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.
BackgroundNegative-pressure wound therapy is a technique to achieve wound healing in patients with non-healing wounds of the lower limb; vacuum-assisted closure (VAC) therapy is a technique to accelerate the healing of non-healing ulcers that fail to heal on their own (primary healing) (Plast Reconstr Surg 117:193–209S, 2006).Delayed wound healing or non-healing of ulcers is a significant health problem, particularly in older adults.The efficacy of VAC dressings has been demonstrated in several randomized controlled studies, which have shown significantly faster wound healing rates compared to conventional wound therapy (Lancet 366:1704–10, 2005; J Wound Care 17:426–32, 2008). However, commercially available VAC is costly.The aim of using custom made VAC was decided by our team due to lower socio-economic status of patients taken for study who could not have afforded charges of commercially available VAC unit.ObjectiveObjective was to evaluate VAC therapy compared with conventional dressings in the treatment of non-healing lower limb ulcers in lower socio-economic patients.MethodsSixty patients of lower socio-economic status aged between 40 and 70 were prospectively studied for non-healing ulcers Wagner grade 2 or 3 and randomized into 2 groups. VAC dressing was kept for over a period of 2–7 weeks. Ulcers were treated until the wound closed spontaneously, surgically or until completion of the 50-day period, whichever was earlier.ResultsBy seventh week, discharge disappeared in 96 % in VAC and only 54 % in conventional dressing group.Granulation tissue appeared in 100 % of patients in VAC group and only 63 % in conventional dressing group. The patients treated with VAC dressing in our study showed comparable wound reduction capabilities with an average wound size reduction of 56 % in comparison to conventional dressing group which had average wound size reduction of 29 %.Majority of wounds in VAC group got closed in 7 weeks. Patient satisfaction was excellent in the majority of patients in VAC group compared to those in conventional dressing group.ConclusionThe application of VAC™ had shown good results in our study.
Background The purpose of this study was to investigate the suitability of nanostructured lipid carriers (NLCs) loaded with miltefosine (HePC) as an anticancer drug for the treatment of breast cancer. Methods HePC-NLCs were prepared using a microemulsion technique and then evaluated for particle size, polydispersity index (PDI), incorporation efficiency, in vitro release of entrapped drug, and hemolytic potential. Furthermore, pharmacokinetic, biodistribution, and liver toxicity analyses were performed in Sprague–Dawley rats, and antitumor efficacy was evaluated in Michigan Cancer Foundation-7 (MCF-7) and squamous cell carcinoma-7 (SCC-7) cells in vitro and in tumour-bearing BALB/c mice in vivo. Advanced analyses including survival rate, immunohistopathology, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays were performed to evaluate apoptosis in vivo. Results The average particle size of the HePC-NLCs was 143 ± 16 nm, with a narrow PDI (0.104 ± 0.002), and the incorporation efficiency was found to be 91 ± 7%. The NLCs released HePC in a sustained manner, and this release was significantly lower than that of free drug. The in vitro hemolytic assay demonstrated a significantly reduced hemolytic potential (~9%) of the NLCs compared to that of the test formulations. The HePC-NLCs demonstrated enhanced pharmacokinetic behaviour over free drug, including extended blood circulation and an abridged clearance rate in rats. Furthermore, the HePC-NLCs exhibited higher cytotoxicity than the free drug in MCF-7 and SCC-7 cells. Moreover, the HePC-NLCs showed significantly enhanced ( P < 0.005) antitumor activity compared to that of the control and free drug-treated mouse groups. Tumour cell apoptosis was also confirmed, indicating the antitumor potential of the HePC-NLCs. Conclusion These findings demonstrate the ability of NLCs as a drug delivery system for enhanced pharmacokinetic, antitumor, and apoptotic effects, most importantly when loaded with HePC.
Hepatitis C virus (HCV) quantification is used as a prognostic marker for treatment success. In a routine clinical laboratory some infinitesimal sample handling factors can contribute to variability and loss of precision in HCV quantification. This may include blood collection tubes, blood drawing procedure, sample processing and storage temperatures. In current study blood was collected in tubes with different anticoagulant type (spray vs. liquid), group 1, blood was drawn with possible suck of methylated spirit through needle (experimental group) while avoiding the methylated spirit suck (control group) group 2, plasma separation was delayed from 0 to 60 min for group 3, plasma storage at different temperatures group 4. All samples were analyzed using Corbett research real time PCR system using AJ Roboscreen Kit. Mean viral load difference between spray vs. liquid was found 3.6 × 10(5) IU/ml (p < 0.001). Methylated spirit inhibited the viral load quantification with a value of 4.8 × 10(5) IU/ml (p < 0.001). Mean viral load difference was found 1.2 × 10(5) IU/ml (p < 0.05). Delay in centrifugation from 0 to 60 min and plasma placement at 25 °C for 15 min before freezing had no effect (p = 0.5996). Plasma storage temperature at -80 and -20 °C did not affect significantly on RNA levels (p > 0.05). In conclusion blood collection tubes and procedures can be a key factor in variability of results, that might affect the treatment response decision.
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