We outline a facile approach for the highly controlled and oriented coupling of antibody fragments to nanoparticles. We demonstrate the superior performance of these nanoparticles as targeted drug delivery vehicles versus a conventional formulation.
Interest in nanomedicines has grown rapidly over the past two decades, owing to the promising therapeutic applications they may provide, particularly for the treatment of cancer. Personalised medicine and ‘smart’ actively targeted nanoparticles represent an opportunity to deliver therapies directly to cancer cells and provide sustained drug release, in turn providing overall lower off-target toxicity and increased therapeutic efficacy. However, the successful translation of nanomedicines from encouraging pre-clinical findings to the clinic has, to date, proven arduous. In this review, we will discuss the use of nanomedicines for the treatment of cancer, with a specific focus on the use of polymeric and lipid nanoparticle delivery systems. In particular, we examine approaches exploring the surface functionalisation of nanomedicines to elicit active targeting and therapeutic effects as well as challenges and future directions for nanoparticles in cancer treatment.
The home parenteral nutrition (HPN) service at Cardiff and Vale NHS Trust is a rapidly expanding area with 34 patients currently being cared for. While every effort is made to prevent catheter-related infections (CRI) by means of rigorous training, strict line care and aseptic technique, it is inevitable that they do occur.The most effective means of eradication of such infections is removal of the colonised line. However, line removal carries drawbacks of its own, in particular, the risk of loosing vascular access.To avoid the need for line replacement, an intraluminal antibiotic lock may be used along with systemic intravenous antibiotics where in situ treatment is deemed acceptable. The evidence for using antibiotic line locks is sufficiently encouraging to justify their use.The local guideline at Cardiff and Vale is to use a 5 mg/ml vancomycin line lock together with peripheral systemic vancomycin. This treatment has been used successfully in salvaging lines in 10 episodes of CRI over a 2-year period.The National Patient Safety Agency (NPSA) promotes the safer use of injectable medicines and advocate ready-to-use preparations. In order to prepare the vancomycin 5 mg/ml line lock, a multiple dilution is necessary which when carried out at a ward level is in breach of NPSA guidelines (1) . A risk assessment of the process was carried out and a proposal for pharmacy aseptic services to prepare vancomycin 5 mg/ml line locks drawn up. It was proposed the pre-filled syringes would be kept as stock on the HPN specialist ward area.The syringes of vancomycin 5 mg/ml were given a 56-day shelf life when prepared in plastic syringes and stored in a refrigerator (2,3) . Having pre-filled vancomycin 5 mg/ml 3 ml syringes reduces manipulation at a ward level and so saves nursing time. The process is now NPSA compliant. As only one 500 mg vial of vancomycin is used to prepare a batch of 28 pre-filled syringes there is a cost saving compared with a vial being used for each dose when prepared on the ward.The introduction of vancomycin pre-prepared line locks has proved a useful, much appreciated and safer step to the treatment of CRI.
The adult multidisciplinary nutrition support team (NST) at the University Hospital of Wales (UHW) was funded in 1998 for inpatients requiring short-term parenteral nutrition (PN). Patients requiring home PN (HPN) were transferred to Intestinal Failure centres (IFC) for HPN training and/or specialised surgery. Development of the specialist expertise within the UHW NST led to a minority of patients being trained locally, a service that was subsequently commissioned by Health Commission Wales (HCW) in 2003. This is a summary of the activity of the adult HPN service at UHW to date.Since 2000, 49 patients (25 female, 24 male) have been referred to the UHW adult NST for HPN assessment and training (41 new patients) or ongoing care (8 established HPN). Of the 41 new referrals, 25 were inpatients (9 UHW; 13 local hospital; 3 IFC) and 16 were outpatients. The 8 established HPN patients were also outpatients. Thirty nine out of 41 patients were discharged on HPN. Two patients were not discharged home (1 died and 1 refused HPN). The main indication for HPN (70 %) is a result of multiple bowel resections (55 % of which Crohn's disease), bowel infarction (19 %) and altered GI motility (11 %).Overall, the mean age of patients at the start of HPN was 50.55 years, range 18-76 years. On discharge or transfer of care, 35 patients were self-caring, 7 dependent upon nursing support by home care company and 5 supported by their spouse/partner. The majority (45) patients were discharged to their own home, 1 to sheltered accommodation and 1 to residential care. Forty four patients were relatively independent and 3 housebound. Patients have received HPN for a mean of 4.1 years (range 1 week to 26 years).Since discharge or transfer of care, 7 patients have died (not HPN related) and 7 have stopped HPN (4 following reconstructive surgery, 1 patient request, 2 repeated infection) resulting in the current cohort of 33 patients. Three patients have gone from self-caring to needing nursing support. Mean age of current patients is 52.6 years, range 18-78 years.Referrals for HPN have dramatically increased in more recent years. During 2001-5, 1 to 2 patients were discharged annually, 6-7 per year 2006-7 and in excess of 10 per year, 2008-9. A further 3 patients are currently being trained for HPN. This is likely a combination of improved critical care medicine, surgical expertise, wound and stoma care in addition to PN and line care and an increased knowledge/ confidence in the local specialist service and an agreed commissioning model of service.
