BACKGROUND: Chemotherapeutic drugs cause severe toxicities if administered unprotected, without proper targeting, and controlled release. In this study, we developed topotecan- (TPT-) loaded solid lipid nanoparticles (SLNs) for their chemotherapeutic effect against colorectal cancer. The TPT-SLNs were further incorporated into a thermoresponsive hydrogel system (TRHS) (TPT-SLNs-TRHS) to ensure control release and reduce toxicity of the drug. Microemulsion technique and cold method were, respectively, used to develop TPT-SLNs and TPT-SLNs-TRHS. Particle size, polydispersive index (PDI), and incorporation efficiency (IE) of the TPT-SLNs were determined. Similarly, gelation time, gel strength, and bioadhesive force studies of the TPT-SLNs-TRHS were performed. Additionally, in vitro release and pharmacokinetic and antitumour evaluations of the formulation were done. RESULTS: TPT-SLNs have uniformly distributed particles with mean size in nanorange (174 nm) and IE of ~90%. TPT-SLNs-TRHS demonstrated suitable gelation properties upon administration into the rat's rectum. Moreover, drug release was exhibited in a control manner over an extended period of time for the incorporated TPT. Pharmacokinetic studies showed enhanced bioavailability of the TPT with improved plasma concentration and AUC. Further, it showed significantly enhanced antitumour effect in tumour-bearing mice as compared to the test formulations. CONCLUSION: It can be concluded that SLNs incorporated in TRHS could be a potential source of the antitumour drug delivery with better control of the drug release and no toxicity.
Colorectal Neoplasms/drug therapy , Drug Delivery Systems , Hydrogels/chemistry , Lipids/chemistry , Macromolecular Substances/chemistry , Nanoparticles/chemistry , Temperature , Topotecan/therapeutic use , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Death/drug effects , Cell Line, Tumor , Female , Humans , Male , Mice, Nude , Mucous Membrane/drug effects , Mucous Membrane/pathology , Nanoparticles/ultrastructure , Particle Size , Rats, Sprague-Dawley , Rectum/drug effects , Rectum/pathology , Topotecan/blood , Topotecan/pharmacokinetics , Topotecan/pharmacology
BACKGROUND: Unfractionated heparin has been traditionally used for anticoagulation during hemodialysis (HD), but more recently low-molecular-weight heparin (LMWH) is being used as an alternative. Anti-Xa activity can be measured as a surrogate of LMWH efficacy. We present 52 patients treated with tinzaparin anticoagulation on HD, confirming that fixed dosing is safe and efficacious with sound pharmacodynamic reason in relation to anti-Xa profiling. METHODS: We undertook a prospective audit in a single dialysis unit. All patients were established on a simple anticoagulation protocol for at least 1 month prior to the audit. Blood anti-Xa activity was measured at time 0, 30, 60 and 120 min into and at the end of HD. Efficacy and safety data were collected on the study day and the two sessions before and after it. RESULTS: Fifty-two patients were included in the efficacy and safety analysis with 43 patients undergoing anti-Xa analysis (9 sampling errors). Using current consensus (an end-HD anti-Xa activity of <0.4 IU/ml), our fixed-dose protocol resulted in satisfactory safety in all patients tested. Of 260 HD sessions, 10 (4%) had reduced tinzaparin efficacy. During 105 dialysis sessions (21 patients) using an arteriovenous fistula, 4 patients had one episode of minor bleeding and there were 6 episodes (2 patients) of post-needle-compression time greater than 15 min. CONCLUSION: Tinzaparin administered thrice weekly as a fixed dose has good efficacy and is well tolerated as an anticoagulant during HD when used according to our protocol.
Algorithms , Factor Xa/analysis , Heparin, Low-Molecular-Weight/administration & dosage , Heparin, Low-Molecular-Weight/blood , Renal Dialysis/adverse effects , Thrombosis/etiology , Thrombosis/prevention & control , Adult , Aged , Aged, 80 and over , Anticoagulants/administration & dosage , Dose-Response Relationship, Drug , Drug Monitoring/methods , Female , Fibrinolytic Agents/administration & dosage , Humans , Male , Middle Aged , Thrombosis/blood , Tinzaparin , Treatment Outcome
The clinical presentation of perianal abscesses due to foreign bodies (FBs) impacted in the anal canal mimics common causes of acute anal pain. The diagnosis can be established by digital rectal examination and/or proctoscopy, but may miss the presence of an FB. Incision and drainage of the abscess, along with removal of the FB, results in immediate pain relief and cure. Impacted FB must not be overlooked as an unusual cause of perianal abscess. One case of perianal abscesses due to FB impacted in the anal canal is reported.
We present a transport model for molecular conduction involving an extended Hückel theoretical treatment of the molecular chemistry combined with a nonequilibrium Green's function treatment of quantum transport. The self-consistent potential is approximated by CNDO (complete neglect of differential overlap) method and the electrostatic effects of metallic leads (bias and image charges) are included through a three-dimensional finite element method. This allows us to capture spatial details of the electrostatic potential profile, including effects of charging, screening, and complicated electrode configurations employing only a single adjustable parameter to locate the Fermi energy. As this model is based on semiempirical methods it is computationally inexpensive and flexible compared to ab initio models, yet at the same time it is able to capture salient qualitative features as well as several relevant quantitative details of transport. We apply our model to investigate recent experimental data on alkane dithiol molecules obtained in a nanopore setup. We also present a comparison study of single molecule transistors and identify electronic properties that control their performance.
