Dehydrodipeptide hydrogelators containing naproxen N‑Capped tryptophan: self-assembly, hydrogel characterization, and evaluation as potential drug nanocarriers

In this work, we introduce dipeptides containing tryptophan N-capped with the nonsteroidal anti-inflammatory drug naproxen and C-terminal dehydroamino acids, dehydrophenylalanine (ΔPhe), dehydroaminobutyric acid (ΔAbu), and dehydroalanine (ΔAla) as efficacious protease resistant hydrogelators. Optimized conditions for gel formation are reported. Transmission electron microscopy experiments revealed that the hydrogels consist of networks of micro/nanosized fibers formed by peptide self-assembly. Fluorescence and circular dichroism spectroscopy indicate that the self-assembly process is driven by stacking interactions of the aromatic groups. The naphthalene groups of the naproxen moieties are highly organized in the fibers through chiral stacking. Rheological experiments demonstrated that the most hydrophobic peptide (containing C-terminal ΔPhe) formed more elastic gels at lower critical gelation concentrations. This gel revealed irreversible breakup, while the C-terminal ΔAbu and ΔAla gels, although less elastic, exhibited structural recovery and partial healing of the elastic properties. A potential antitumor thieno[3,2-b]pyridine derivative was incorporated (noncovalently) into the gel formed by the hydrogelator containing C-terminal ΔPhe residue. Fluorescence and Förster resonance energy transfer measurements indicate that the drug is located in a hydrophobic environment, near/associated with the peptide fibers, establishing this type of hydrogel as a good drug-nanocarrier candidate.

Caught in the eye of the storm: a qualitative study of views and experiences of planned drug holidays from methylphenidate in child and adolescent ADHD treatment

Background: Attention deficit hyperactivity disorder (ADHD) can be treated with stimulant medication such as methylphenidate. Although effective, methylphenidate can cause serious side-effects, including suppressed appetite, growth retardation and sleep problems. A drug holiday is a deliberate interruption of pharmacotherapy for a defined period of time and for a specific clinical purpose, for example for appeasing side-effects. Whilst some international guidelines recommend introducing drug holidays in ADHD treatment, this is not practised routinely. Our aim was to examine the views and experiences of planned drug holidays from methylphenidate with adults who have responsibility for treatment decisions in children and adolescents with ADHD. Method: In-depth interviews were carried out. Child and Adolescent Mental Health Services (CAMHS) practitioners (n=8), General Practitioners (n=8), teachers (n=5), and mothers of children with ADHD (n=4) were interviewed in a UK setting. Interview transcripts were analysed using grounded theory. Results: Methylphenidate eases the experience of the child amid problems at home and at school and once started is mostly continued long-term. Some families do practise short-term drug holidays at weekends and longer-term ones during school holidays. The decision to introduce drug holidays is influenced by the child’s academic progress, the parents’ ability to cope with the child, as well as medication beliefs. Trialling a drug holiday is thought to allow older children to self-assess their ability to manage without medication when they show signs of wanting to discontinue treatment prematurely. Conclusions: Planned drug holidays could address premature treatment cessation by enabling adolescents to assess repercussions under medical supervision.

In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery

This study evaluated the use of Pluronic F127 and Pluronic F68 as excipients for formulating in situ gelling systems for ocular drug delivery. Thermal transitions have been studied in aqueous solutions of Pluronic F127, Pluronic F68 as well as their binary mixtures using differential scanning calorimetry, rheological measurements, and dynamic light scattering. It was established that the formation of transparent gels at physiologically relevant temperatures is observed only in the case of 20 wt % of Pluronic F127. The addition of Pluronic F68 to Pluronic F127 solutions increases the gelation temperature of binary formulation to above physiological range of temperatures. The biocompatibility evaluation of these formulations using slug mucosa irritation assay and bovine corneal erosion studies revealed that these polymers and their combinations do not cause significant irritation. In vitro drug retention study on glass surfaces and freshly excised bovine cornea showed superior performance of 20 wt % Pluronic F127 compared to other formulations. In addition, in vivo studies in rabbits demonstrated better retention performance of 20 wt % Pluronic F127 compared to Pluronic F68. These results confirmed that 20 wt % Pluronic F127 offers an attractive ocular formulation that can form a transparent gel in situ under physiological conditions with minimal irritation.

