Una concreta possibilità per il futuro

Il progetto più vicino nell’essere realizzato è quello di riuscire a costruire degli impianti, dei sensori della glicemia, miniaturizzati con i quali non sia più necessario auto-calibrare i sensori, o comunque dispositivi in grado di essere indossati per un arco temporale maggiore. Sempre tra i progetti oramai in porto c’è quello di migliorare la via di somministrazione dell’insulina favorendone anche l’assorbimento in situ così da eliminare la necessità di una somministrazione prima dei pasti. I dispositivi progettati sono infatti capaci di utilizzare un algoritmo di controllo che determina l’adattamento del rilascio insulinico in base all’individualità del paziente così da evitare i classici e frequenti errori di calcolo legati o alla conta dei carboidrati da parte del paziente o all’inappropriato segnale recepito dal sensore del glucosio.

La terapia che viene proposta risulta quindi essere estremamente personalizzata e pare poter essere applicata anche a coloro che soffrono di diabete mellito di tipo 2 ma e necessitano di assumere insulina. Inoltre, non trattandosi di un organo, questo approccio evita le difficoltà che si possono incontrare nel trapiantare le cellule pancreatiche, come risposte immunitarie difficilmente controllabili.

BIBLIOGRAFIA

1) www.istat.it/il-diabete-in-Italia

2) Global Report on Diabetes. World Health Organization, 2014.

3) Il Diabete Mellito, Felice Citriniti, Daniela Musca. Ospedale “Pugliese” di Catanzaro. SOC Pediatria. XVII Congresso della SIEDP, Napoli, Novembre 2009 4) www.diabete.net/diabete-tipo-2-caratterisctiche-cause-e-sintomi/vivere-con-il-

diabete/il-diabete-di-tipo-2/31202/

5) www.museodeldiabete.com/storia14htm

6) http://www.diabetescore.it/news/179-l-insulina-degludec-durata-ancora-piu- lunga.html

7) Presente e futuro della terapia insulinica nel bambino e adolescente con diabete mellito di tipo 1. S. Tumini, F. Lombardo, G. d’Annunzio. G It Diabetol Metab 2014;34:124-132.

8) Opinioni a confronto. A cura di Stefano Del Prato Dipartimento di Endocrinologia e Metabolismo, Sezione Diabetologia e Malattie del Metabolismo, Università di Pisa. Insulina inalata. Partecipanti Giovanni Anfossi, Mariella Trovati (Dipartimento di Scienze Cliniche e Biologiche dell’Università di Torino) Brunella Capaldo (Dipartimento di Medicina Clinica e Sperimentale, Università Federico II, Napoli). Il Diabete. Vol 19 n°3. Settembre 2007.

9) http://www.diabete.net/l-4/tuttodiabete/archivio/anno-23-n2-aprile-giugno- 2006/23717/

10) http://www.AIFA.gov.it/EXUBERA Allegato 1. Caratteristiche del prodotto. 11) Comparative lung cancer mortality with inhaled insuline or comparator: FUSE

final results, Gatto NM, Koralek DO, Brake MB, Dugnano WT, Leni J, Kliaze SS, Jackson NC. ICPE, August 24, 2012

12) http://www.healthline.com/diabetesmine/story-inhaled-insulin-so-far#5 The story of Inhaled Insulin, written by Amy Tenderich, published on 1 giugno 2016

13) http://www.xagenasearch.it Rosenstock J et al, Diabetes Care 2004; 27: 1318- 1323

14) Afrezza (insulin human) inalazione Power PT 2015 Nov; 40 (11):735-741. Tamara Goldberg, Elaine Wong

15) Pharmacokinetic characterization of Novel pulmonary delivery excipient fumaryl diketopiperazine. Elizabeth Potacka, James Cassidy, Pamela Haworth, Douglas Heumann, Pharm.D, Ph.D. Journey of diabete Science and Technology 2010 Sept

16) Techosphere Insulin: defining the role of technosphere particles at the cellular level J DIABETES SCI TECHNOL. 2009 May, 3(3):545-554

17) Shows AFREZZA(R) Controls Blood Sugar Levels in Type 1 Diabetes, Results in Weight Loss, Less Hypoglycemia Than Usual Care. Boston, Apr 23, 2010 18) MannKind reports positive results from final two pilotal phase 3 clinical studies in

type 1 and type 2 diabetes. Matthew J. Pfeffer, Corporate Vice President and Chief Financial Officer of MannKind Corporation. December 2008. http://www.mannkindcorp.com/

19) AFREZZA® (insulin human) Inhalation Powder. http://www.mannkindcorp.com/our-technology-patent-notices.htmMannKind Corporation, Danbury, CT 06810 Revised: 04/2016

20) Department of Health and Human Services Public Health Service Food and Drug Administration Center for Drug Evaluation and Research Office of Surveillance and Epidemiology (OSE) Office of Pharmacovigilance and Epidemiology (OPE). Epidemiology Summary: Review of Study Protocol. Patricia L. Bright, M.S.P.H., Ph.D., Diane K. Wysowski, M.P.H. February 28, 2014

21) The thruth about Afrezza inhaled insulin: a chat with Al Mann. Amy Tenderich, 17 November 2009

22) http://www.cbsnews.com/news/mannkind-has-mountain-to-climb-if-fda-

approves-afresa-and-technosphere/ MannKind has Mountain to climb if FDA approves Afresa and Technosphere Jul, 9 2009 3:41 PM EDT

23) http://dancebiopharm.com/Dance-501/

24) Jet, Ultrasonic, and Mesh Nebulizers: An Evaluation of Nebulizers for Better Clinical Outcomes, Arzu Ari, 2014, Eurasian Journal of Pulmonology 2014; 16: 1-7.

