Effect of different carboxylic acids in cyclodextrin functionalization of cellulose nanocrystals for prolonged release of carvacrol.

Current investigations deal with new surface functionalization strategy of nanocrystalline cellulose-based substrates to impart active molecule release properties. In this study, cellulose nanocrystals (CNC) were surface-functionalized with ß-cyclodextrin (ß-CD) using succinic acid (SA) and fumaric acid (FA) as bridging agents. The main objective of this surface modification performed only in aqueous media was to obtain new active materials able to release antibacterial molecules over a prolonged period of time. The reactions were conducted by immersing the CNC film into a solution composed of ß-CD, SA and FA, leading to CNC grafting. The materials were characterized by infrared spectroscopy (FT-IR), Quartz crystal microbalance-dissipation (QCM-D), AFM and phenolphthalein (PhP) was used to determine the efficiency of CNC grafting with ß-CD. The results indicated that ß-CD was successfully attached to the CNC backbone through the formation of ester bonds. Furthermore, carvacrol was entrapped by the attached ß-CD and a prolonged release was confirmed. In particular, CNC grafted to ß-CD in the presence of FA was selected as the best solution. The antibacterial activity and the controlled release were studied for this sample. Considerably longer bacterial activity against B. subtilis was observed for CNC grafted to ß-CD compared to CNC and CNC-FA, confirming the promising impact of the present strategy.

Reducing pre-operative fasting while preserving operating room scheduling flexibility: feasibility and impact on patient discomfort.

BACKGROUND: The need to preserve operating room (OR) scheduling flexibility can challenge adherence to the 2-h pre-operative fasting period recommendation before elective surgery. Our primary objective was to assess the feasibility of a pre-operative carbohydrate (CHO) drink delivery strategy preserving OR scheduling flexibility. METHODS: During the 1st study phase, patients admitted for elective surgery fasted overnight (Control group); during the 2nd phase, patients fasted overnight and received a pre-operative CHO drink (CHO group). CHO delivery time was set to allow any patient to be ready for surgery 30 min ahead of the scheduled time and any patient with an operation scheduled in the afternoon to be ready at 13:00 hours; patients admitted the morning of an early morning operation would not be allowed to take a CHO drink. RESULTS: We included 194 patients in the Control group and 199 in the CHO group. In the CHO group, the morning CHO dose was delivered to 66.3% of the patients (95% CI 59.3-72.9%), with a median pre-operative fasting time period of 4 h 57 min. After excluding patients admitted the morning of an operation scheduled before 10:00 hours, the delivery rate was 77.2% (70.2-83.3%). Patients in the CHO group experienced significantly less pre-operative thirst (median 2 vs. 5 on a 0-10 scale, P < 0.0001) and hunger (0 vs. 2, P < 0.0001) than those in the Control group. CONCLUSION: Although preservation of OR scheduling flexibility resulted in a longer fasting time than recommended, CHO drink can be made available to a large proportion of patients with significantly reduced perioperative discomfort.

Porous silicon-cyclodextrin based polymer composites for drug delivery applications.

One of the main applications of porous silicon (PSi) in biomedicine is drug release, either as a single material or as a part of a composite. PSi composites are attractive candidates for drug delivery systems because they can display new chemical and physical characteristics, which are not exhibited by the individual constituents alone. Since cyclodextrin-based polymers have been proven efficient materials for drug delivery, in this work ß-cyclodextrin-citric acid in-situ polymerization was used to functionalize two kinds of PSi (nanoporous and macroporous). The synthesized composites were characterized by microscopy techniques (SEM and AFM), physicochemical methods (ATR-FTIR, XPS, water contact angle, TGA and TBO titration) and a preliminary biological assay was performed. Both systems were tested as drug delivery platforms with two different model drugs, namely, ciprofloxacin (an antibiotic) and prednisolone (an anti-inflammatory), in two different media: pure water and PBS solution. Results show that both kinds of PSi/ß-cyclodextrin-citric acid polymer composites, nano- and macro-, provide enhanced release control for drug delivery applications than non-functionalized PSi samples.

Poly-(cyclo)dextrins as ethoxzolamide carriers in ophthalmic solutions and in contact lenses.

Efficient ophthalmic therapy requires the development of strategies that can provide sufficiently high drug levels in the ocular structures for a prolonged time. This work focuses on the suitability of poly-(cyclo)dextrins as carriers able to solubilize the carbonic anhydrase inhibitor (CAI) ethoxzolamide (ETOX), which is so far used for oral treatment of glaucoma. Topical ocular treatment should notably enhance the efficiency/safety profile of the drug. Natural α-, ß- and γ-cyclodextrins and a maltodextrin were separately polymerized using citric acid as cross-linker agent under mild conditions. The resultant hydrophilic polymers exhibited larger capability to solubilize ETOX than the pristine (cyclo)dextrins. Moreover, they provided sustained drug diffusion in artificial lachrymal fluid. Interestingly the poly-(cyclo)dextrins solutions facilitate the loading of remarkably high doses of ETOX in poly(2-hydroxyethyl methacrylate)-based contact lenses. Exploiting ionic interactions between functional groups in the contact lenses and remnant free carboxylic acids in the citric acid linkers of poly-(cyclo)dextrins led to the retention of the drug-loaded poly-(cyclo)dextrins and, in turn, to sustained release for several weeks.

