Designed sponges based on chitosan and cyclodextrin polymer for a local release of ciprofloxacin in diabetic foot infections.

Diabetic foot infections are the most common complications requiring hospitalisation of patients with diabetes. They often result in amputation to extremities and are associated with high morbi-mortality rates, especially when bone is infected. Treatment of these complications is based on surgical procedures, nursing care and systemic antibiotic therapy for several weeks, with a significant risk of relapse. Due to low blood flow and damage caused by diabetic foot infection, blood supply is decreased, causing low antibiotic diffusion in the infected site and an increase of possible bacterial resistance, making this type of infection particularly difficult to treat. In this context, the aim of this work was to develop a medical device for local antibiotic release. The device is a lyophilized physical hydrogel, i.e a sponge based on two oppositely charged polyelectrolytes (chitosan and poly(cyclodextrin citrate)). Cyclodextrins, via inclusion complexes, increase drug bioavailability and allow an extended release. Using local release administration increases concentrations in the wound without risk of toxicity to the body and prevents the emergence of resistant bacteria. The hydrogel was characterised by rheology. After freeze-drying, a curing process was implemented. The swelling rate and cell viability were evaluated, and finally, the sponge was impregnated with a ciprofloxacin solution to evaluate its drug release profile and its antibacterial activity.

[Pharmaceutical system of fecal microbiota transplantation: Heterogeneous practices]. / Circuit pharmaceutique, transplantation de microbiote fécal : Des pratiques hétérogènes.

OBJECTIVE: To describe current pharmaceutical practice in French hospitals regarding fecal microbiota transplantation in terms of prescription, preparation and compounding, as well as local legislation. MATERIAL AND METHODS: A national survey was conducted at 28 French university hospital centers followed by the sending of a GoogleForm® questionnaire from June to August 2018 in the 16 respondent centers either performing or subcontracting fecal microbiota transplant. RESULTS: All hospitals performing or subcontracting fecal transplant (n=16,%57) report prescription indication of recurrent Clostridium difficile infection treatment, and 6 of them also as part of a clinical trial protocol. In hospitals performing fecal transplant themselves (n=11), the number of pre-donation consultations with donors varies from one (n=6) to two (n=5). Fecal sample is collected at the donor's home in 45% of cases. Route of administration for transplant is either naso-gastric administration (n=4), rectal (n=4) or both (n=5). Fecal samples for transplant are compounded either in the hospital pharmacy (n=73%) or in the laboratory (27%). Thawing methods include refrigeration between 2-8°C (50%), room temperature (25%) and water bath (25%). Billing system and reporting to health authorities are highly heterogeneous from one hospital to another. CONCLUSION: This survey shows significant pharmaceutical practice heterogeneity within French hospitals regarding fecal microbiota transplantation despite the existence of national and European recommendations.

Hypochlorous acid is antipruritic and anti-inflammatory in a mouse model of atopic dermatitis.

BACKGROUND: It has been reported that topical hypochlorous acid (HOCl) formulations lead to relief of itch in human patients with atopic dermatitis; however, the specific antipruritic mechanism of action remains unclear. OBJECTIVE: To confirm itch relief and reduction of lesions in a mouse model of atopic dermatitis and to elucidate possible HOCl's mode of action. METHODS: In this study, the effects of topical administration of HOCl hydrogel (0.05%) on atopic dermatitis-like lesions in NC/Nga mice model as well as in vitro effects of HOCl on dorsal root ganglia neurons and mouse bone marrow-derived dendritic cells (mBMDCs) were investigated. NC/Nga mice were sensitized with house dust mite allergen and treated topically with HOCl hydrogel both preventively and therapeutically against established lesions. Allergen challenge was continued during HOCl hydrogel application. RESULTS: Treatment with HOCl hydrogel prevented the development of lesions and scratching bouts during the whole observation period. When administered after full development of lesions, HOCl reduced lesions and scratching behaviour to a similar extent as a positive control 0.1% betamethasone dipropionate ointment. The reduced inflammatory response by HOCl treatment was demonstrated by reduced secretion of inflammatory cytokines in affected skin tissue from NC/Nga mice. In addition, HOCl significantly reduced IL-12 production in mBMDC. The diminished scratching behaviour was confirmed by impaired response to several pruritogens in dorsal root ganglia neurons excised from NC/Nga mice after termination of the studies. The response to the stimuli was also reduced by pre-incubation of sensory neurons from untreated BALB/c mice with 0.0001% HOCl. CONCLUSIONS AND CLINICAL RELEVANCE: These data indicate a direct reduction in sensory response by HOCl, leading to significantly reduced itch and inflammation in vivo.

