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Biomedical subjects

C Damge

Publications and source records attributed to C Damge.

11 recordsLinked to original sources

Formulation of insulin-loaded polymeric nanoparticles using response surface methodology.

The objective of this work was to formulate new oral insulin-loaded nanoparticules using the response surface methodology. The insulin nanoparticles were prepared by a water-in-oil-in-water emulsification and evaporation method. The polymers used for the encapsulation were blends of biodegradable poly-epsilon-caprolactone (PCL) and of positively-charged, nonbiodegradable polymer (Eudragis RS). A central composite design has been built to investigate the effects of three controlled variables: ratio of polymers (PCL/RS ratio), volume, and pH of the aqueous solution of polyvinyl alcohol. The nanoparticles were characterized by measuring the amount of entrapped insulin, the particle size, the polydispersity of the obtained particles, the zeta potential, and the amount of insulin released after 7 hours. A second-order model was evaluated by multiple regression and was statistically tested for each of the studied controlled variable. The obtained polynomials proved efficient to localize an optimal operating area highlighted by the use of three-dimensional response surfaces and their corresponding isoresponse curves. An interesting formulation given by the models was selected, prepared, and evaluated. The corresponding quantity of entrapped insulin was 25 IU per 100 mg of polymer, and the particle size was 350 nm with a polydispersity of 0.21. The quantity of released insulin was 4.8 IU per 100 mg of polymer after 7 hours and the zeta potential was +44 mV. All these collected values were in perfect accordance with values estimated by the models. Finally, the results suggested that PCL/RS 50/50 nanoparticles might represent a promising formulation for oral delivery of insulin.

Administration, Oral↗

Biomaterial supports for colonic wall defect healing. An experimental study in the rat.

New artificial biomaterials were tested for support of gastro-intestinal tract wound healing in the rat. Double layered collagenic matrices were prepared with purified collagens extracted from human placental tissues. Two types of patches were tested, the first constituted from a collagen type I + III layer covered by collagen IV in a liquid phase (patch I + III/IV) and the second from a collagen IV layer covered by liquid collagen IV (patch IV/IV). The matrices were applied with fibrin sealant to the edges of a 1 cm diameter colonic wall defect in the rat. Healing evolution was determined by macroscopic, microscopic and immunostaining studies. The reconstitution of the three colonic wall layers was achieved within 45 days without retraction or inflammatory reaction, while the biomaterial was resorbed. Human collagen I and III antibodies failed to stain extracellular matrix. This failure may be a consequence of outdated antibodies or more likely epitope alteration during extraction and preparation of the collagens. A human collagen type IV antibody staining of the scar zone showed the basement membranes of newly developed vessels within 10 days, and newly formed colonic mucosa within 20 days. The collagen reconstituted matrix was able to assist healing of normal digestive tract defects as shown by the labelling of the new synthesized extracellular matrix by collagen type IV antibody. These findings support the use of collagen biomaterial in gastro-intestinal anastomosis. This new surgical approach allowing healing of colonic wall defects could reduce occurrence of anastomotic leakage in human.

Animals↗

[Photodynamic therapy in oncological digestive tract surgery].

Photodynamic therapy is a useful new antitumoral treatment, since it is relatively selective and noniatrogenic. The photosensitizers become preferentially localized in the tumoral tissue, where their excitation by light causes the production of free cytotoxic radicals. If haematoporphyrin derivatives are the most widely used photosensitizers, numerous molecules are being tested. Now used as a palliative photodynamic therapy could logically be used as adjuvant treatment in curative surgical excision. The practical utility of peroperative photodynamic therapy in gastroenterological surgery is being evaluated experimentally and clinically.

Chlorophyll↗

Prevention of anastomosis leakage: an artificial connective tissue.

Anastomosis leakage still causes considerable morbidity and mortality after digestive tract surgery. We report here our experience of the use of reconstituted connective tissue created from elastin, fibronectin and collagen in preventing anastomosis leakage and closing intestinal fistulas. In animal studies (56 rats), this connective tissue was used as a patch applied with fibrin sealant to the edges of a 1 cm diameter colonic defect. In a clinical evaluation, eight patients had an intestinal fistula closed by a simple sewn suture reinforced by a sealed patch and seven patients had a high risk anastomosis reinforced by a sealed patch, in most cases as an alternative to staged surgery. In animal studies, complete reconstitution of the three colonic layers was obtained without retraction and without inflammatory reaction within 40 days, while the patch was slowly resorbed. In clinical trials all 15 defects and anastomoses healed without complication. Three patients died from other causes and, at autopsy, the patch was found to have remained in place covering the suture line. If these results are confirmed by a prospective clinical trial, such biomaterial offers the possibility of reducing the occurrence of anastomosis leakage, especially in high risk circumstances.