Comparative study of vascular prostheses coated with polycyclodextrins for controlled ciprofloxacin release.

A textile polyester vascular graft was modified with cyclodextrins to obtain a new implant capable of releasing antibiotics (here ciprofloxacin, CFX) over prolonged time periods and thereby reducing the risk of post-operative infections. In this study, we compared samples modified with native and modified cyclodextrins, presenting different cavity sizes (ß or γ cyclodextrins) and different substituent groups (hydroxypropyl and methyl). Drug release was measured in water, phosphate buffer pH 7.4 and blood plasma. The inclusion of CFX in the cyclodextrins cavities was observed in solution by two-dimensional (1)H NMR spectroscopy and confirmed by (1)F NMR measurements. Grafts modification with all cyclodextrins induced an increase of their sorption capacity towards CFX whose extent depended on the nature of the cyclodextrin: a 4-fold and 10-fold increase was observed in the cases of hydroxypropyl cyclodextrins and methylated ß-cyclodextrin, respectively. Depending on the type of release medium and nature of CD, different CFX release kinetics were obtained. The discussion highlighted not only the role of the host guest complexation, but also that of the electrostatic interactions that occur between the anionic crosslinks of the cyclodextrins polymers, and CFX that presents a zwitterionic character. The microbiological assessment confirmed sustained CFX release in human plasma and demonstrated antibacterial efficiency of CD modified prostheses against Staphylococcus aureus and Escherichia coli for at least 24 h (compared to 4 h in the case of virgin grafts).

Methyl-ß-cyclodextrin modified vascular prosthesis: Influence of the modification level on the drug delivery properties in different media.

A textile polyester vascular graft was modified with methyl-ß-cyclodextrin (MeßCD) to obtain a new implant capable of releasing antibiotics directly in situ at the site of operation over a prolonged period and thereby prevent post-operative infections. We investigated the influence of the curing parameters (time and temperature) that allow control of the degree of functionalization (DF) of the support by MeßCD. The inclusion of ciprofloxacin (CFX) in the MeßCD cavity was observed in solution by two-dimensional (1)H NMR spectroscopy. The amount of CFX loaded on the modified graft increased with DF. Depending on the release medium (water, phosphate-buffered saline, or human plasma) and the DF of the prostheses, different kinetic profiles of release of CFX were obtained. The sustained release of CFX in human plasma was shown by microbiological assays that indicated prolonged antimicrobial activity against Staphylococcus aureus and Escherichia coli. Viability tests demonstrated the non-toxicity of MeßCD to an epithelial cell line (HPMEC), although a decrease in endothelial cell number was observed on the functionalized prosthesis, probably due to the roughness of the coating and also to the nature of the MeßCD polymer present on the surface of the fibers.

Laparoscopically assisted Hartman's reversal is an efficacious and efficient procedure: a case control study.

AIM: Laparoscopy may lower the mortality and morbidity rates of Hartmann's procedure reversal. However, it remains a challenging operation mainly due to adhesions of the small bowel and to the rectal stump. METHODS: We performed a retrospective review of 44 patients who had laparoscopic Hartmann's reversal (Group A). On a case-control basis, these patients were compared to 44 patients (Group B) who had open Hartmann's reversal. RESULTS: Preoperative patients' characteristics (sex, gender, BMI, ASA status, prior surgery, comorbidities, colonic disease) were comparable. Conversion rate in Group A was 9.1%. Operative incidents were comparable in both groups. Operative duration was not significantly shorter in Group B (195 min versus 160 min in Group B). Mortality rate was 2.2 % and O % in group A and B, respectively. Overall morbidity rate was 11.4 % and 28.6 % in Group A and B, respectively (P<0.05). The mean length of hospital stay was significantly shorter in Group A (4.8 days) as compared to Group B (6.8 days), respectively. An efficiency analysis was performed and demonstrated that laparoscopic reversal did not generate a significant additional cost. CONCLUSION: Our laparoscopic technique of Hartmann's procedure reversal is safe and efficient. It compares positively with the same procedure performed openly in a case control study. Moreover, an indirect cost reduction is generated by the reduction of the length of hospital stay.

[Impossible withdrawal of an epidural catheter]. / Retrait impossible d'un cathéter de péridural.

The knotting of an epidural catheter is a rare complication preventing catheter withdrawal. We report two cases of catheter knotting and subsequent impossible withdrawal with moderate repeated traction. Imaging by CT scan allowed visualisation in the epidural space of a loop and a real knot for the first and the second patient respectively. The common risk factor found was an excess in catheter length inserted. A surgical procedure was necessary for both patients.

Functionalization of PVDF membranes with carbohydrate derivates for the controlled delivery of chlorhexidin.

Maltodextrin (MX) was fixed onto PVDF membranes in order to create a drug delivery Guided Tissue Regeneration (GTR) device with controlled drug delivery properties. PVDF microporous membranes were treated by a mixture of MX and citric acid, resulting to an 18 wt% increase of the supports. MX grafted membrane could capture 103 mg/g chlorhexidin digluconate (DigCHX) instead of 1mg/g for a virgin membrane. A neutralization step was performed before the biological tests. Viability tests confirmed the non-toxicity of the MX polymer coating after neutralisation. In vitro release test in human plasma, and microbiological tests showed that membranes grafted with MX were more performing compared to virgin and beta-CD grafted membranes. The antimicrobial activity was effective during more than 72 h.