Computational Study of the Binding Modes of Diverse DPN Analogues on Estrogen Receptors (ER) and the Biological Evaluation of a New Potential Antiestrogenic Ligand.

Estrogen (17ß-estradiol) is essential for normal growth and differentiation in the mammary gland. In the last three decades, previous investigations have revealed that Estrogen Receptor Alpha (ERα) plays a critical role in breast cancer. More recently, observations regarding the widespread expression of ERß-like proteins in normal and neoplastic mammary tissues have suggested that ERß is also involved in the mentioned pathology. Design of new drugs both steroidal and nonsteroidal that target any of these receptors represents a promise to treat breast cancer although it remains a challenge due to the sequence similarity between their catalytic domains. In this work, we propose a new set of compounds that could effectively target the estrogen receptors ERα and ERß. These ligands were designed based on the chemical structure of the ERß-selective agonist Diarylpropionitrile (DPN). The designed ligands were submitted to in silico ADMET studies, yielding in a filtered list of ligands that showed better drug-like properties. Molecular dynamics simulations of both estrogen receptors and docking analysis were carried-out employing the designed compounds, from which two were chosen due to their promising characteristics retrieved from theoretical results (docking analysis or targeting receptor predictions). They were chemically synthetized and during the process, two precursor ligands were also obtained. These four ligands were subjected to biological studies from which it could be detected that compound mol60b dislplayed inhibitory activity and its ability to activate the transcription via an estrogenic mechanism of action was also determined. Interestinly, this observation can be related to theoretical binding free energy calculations, where the complex: ERß-mol60b showed the highest energy ΔGbind value in comparison to others.

Cyclodextrin modified PLLA parietal reinforcement implant with prolonged antibacterial activity.

The use of textile meshes in hernia repair is widespread in visceral surgery. Though, mesh infection is a complication that may prolong the patient recovery period and consequently presents an impact on public health economy. Such concern can be avoided thanks to a local and extended antibiotic release on the operative site. In recent developments, poly-l-lactic acid (PLLA) has been used in complement of polyethyleneterephthalate (Dacron®) (PET) or polypropylene (PP) yarns in the manufacture of semi-resorbable parietal implants. The goal of the present study consisted in assigning drug reservoir properties and prolonged antibacterial effect to a 100% PLLA knit through its functionalization with a cyclodextrin polymer (polyCD) and activation with ciprofloxacin. The study focused i) on the control of degree of polyCD functionalization of the PLLA support and on its physical and biological characterization by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC) and cell viability, ii) on the understanding of drug/meshes interaction using mathematic model and iii) on the correlation between drug release studies in phosphate buffer saline (PBS) and microbiological evaluation of meshes and release medium against E. coli and S. aureus. All above mentioned tests highlighted the contribution of polyCD on the improved performances of the resulting antibacterial implantable material. STATEMENT OF SIGNIFICANCE: 1. We managed for the first time, with well-defined parameters in terms of temperature and time of treatment, to functionalize a bio-absorbable synthetic material to improve drug sorption and drug release properties without affecting its mechanical properties. 2. We analyzed for the first time the degradation of our coating products by mass spectroscopy to show that only citrate and cyclodextrin residues (and glucose units) without any cytotoxicity are formed. 3. We managed to improve the mechanical properties of the PLA with the cyclodextrin polymer to form a composite. The assembly (cyclodextrin polymer and PLLA) remains biodegradable.

The immunoglobulin superfamily member CD200R identifies cells involved in type 2 immune responses.