Mediated addiction: The drug discourses of Hong Kong youth

This paper examines the ways young people in Hong Kong at different stages of involvement with illegal drugs respond to government produced anti-drug television commercials through a methodology which provided them with the technical skills and equipment to make their own short videos about drugs. An analysis of the videos they produced and their interaction while producing them reveals that participants with different drug-taking experiences have very different and often multiple ways of talking about drugs, and that these different ‘discourses’ and the ways they are deployed in different contexts affect how ‘at-risk’ they are for new or continued drug use and how they respond to anti-drug messages designed to mitigate this risk.

Peptide based hydrogels for cancer drug release: modulation of stiffness, drug release and proteolytic stability of hydrogels by incorporating D-amino acid residue(s)

Synthetic tripeptide based noncytotoxic hydrogelators have been discovered for releasing an anticancer drug at physiological pH and temparature. Interestingly, gel stiffness, drug release capacity and proteolytic stability of these hydrogels have been successfully modulated by incorporating D-amino acid residues, indicating their potential use for drug delivery in the future.

Educating and motivating adolescents who are deaf or hard of hearing with drug and alcohol addiction: Components of a curriculum that links adolescents to appropriate treatment

This paper highlights the components necessary for a drug and alcohol addiction curricula to educate, motivate, and link adolescents who are deaf or hard of hearing using oral communication to appropriate treatment.

Experience With Lacosamide in a Series of Children With Drug-Resistant Focal Epilepsy

We report our pediatric experience with lacosarnide, a new antiepileptic drug, approved by the US Food and Drug Administration as adjunctive therapy in focal epilepsy in patients more than 17 years old. We retrospectively reviewed charts for lacosamide use and seizure frequency outcome in patients with focal epilepsy (Wilcoxon signed rank test). Sixteen patients (7 boys) were identified (median dose 275 mg daily, 4.7 mg/kg daily; mean age 14.9 years, range 8-21 years). Patients were receiving a median of 2 antiepileptic drugs (interquartile range [IQR] 1.7-3) in addition to having undergone previous epilepsy surgery (n = 3), vagus nerve stimulation (n = 9), and ketogenic diet (n = 3). Causes included structural (encephalomalacia and diffuse encephalitis, 1 each; stroke in 2) and genetic abnormalities (Aarskog and Rett syndromes, 1 each) or cause not known (n = 10). Median seizure frequency at baseline was 57 per month (IQR 7-75), and after a median follow-up of 4 months (range 1-13 months) of receiving lacosamide, it was 12.5 per month (IQR 3-75), (P < 0.01). Six patients (37.5%; 3 seizure free) were classified as having disease that responded to therapy (>= 50% reduction seizure frequency) and 10 as having disease that did not respond to therapy (<50% in 3; increase in 1; unchanged in 6). Adverse events (tics, behavioral disturbance, seizure worsening, and depression with suicidal ideation in 1 patient each) prompted lacosamide discontinuation in 4/16 (25%). This retrospective study of 16 children with drug-resistant focal epilepsy demonstrated good response to adjunctive lacosamide therapy (median seizure reduction of 39.6%; 37.5% with >= 50% seizure reduction) without severe adverse events. (C) 2011 Elsevier Inc. All rights reserved.

Higher evening antiepileptic drug dose for nocturnal and early-morning seizures

We describe 17 children with nocturnal or early-morning seizures who were switched to a proportionally higher evening dose of antiepileptic drugs and were retrospectively reviewed for seizure outcome and side effects. Of 10 children with unknown etiology, clinical presentation was consistent with nocturnal frontal lobe epilepsy (NFLE) in 5 and benign epilepsy with centrotemporal spikes (BECTS) in 3. After a mean follow-up of 5.3 months, 15 patients were classified as responders: 11 of these became seizure free (5 NFLE, 1 BECTS, 5 with structural lesions) and 4 (2 BECTS, 2 with structural lesions) experienced 75-90% reductions in seizures. Among two nonresponders, seizures in one had failed to resolve with epilepsy surgery. Nine subjects (53%) received monotherapy after dose modification, and none presented with worsening of seizures. Two complained of transient side effects (fatigue/somnolence). Differential dosing led to seizure freedom in 64.7% (11/17) of patients, and 88.2% (15/17) experienced >= 50% reductions in seizures. (C) 2010 Elsevier Inc. All rights reserved.