Adult↗

A new reconstituted connective tissue matrix: preparation, biochemical, structural and mechanical studies.

A fibrinogen derivative generated by thrombin was reacted with elastin to yield a new addition product or adduct between the two proteins. Addition of fibronectin, and then of collagen, did not interfere with the basic elastin-fibrinogen reaction and conferred the qualities of an artificial connective tissue to the product. Biochemical, structural and biomechanical aspects of the new matrix were studied. Aprotinin, heparin, thiomersal, and thiourea did not inhibit the main reaction; indeed, some of these ingredients improved the matrix cohesion. Scanning electron microscopy showed the genesis of a true network whose meshes were more reticulated by the addition of thiourea. Biomechanical studies, i.e., strength and elasticity showed the thiourea matrix to be the strongest. These intrinsic properties suggest the product could have biological and clinical applications.

Biocompatible Materials↗

Transmucosal passage of polyalkylcyanoacrylate nanocapsules as a new drug carrier in the small intestine.

The enteral absorption of particles has been investigated in the dog using a colloidal drug carrier, polyalkylcyanoacrylate nanocapsules loaded with an iodized oil (Lipiodol), as a tracer for X-ray microprobe analysis in a scanning electron microscope. Nanocapsules are spherical capsules, 100 to 200 nm in diameter, with a continuous polymeric wall surrounding a cavity which encapsulates the drug. Administered in the jejunal lumen, Lipiodol nanocapsules improved the absorption of the tracer as indicated by increased concentration of iodine in the plasma of mesenteric blood. In order to follow nanocapsules at the cellular level, all tissue compartments were preserved in a life-like state by cryofixation and freeze-drying of intestinal biopsies. Nanocapsules appeared in the intestinal lumen close to the mucus, then in intercellular spaces and defects of the mucosa and finally in the lamina propria and blood capillaries; in this latter compartment, the iodine content was four-fold higher than after intra-jejunal administration of Lipiodol emulsion. This complete phenomenon occurred only at the tip of the villi and happened within less than 60 min. We conclude that nanocapsules enhance the rate of absorption of Lipiodol and transport the drug from the intestinal lumen to the vascular compartment using a paracellular pathway. Thus they may be useful as drug carrier for oral administration of many chemicals.

Animals↗

[Vascular malformations of the colon. A frequently undetected etiology of lower digestive hemorrhage].

Angiectasia of the right colon is a new entity which must be considered in cases of lower intestinal haemorrhage. Moore's classification is the one that is generally accepted today; it distinguishes between 3 types the most interesting and best individualized of which is type I. It consists of acquired lesions occurring after the age of 60, often multiple, localized in the right colon and frequently associated with aortic stenosis and atheroma. The diagnosis of these vascular malformations is usually delayed because the lesions are submucosal and not visible at endoscopy. Bimesaraic arteriography may show typical images where extravasation of contrast medium is associated with vascular tuft or "tuff". Even the anatomicopathological confirmation of the diagnosis is difficult, since the lesion can only be located by special techniques, such as intra-arterial injection of a silicone-containing substance. Owing to the failure of modern techniques such as embolization, the only possible treatment is surgical, based on resection of the colonic segment involved.

Arteriovenous Malformations↗

[Mechanical sutures in digestive surgery. A critical study].

An objective review of the experimental and clinical literature comparing stapled- and hand-sutured anastomoses in gastrointestinal surgery is presented. Experimental studies support the hypothesis that stapled-sutured lines heal by primary intention, thus avoiding the inflammatory time lag, and resulting in a stronger wound during the first post-operative week. In contrast, manual sutures always produce an early inflammatory reaction with a transitory rise in collagenase activity in the submucosa, which explains the particular fragility of the anastomosis during that phase. Nevertheless, it was difficult to find a concordance between this histological quality of the stapled suture line and clinical results. In oesophageal surgery, a slightly higher rate of stenosis and a lower rate of anastomotic leakage were observed. In gastric and colorectal surgery, the superiority of the stapled suture was not proved. However, in colorectal randomized studies, the presence of "withdrawn" group for which the stapler was the only technically possible alternative, provides undeniable proof that this technique is an indispensable adjunct in modern digestive surgery. Conversely, its value seems negligible in surgery of the small bowel or of the intraperitoneal colon where manual suturing remains the technique of choice.

Acute-Phase Reaction↗