BACKGROUND: The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL-4, IL-5, and IL-13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim of this investigation was to identify surface markers associated with type 2 inflammation. METHODS: Naïve human CD4+ T cells were short-term activated in the presence or absence of IL-4 and analyzed for expression of >300 cell-surface proteins. Ex vivo-isolated peripheral blood mononuclear cells (PBMCs) from peanut-allergic (PA) and nonallergic subjects were stimulated (14-16 h) with peanut extract to detect peanut-specific CD4+ CD154+ T cells. Biopsies were obtained for transcriptomic analysis from healthy controls and patients with extrinsic or intrinsic atopic dermatitis (AD) and psoriasis. RESULTS: Expression analysis of >300 surface proteins enabled identification of IL-4-upregulated surface proteins, such as CD90, CD108, CD109, and CD200R (CD200R1). Additional analysis of in vitro-differentiated Th0, Th1, and Th2 cultures identified CD200R as upregulated on Th2 cells. From ex vivo-isolated PBMCs, we found high expression of CD200R on Th2 and ILC2 cells and basophils. In PA subjects, the peanut-specific Th2 (CD154+ CRTh2+ ) cells expressed more CD200R than the non-allergen-specific Th2 (CD154- CRTh2+ ) cells. Moreover, costaining of CD161 and CD200R identified peanut-specific highly differentiated IL-4+ IL-5+ Th2 cells. Finally, transcriptomic analysis revealed upregulation of CD200R in lesional skin from subjects with an extrinsic AD phenotype compared to healthy skin. CONCLUSION: These results indicate that CD200R expression strongly correlates with Th2 pathology; though, the mechanism is as yet elusive.

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.

Human Atopic Dermatitis Skin-derived T Cells can Induce a Reaction in Mouse Keratinocytes in vivo.

In atopic dermatitis (AD), the inflammatory response between skin-infiltrating T cells and keratinocytes is fundamental to the development of chronic lesional eczema. The aim of this study was to investigate whether skin-derived T cells from AD patients could induce an inflammatory response in mice through keratinocyte activation and consequently cause the development of eczematous lesions. Punch biopsies of the lesional skin from AD patients were used to establish skin-derived T cell cultures, which were transferred to NOD.Cg-Prkd(scid) Il2rg(tm1Sug) /JicTac (NOG) mice. We found that the subcutaneous injection of the human AD skin-derived T cells resulted in the migration of the human T cells from subcutis to the papillary dermis followed by the development of erythema and oedema in the mouse skin. Furthermore, the human T cells induced a transient proliferative response in the mouse keratinocytes shown as increased numbers of Ki-67(+) keratinocytes and increased epidermal thickness. Out of six established AD skin-derived T cell cultures, two were superior at inducing a skin reaction in the mice, and these cultures were found to contain >10% CCR10(+) T cells compared to <2% for the other cultures. In comparison, blood-derived in vitro-differentiated Th2 cells only induced a weak response in a few of the mice. Thus, we conclude that human AD skin-derived T cells can induce a reaction in the mouse skin through the induction of a proliferative response in the mouse keratinocytes.

Visceral mesh modified with cyclodextrin for the local sustained delivery of ropivacaine.

The aim of the study was to develop a polyester visceral implant modified with a cyclodextrin polymer for the local and prolonged delivery of ropivacaine to reduce post operatory pain. Therefore, we applied a coating of an inguinal mesh with a crosslinked polymer of hydroxypropyl-ß-cyclodextrin (HPßCD) whose specific host-guest complex forming properties were expected to improve the adsorption capacity of the implant toward anesthetic, and then to release it within a sustained period. The modification reaction of the textile with cyclodextrin was explored through the study of the influence of the pad/dry/cure process parameters and the resulting implant (PET-CD) was characterized by solid state NMR and SEM. Besides, the inclusion complex between ropivacaine and CD was studied by NMR and capillary electrophoresis in PBS medium. Finally, ropivacaine sorption test showed that a maximum of 30 mg/g of ropivacaine could be adsorbed on the functionalized samples. In dynamic batch tests in PBS at pH 7.4, the release could be observed up to 6h. The cytocompatibility of the PET-CD loaded with ropivacaine was also studied and reached 65% cell vitality after 6 days.

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.

Dyeing and antibacterial activation with methylene blue of a cyclodextrin modified polyester vascular graft.

The aim of this study was to develop an antiseptic and blue dyed polyester (PET) vascular graft in order to reach two distinct properties: (i) the prevention of postoperative infections, (ii) the improvement of the graft compatibility with the coelioscopy surgical technique. This work consisted of dyeing a vascular prosthesis with methylene blue (MB) which is known as a cationic dye with antiseptic properties. Therefore, the functionalization of the PET fibers of the prosthesis with a cyclodextrin-citric acid polymer (PolyCD) was achieved in order to improve its sorption capacity. The NMR experiments demonstrated that a 1:2 complex occurred between hydroxypropyl ß-cyclodextrin (HP-ßCD) and MB. Kinetic and sorption isotherm studies showed that an impregnation of the polyCD modified prosthesis (PET-CD) in a 1 g L(-1) of MB solution for 150 min was sufficient to reach the saturation of the device. Results proved that the adsorption mechanism followed the Langmuir model and a maximum of 20 mg g(-1) of MB on the graft. A sustained release of MB in batch tests was observed in PBS and in vitro microbiological assays displayed a prolongation of the bactericidal effect of PET-CD whose extent varied with the amount of MB preliminarily adsorbed onto the PET-CD.

