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Facial angiofibromas are one one of the key features of tuberous sclerosis complex (TSC). They impair quality of life by disfiguring the patients who find them being affected in their body image. Several types of treatment have been tested over time; yet they were all disappointing in the long term. We tried to verify whether topical rapamycin is an efficient and safe therapeutic option in the management of facial angiofibromas. We used sirolimus (Rapamune) 0, 1% in petrolatum, twice a day. It is a retrospective, non-double-blind, non-randomized study, conducted in our Dermatology department at Saint-Luc University Hospital in Brussels from April 2013 to August 2015. The follow-up duration varied between 1 to 27 months depending on the patient (average of 14, 5 months). The safety evaluation was possible through a complete blood count ant dosage of sirolimus every 1-2-6 months then every 3 to 6 months. In order to assess the efficacy of our treatment, we based our conclusions on the comparison between before and after treatment pictures and on an estimated percentage expressed by the patient himself on his clinical improvement. All our patients, except for one who has interrupted the treatment, showed a clinical enhancement of their lesions: angiofibromas appear to have shrunk and they are less inflamed. Side effects are essentially limited to an irritative dermatitis. Rapamycin was never detected in the blood of these patients. Our results globally reflect what other case reports and studies say in medical literature. Topical rapamycin seems to be a safe and efficient strategy to manage facial angiofibromas for a period over 2 years. However, we need more comparative studies to definitively establish the ideal dose of sirolimus and the ultimate duration of the treatment. Les angiofibromes du visage sont une des atteintes cutanées les plus emblématiques de la sclérose tubéreuse de Bourneville. Ils portent un préjudice esthétique considérable à l’image corporelle de ces patients, menaçant ainsi leur qualité de vie : un grand nombre de stratégies thérapeutiques ont été mise en œuvre dans le temps ; elles se sont démontrées insatisfaisantes sur le long terme. Vérifier si le sirolimus topique constitue une option thérapeutique efficace et sure dans le traitement des angiofibromes du visage. 13 patients (dont 9 de sexe féminin et 6 mineurs) avec un diagnostic clinique de sclérose tubéreuse de Bourneville, ont donné leur accord pour essayer une crème à base de rapamycine sur leurs lésions angiofibromateuses du visage. Il s’agit de sirolimus (Rapamune) 0,1 % dans du pétrolatum appliqué 2 fois par jour. C’est une étude rétrospective, non double aveugle et non randomisée, menée dans le service de dermatologie des Cliniques Universitaires Saint-Luc, à Bruxelles du mois d’avril 2013 au mois d’août 2015. Le temps de suivi varie entre 1 et 27 mois selon le patient (moyenne de 14,5 mois). L’évaluation de la sécurité est effectuée via un hémogramme et un dosage sanguin de sirolimus à 1-2-6mois puis tous les 3 à 6 mois. On a évalué l’efficacité du traitement en comparant les photos avant et après traitement et selon un pourcentage arbitraire que le patient exprime à propos de son degré d’amélioration clinique. Tous les patients, sauf un qui a arrêté le traitement, montrent une amélioration clinique de leurs lésions : les angiofibromes sont réduits en volume et inflammation. Les effets indésirables se résument essentiellement à une dermatite irritative aux endroits d’application (8 patients sur 13). Le sirolimus n’est jamais détecté dans le sang chez les patients bénéficiant de contrôles biologiques réguliers. Nos résultats sont globalement en accord avec d’autres case reports et études à ce sujet. La rapamycine topique semble être une option sûre et efficace dans le traitement d’angiofibromes du visage pendant une durée qui dépasse les 2 ans. Plus d’études comparatives sont nécessaires pour établir de manière définitive la concentration idéale en principe actif, la meilleure forme galénique et la durée de traitement qui permettraient un effet bénéfique prolongé dans le temps.

Sirolimus --- Angiofibroma --- Tuberous Sclerosis

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Cancer --- Rapamycin. --- Molecular aspects. --- Sirolimus --- Immunosuppressive agents --- Macrolide antibiotics

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Development of new drug molecules is costly and requires longitudinal, wide-ranging studies; therefore, designing advanced pharmaceutical formulations for existing and well-known drugs seems to be an attractive device for the pharmaceutical industry. Properly formulated drug delivery systems can improve pharmacological activity, efficacy and safety of the active substances. Advanced materials applied as pharmaceutical excipients in designing drug delivery systems can help solve problems concerning the required drug release—with the defined dissolution rate and at the determined site. Novel drug carriers enable more effective drug delivery, with improved safety and with fewer side effects. Investigations concerning advanced materials represent a rapidly growing research field in material/polymer science, chemical engineering and pharmaceutical technology. Exploring novel materials or modifying and combining existing ones is now a crucial trend in pharmaceutical technology. Eleven articles included in the the Special Issue “Advanced Materials in Drug Release and Drug Delivery Systems” present the most recent insights into the utilization of different materials with promising potential in drug delivery and into different formulation approaches that can be used in the design of pharmaceutical formulations.