25) Adagio Phase I/II data. Dance Biopharm Inc., August 19, 2013. http://www.biocentury.com/weekinreview/clinicalresults/2013-08-19/adagio- phase-iii-data-327500

26) Oral insuline capsules: Clinical highlights. Miriam Kidron PhD, Roy Eldor M.D and Ehud Arbit M.D. oramed Pharmaceuticals, Jerusalem, Israel. Yale Poster, may, 2014-

27) Https://www.diabetesincontrol.com/ November, 22 2016

28) Generex OrallynTM Delivered by RapidMistTM Spray System Evolution of a Concept to a Viable Pharmaceutical Product. Generex Oral-lyn White paper August, 2015

29) University of Toronto’s Center for Molecular Design and Pre‐

formulations (CMDP). Dr. Lakshmi P. Kotra. http://www.generex.com/

30) OrallynFactSheet.pdf Oral Insuline Spray Treatment for type 1 & type 2 Diabetes. Generex Biotechnology Corporation. Veterinary College of the University of Guelph, Ontario. 2016

31) http://www.gea.com/it/applications/phamax-solid-dosage/solid-dosage- contonuostobleting.jsp

32) Https://www.notiziariofarmaceutico.it/2016/04/04/produzone-on-demond

33) Glucose-Reducing Effect of the ORMD-0801 Oral Insulin Preparation in Patients with Uncontrolled Type 1 Diabetes: A Pilot Study. Roy Eldor, Ehud Arbit, Asher Corcos, Miriam Kidron, Franco Folli. University of Texas Health Science Center at San Antonio, United States of America. April 9, 2013

34) Pharmacokinetic and pharmacodynamic Profile of orally doudenally and subcutaneusly delivered insulin in Beagle Canines. ADA-POSTER-2016.

35) Comparative assessment of the glucose-lowering effect of multiple oral insulin (ORMD-0801) formulation variants in pigs. Miriam Kidron, Ehud Arbit, Yael Shushlav. Abstracts, 74th Scientific Sessions of the American Diabetes Association. June 13-17,2014

36) Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery. Jicheng Yu, Yuqi Zhang, Yanqi Ye, Rocco

DiSanto, Wujin Sun, Davis Ransona, Frances S. Ligler, John B. Busec, and Zhen Gu. Edited by Dean Ho, University of California, Los Angeles, CA, May 19, 2015 PNAS.

37) Microneedles Integrated with Pancreatic Cells and Synthetic Glucose-Signal Amplifi ers for Smart Insulin Delivery. Yanqi Ye, Jicheng Yu, Chao Wang, Nhu-Y Nguyen, Glenn M.Walker, John B.Buse, and Zhen Gu. Advanced Materials 2016, 28, 3115-3121.

38) Formulation of two-layer dissolving polymeric microneedle patches for insulin transdermal delivery in diabetic mice. I-Chi Lee, Wei-Ming Lin,Jwu-Ching Shu, Shau-Wei Tsai, Chih-Hao Chen, Meng-Tsan Tsai. Journal of Biomedical Materials Reserch, August 2016. DOI:10.1002/jbm.a.35869

39) Secretion of the incretin hormones glucagon-like peptide-1 and gastic inibitory polypeptide correlates with insulin secretion in normal man throughout the day. Orskov, Wettergren, Holst. Scad J Gastroenterol 1996; 31: 665-670

40) Continuous subcutaneus unsulin infusion (CSII) in Italy. BRUTTOMESSO, COSTA, CRAZZO, DI BARTOLO, GIRELLI. Diabetes Res Clin Pract 2002 41) Terapia Insulinica con microinfusore in giovani pazienti affetti da DMT1. Allais B;

Albanesi M; Scaglia F; Caremagna C; Merli P; Calcaterra V. Clinica Pediatrica Universitaria di Pavia, 2009.

42) OpT2mise: A randomized controlled trial to compare insulin pump therapy with multiple daily injections in the treatment of type 2 diabetes. Diabetes Technol There, 2014. Aranson R, Cohen O, Conget I et al.

43) Closed-loop insulin delivery for treatment of type1 diabetes, Ellerin et al. BMC Medicine 2011, 9:120

44) Philip M, Battelino T. Atlas E et al (2013) Nocturnal glucose control with an artificial pancreas at diabetes Camp. N Enge J Med 368:824-833

45) Coming of age: the artificial pancreas for type 1 diabetes. Thabit & Havorka. 30 June 2016. R.Diabetologia

46) https://diatribe.org/drugdevice-name/medtronic-minimed-670g 2016:A pivotal year for closed loop/automated insulin delivery. Adam Brown and Brian Levine, Dec 10, 2016

47) Artificial pancreas device system for the closed-loop control type 1 diabetes: what system are development? Trevitt S, Simpson S, Wood A (2015) J Diabetes Sci Technol 10:714-723