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.

Validating the poly-cyclodextrins based local drug delivery system on plasma-sprayed hydroxyapatite coated orthopedic implant with toluidine blue O.

Local antibiotics delivery is an efficient solution to reduce the risk of infections associated with orthopedic implant. This study aims to functionalize plasma-sprayed hydroxyapatite coated titanium (Ti-HA) hip joint implant material with cyclodextrins-polymer (polyCD)-based local drug delivery system for loading therapeutic molecules (e.g. antibiotics), to offer a sustainable drug delivery. The process of polyCD coating on Ti-HA material was optimized with the help of model guest molecule - toluidine blue O (TBO) for evaluating the efficacy of polyCD system. The obtained results clearly showed that polyCD's treatment can firmly coat on the Ti-HA material under the optimized processing parameters concerning the type of CD, thermal treatment temperature and duration. PolyCD system has been proven to have a high capacity of TBO adsorption and long release duration. In vitro study also showed non-cytotoxicity of polyCD functionalized samples to osteoblastic cells. Trial study with gentamicin revealed very promising potential of polyCD system for sustained delivery of antibiotics. To conclude, the study substantiates the prospective flexibility of drug choice when applying polyCD treated implants including antibiotics, antimitotic agents or other therapeutical molecules. One or more drugs can be loaded, thus synergism and multi-factorial effects are feasible.

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).

Anticoagulant and antimicrobial finishing of non-woven polypropylene textiles.

The aim of this work is to prepare non-woven polypropylene (PP) textile functionalized with bioactive molecules in order to improve its anticoagulation and antibacterial properties. This paper describes the optimization of the grafting process of acrylic acid (AA) on low-pressure cold-plasma pre-activated PP, the characterization of the modified substrates and the effect of these modifications on the in vitro biological response towards cells. Then, the immobilization of gentamicin (aminoglycoside antibiotic) and heparin (anticoagulation agent) has been carried out on the grafted samples by either ionic interactions or covalent linkages. Their bioactivity has been investigated and related to the nature of their interactions with the substrate. For gentamicin-immobilized AA-grafted samples, an inhibition radius and a reduction of 99% of the adhesion of Escherichia coli have been observed when gentamicin was linked by ionic interactions, allowing the release of the antibiotic. By contrast, for heparin-immobilized AA-grafted PP samples, a strong increase of the anticoagulant effect up to 35 min has been highlighted when heparin was covalently bonded on the substrate, by contact with the blood drop.

Safety, healing, and efficacy of vascular prostheses coated with hydroxypropyl-ß-cyclodextrin polymer: experimental in vitro and animal studies.

OBJECTIVES: Polyester vascular prostheses (PVPs) coated with a polymer of hydroxypropyl-ß-cyclodextrin (HPßCD) have been designed to provide an in situ reservoir for the sustained delivery of one or more bioactive molecules. The goal of this study was to assess the efficacy, the safety and the healing properties of these prostheses. METHODS: Collagen-sealed PVPs were coated with the HPßCD-based-polymer (PVP-CD) using the pad-dry-cure textile finishing method and loaded with one or two antibiotics. Appropriate control and PVP-CD samples were tested in several in vitro and animal model conditions. The study end points included haemolysis, platelet aggregation, antibacterial efficacy, polymer biodegradation, acute toxicity and chronic tolerance. RESULTS: PVP-CD proved to be compatible with human blood, since it did not induce haemolysis nor influenced ADP-mediated platelet aggregation. Sustained antimicrobial efficacy was achieved up to 7 days against susceptible bacteria when PVP-CDs were loaded with the appropriate drugs. Analysis of harvested PVP-CD from the animal model revealed that the HPßCD-based coating was still present at 1 month but had completely disappeared 6 months after implantation. All grafts were patent, well encapsulated without healing abnormalities. Clinical data, blood-sample analysis and histological examination did not evidence any signs of acute or chronic, local or systemic toxicity in the animal models. CONCLUSION: PVP-CD was proved safe and demonstrated excellent biocompatibility, healing and degradation properties. Effective antimicrobial activity was achieved with PVP-CD in conditions consistent with a sustained-release mechanism.

