dose of nCUR that is safe and efficacious in improving the ß-cell function, possibly preventing T1DM