Technology: general issues --- mesoporous silica --- layer-by-layer --- FITC-peptide --- hyaluronic acid --- multilayer film --- host-guest interaction --- total alkaloids from Alstonia scholaris leaves --- mPEG-PLA --- microspheres --- drug release --- biocompatibility --- CO administration --- therapeutic agent --- pharmaceutical drugs --- heme oxygenase --- CO-releasing materials --- CO-releasing molecules --- organometallic complexes --- pharmacokinetic functions --- pathological role --- CO kinetic profile --- cellular targets --- GQDs --- real-time tracking --- optical-magneto nanoparticles --- in vivo --- ethylcellulose --- polymeric material --- cellulose derivative --- pharmaceutical excipient --- hydrogel --- drug delivery --- polymer --- immobilization of drug --- gelatin --- gastro-resistant --- films --- capsules --- structure --- sirolimus --- electrospinning --- polycaprolactone --- 3D matrix --- drug-eluting stents --- spray drying --- microparticles --- rupatadine fumarate --- orodispersible minitablets --- taste masking --- Bicalutamide --- Poloxamer® 407 --- Macrogol 6000 --- supercritical carbon dioxide --- solid dispersions --- dissolution rate --- amorphization --- 3D printing --- fused deposition modeling --- hot-melt extrusion --- solid dosage forms --- itraconazole --- n/a

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Development of new drug molecules is costly and requires longitudinal, wide-ranging studies; therefore, designing advanced pharmaceutical formulations for existing and well-known drugs seems to be an attractive device for the pharmaceutical industry. Properly formulated drug delivery systems can improve pharmacological activity, efficacy and safety of the active substances. Advanced materials applied as pharmaceutical excipients in designing drug delivery systems can help solve problems concerning the required drug release—with the defined dissolution rate and at the determined site. Novel drug carriers enable more effective drug delivery, with improved safety and with fewer side effects. Investigations concerning advanced materials represent a rapidly growing research field in material/polymer science, chemical engineering and pharmaceutical technology. Exploring novel materials or modifying and combining existing ones is now a crucial trend in pharmaceutical technology. Eleven articles included in the the Special Issue “Advanced Materials in Drug Release and Drug Delivery Systems” present the most recent insights into the utilization of different materials with promising potential in drug delivery and into different formulation approaches that can be used in the design of pharmaceutical formulations.

Technology: general issues --- mesoporous silica --- layer-by-layer --- FITC-peptide --- hyaluronic acid --- multilayer film --- host-guest interaction --- total alkaloids from Alstonia scholaris leaves --- mPEG-PLA --- microspheres --- drug release --- biocompatibility --- CO administration --- therapeutic agent --- pharmaceutical drugs --- heme oxygenase --- CO-releasing materials --- CO-releasing molecules --- organometallic complexes --- pharmacokinetic functions --- pathological role --- CO kinetic profile --- cellular targets --- GQDs --- real-time tracking --- optical-magneto nanoparticles --- in vivo --- ethylcellulose --- polymeric material --- cellulose derivative --- pharmaceutical excipient --- hydrogel --- drug delivery --- polymer --- immobilization of drug --- gelatin --- gastro-resistant --- films --- capsules --- structure --- sirolimus --- electrospinning --- polycaprolactone --- 3D matrix --- drug-eluting stents --- spray drying --- microparticles --- rupatadine fumarate --- orodispersible minitablets --- taste masking --- Bicalutamide --- Poloxamer® 407 --- Macrogol 6000 --- supercritical carbon dioxide --- solid dispersions --- dissolution rate --- amorphization --- 3D printing --- fused deposition modeling --- hot-melt extrusion --- solid dosage forms --- itraconazole --- n/a

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Absorbable metals have shown significant clinical potential for temporary implant applications, where the material is eventually replaced by healthy, functioning tissue. However, several challenges remain before these metals can be used in humans. Innovations and further improvements are required. This book collects scientific contributions dealing with the development of absorbable metals with improved and unique corrosion and mechanical properties for applications in highly loaded implants or cardiovascular and urethral stents.

surface treatments --- roughness --- Mg-alloys --- degradation behavior --- absorbable --- corrosion --- degradation --- magnesium --- ureteral stent --- zinc --- mandibular condylar fracture --- unsintered hydroxyapatite/poly-l-lactide composite plate --- bioactive resorbable plate --- biomechanical loading evaluation --- fracture fixation --- WE43/HA composite --- friction stir processing --- microstructure --- mechanical properties --- corrosion behavior --- absorbable metal --- cytotoxicity --- stent --- ureteral --- urothelial cells --- zinc alloy --- poly-L-lactide --- uncalcined and unsintered hydroxyapatite --- biocompatibility --- osteoconductivity --- mesenchymal stem cell --- iron foam --- polyethyleneimine (PEI) --- biodegradation --- powder metallurgy --- coating --- biodegradable magnesium implants --- bioceramics --- bioactivity --- orthopedic implant --- bone surgery --- absorbable implants --- magnesium (Mg) --- oral and maxillofacial --- orthopedic --- titanium (Ti) --- biomaterials --- electrochemistry --- hydrogen evolution --- microscopy --- Mg-Zn-Sn alloy --- osteoinductive activity --- sirolimus --- rabbit coronary artery endothelial cells --- smooth muscle cells --- bioabsorbable metals --- in-vivo biocompatibility --- strontium --- toxicity --- systemic reactions --- alloy accumulation --- internal organs --- iron --- corrosion rate --- biodegradable material --- n/a