Secular trends of hip fractures in Québec, Canada.

UNLABELLED: This study examined the secular trends of hip fracture incidence among individuals 50 years and older in Québec between 1993 and 2004. Age-standardized rates decreased at both the provincial and regional levels. The largest relative decrease was observed among younger females, and rates declined more slowly in the elderly. INTRODUCTION: The population of the province of Québec is among the oldest in North America. Before the trend rupture reported in the late 1990s in several countries, hip fracture (HF) incidence rates did not show a secular trend (between 1981 and 1992). This study examined the secular trends of HF incidence at the provincial level and in two of the most important urban areas of the province, Montréal and Québec City, between 1993 and 2004. METHODS: All hospitalisations of individuals 50 years and older living in the province of Québec between 1993 and 2004 with a main diagnosis of HF were included. Standardized rates of HF incidence were calculated for females and males, 50-74 years and 75 years and older. RESULTS: The Québec City area showed a strong decreasing trend in HF rates for younger females, but the other groups did not show an obvious trend. Although our models did not support the existence of significant differences in trends between both areas, the rates of HF of younger males and, to a lesser extent, of older women in the Montréal area were significantly higher than in the Québec City area. CONCLUSIONS: Differences observed in hip fracture rates as well as in secular trends between age groups and gender emphasise the need for decision makers to rely on results based on age-specific and sex-specific analyses.

Selective biological response of human pulmonary microvascular endothelial cells and human pulmonary artery smooth muscle cells on cold-plasma-modified polyester vascular prostheses.

The aim of this work was to improve the hemocompatibility and the selectivity according to cells of non-woven poly(ethylene terephthalate) (PET) membranes. Non-woven PET membranes were modified by a combined plasma-chemical process. The surface of these materials was pre-activated by cold-plasma treatment and poly(acrylic acid) (PAA) was grafted by the in situ free radical polymerization of acrylic acid (AA). The extent of this reaction and the number of carboxylic groups incorporated were evaluated by colorimetric titration using toluidine blue O. All samples were characterized by SEM, AFM and thermogravimetric analysis, and the mechanical properties of the PAA grafted sample were determined. A selective cell response was observed when human pulmonary artery smooth muscle cells (HPASMC) or human pulmonary micro vascular endothelial cells (HPMEC) were seeded on the modified surfaces. HPASMC proliferation decreased about 60%, while HPMEC proliferation was just reduced about 10%. PAA grafted samples did not present hemolytic activity and the platelet adhesion decreased about 28% on PAA grafted surfaces.

Cyclodextrin and maltodextrin finishing of a polypropylene abdominal wall implant for the prolonged delivery of ciprofloxacin.

The aim of this work was to develop a polypropylene (PP) artificial abdominal wall implant for the prolonged release of ciprofloxacin (CFX). This sustained release effect was obtained by functionalization of the textile mesh with citric acid and hydroxypropyl-γ-cyclodextrin (HPγCD) or maltodextrin (MD). In both cases the textile finishing reaction yielded a cyclo- or malto-dextrin crosslinked polymer coating the fibers. The modified supports were characterized by thermogravimetric analysis (TGA), differential scanning calorimetry and scanning electron microscopy. The sorption capacities and the kinetics of CFX release were studied by batch tests coupled with spectrophotometric assays. Microbiological assays were carried out on Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli, while proliferation and viability tests used fibroblasts. The main results were as follows. (i) Due to the differences between the range of temperature of thermal degradation of the (cyclo)dextrins polymers and of the PP fibers TGA was a reliable method for quantifying the degree of functionalization of the textiles. (ii) Both modified supports showed improved sorption/desorption capacities for CFX, compared with the virgin mesh. The HPγCD-finished support showed an increased sorption capacity and a lower release rate of CFX compared with the MD modified support. (iii) Microbiological assays confirmed the latter result, with greater sustained antibacterial activity of the HPγCD treated support. These experiments have demonstrated the role of the cyclodextrin cavity in interactions with CFX: the antibiotic was not only adsorbed via hydrogen and acid-base interactions with the polyCTR-HPγCD network, but also via host-guest complexation. (iv) Biological tests revealed a slight decrease in fibroblast proliferation after 6 days on the modified supports, but cell viability tests showed that this was not due to toxicity of the (cyclo)dextrin polymer coatings.