and 2 Calea WA7 1NT, UK Catheter occlusion is the second most common problem associated with vascular access devices (1) . In patients receiving parenteral nutrition (PN), lipid deposits can form a waxy substance along the lumen of the line which gradually occludes the central venous catheter (CVC) (2) . The use of 70 % ethanol locks has been reported to unblock lipid occlusions (3) ; while a 20 % ethanol flush after lipid infusions has been reported to help prevent the build-up of lipid deposits that occlude the CVC (4,5) .Endoluminal brushing of CVC's is more widely known for improving flow rates in catheters used for haemodialysis (5,6) . The FAS endoluminal brush has been used successfully to diagnose CVC related sepsis, while the line remains in situ (7)(8)(9) . In this study, the FAS endoluminal brush is used to salvage occluded CVC's used for long-term PN.A retrospective audit was done on all the patients receiving long-term PN over the preceding 4 years. Seventy six FAS endoluminal brushes were performed on 40 patient episodes of line occlusions over a 4-year period.
The prescribing of parenteral nutrition (PN) was identified as a problem in 2005 following an in house audit. In many cases PN was not being prescribed at all, in others it was being prescribed incorrectly. This had profound legal implications as PN, which is a prescription only medicine, was being compounded, supplied and administered where no legal prescription existed.Having identified a need to improve the prescribing of PN, the nutrition support team (NST) pharmacist secured funding to undertake the non-medical prescribing course. In order to complete the course, the pharmacist gained support from both the lead clinician for the NST, her pharmaceutical and NST colleagues.A 'PN prescription details' chart has been developed detailing the content of the PN. A programme of education and training is being carried out by the NST where the legal classification of PN, the need for a written prescription and the role of non-medical prescribing is highlighted.The pharmacist qualified as a non-medical prescriber in March 2008. Since then a clinical management plan has been developed for inpatients receiving PN. Although obtaining patient consent is not a problem with patients who are alert and mentally well, it causes difficulties in patients who are unwell. In these cases, consent is obtained at the earliest possible opportunity and in the meantime, working with the medical team overseeing the care of the patient, the PN is prescribed by the non-medical prescriber. In obtaining patient consent, the NST have found themselves undertaking a more active role in explaining to the patient the processes involved in receiving PN.Local audits have shown vast improvements in the prescribing of PN with almost 100% of PN now being prescribed correctly. A guideline in conjunction with the 'PN prescription details' chart has been submitted to the Cardiff and Vale NHS Trust for ratification and which may then be used by others in the absence of the non-medical prescriber.Written information is being developed to give to patients to explain the nature of non-medical prescribing and to be used as an aid to obtain patient consent.The prescribing of PN is now consistent and accurate following the implementation of non-medical prescribing. Having implemented this process patient care and record keeping has been improved.
Current evidence advocates filtering parenteral nutrition (PN) in patients who require prolonged parenteral therapy and the immunocompromised (1) . Almost all adult patients receiving parenteral nutrition at University Hospital Wales, Cardiff fall into either or both of these categories.In November 2007, a pilot study was carried out to investigate the possibility of adding giving sets and filters to PN infusion bags in pharmacy aseptic services (AS). The Pall TNA 2E 1.2 micron filters were used for all infusions. Although there were some minor problems, the study concluded this was a feasible option.In January 2008, the addition of giving sets and filters to adult PN infusion bags in pharmacy AS was made permanent. Three months after initiating the change, an audit revealed overall satisfaction was good. Minor problems were reported, namely, the weight of the filters on patients central lines and the packing of the PN in protect from light covers. One year later an audit revealed an overall satisfaction with amended practice as, again, good. Problems reported included a small number of nursing staff having difficulties priming the filter and the weight of the filter on the central and peripheral lines.
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