Öz
Dünya üzerinde en fazla üyeye sahip kronik hastalıklardan biri olan diyabet için, özellikle tip 1 diyabetli hastalarda, vücutta üretilen insülinin görevlerini tam olarak karşılayabilen tedavi yöntemi henüz bulunamamıştır. Peptid yapılı bir makromolekül olan insülin, farklı uygulama yollarıyla verildiğinde enzimatik bozunmaya uğraması veya yeterince emilememesi sebebiyle çoğunlukla subkutan olarak uygulanır. Ancak rutin olarak subkutan ilaç uygulamak hastalarda birtakım immünolojik problemlere, yağ dokusu bozulduğundan lipodistrofi şikayetlerine sebep olabilmektedir. Ayrıca doğal olarak üretilen insülinle farmakokinetik özellikleri tam olarak uyuşmadığından hiperinsülinemi görülebilmektedir. Son yıllarda yapılan klinik çalışmalara göre hatırı sayılır oranda diyabet hastası insulinin enjeksiyonla yapılan tedavisine uyunç sağlayamadığından uzun vadede glisemik kontrol de sağlanamamaktadır. Oral dozaj şekilleri ile ilaç tedavisi uyunç ve uygulama kolaylığı sebebiyle en fazla tercih edilen sistemler olduğundan, subkutan insülin tedavisinin zorluklarına alternatif olarak oral insülin uygulanmasının yolu açılmaya çalışılmış ve formülasyonun uygulanması için öne çıkan problemlere çözüm aranmaya başlanmıştır. Nanoteknoloji, pek çok alanda olduğu gibi ilaç teknolojisinde de dikkat çekmeye başlamıştır. Nanofarmasötik sistemler geleneksel ilaçlara göre absorpsiyonu ve etkin madde için koruyuculuğu yüksek, terapötik seviyeye ulaşmak için gerekli doz miktarını azaltan, biyoyararlanımı artıran, kontrollü salım ve hedeflendirme yapabilme avantajlarını sağlayan, ilacın etki süresini azaltan sistemlerdir. Tüm bu avantajlar düşünüldüğünde, insülinin oral yoldan verilebilmesi için nanofarmasötiklerin uygunluğu in vitro ve in vivo deneylerle araştırılmaktadır.
Anahtar Kelimeler
Nano sistemler insülin oral uygulama diyabet biyoyararlanım oral peptidler
Kaynakça
- 1. Choonara BF, Choonara YT, Kumar P, Bijikumar D, Du Toit LC, Pillay V. A review of advanced oral drug delivery technologies facilitating the protection and absorption of protein and peptide molecules. Biotechnol Adv 2014; 32: 1269-82. [CrossRef] 2. Hwang SR, Byun Y. Advances in oral macromolecular drug delivery. Expert Opin Drug Deliv 2014; 11: 1955-67. [CrossRef] 3. Pamnani D. Reality Check on Oral Insulin. Pharma Express 2008. 4. Fonte P, Araújo F, Reis S, Sarmento B. Oral insulin delivery: how far are we? J Diabetes Sci Technol 2013; 7: 520-31. [CrossRef] 5. Collins, CE. A Short Course in Medical Terminology. 3rd Ed. USA: Lippincott Williams & Wilkins; 2013. p.160. 6. Akalın A, Akıncı B, Atabey A, Atmaca A, Atmaca H, Aydın H, ve ark. Diabetes Mellitus 2009: Multidisipliner Yaklaşımla Tanı, Tedavi ve İzlem. 2nd Ed. İmamoğlu Ş (ed). İstanbul, Turkey: Deomed; 2009. 7. Sheehan MT. Current therapeutic options in type 2 diabetes mellitus: A practical approach. Clin Med Res 2003; 1: 189-200. [CrossRef] 8. Brange J, Langkjær. Stability and Characterization of Protein and Peptide Drugs: Case Histories. Wang YJ, Pearlman R (eds). New York: Springer Science and Business Media; 1993. p. 315-50. [CrossRef] 9. Triplitt CL, Reasner CA, Isley WL. Diabetes mellitus. In: Pharmacotherapy, A Pathophysiologic Approach. 5th Ed. Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM (eds). New York: McGraw Hill; 2002. p. 1335-67. 10. Hall JE. Guyton and Hall Textbook of Medical Physiology. 12th Ed. Philedelphia: Saunders; 2011. p. 884-98. 11. Agarwal V, Khan MA. Current status of the oral delivery of insulin. Pharm Technol 2001; 25: 76-90. 12. Fischer A. The effect of molecular size on the nasal absorption of water soluble compounds in albino rat. J Pharm Pharmacol 1987; 39: 357-62. [CrossRef] 13. Acartürk F, Ağabeyoğlu İ, Araman A, Brannon-Peppas L, Çapan Y, Çelebi N, ve ark. Ed: Zırh-Gürsoy A. Kontrollü Salım Sistemleri. 2nd Ed. İstanbul: Kontrollü Salım Sistemleri Derneği; 2014. 14. Arbit E, Kidron M. Oral Insulin: The Rationale for This Approach and Current Developments. J Diabetes Sci Technol 2009; 3: 562-7. [CrossRef] 15. Chen MC, Sonaje K, Chen KJ, Sung HW. A review of the prospects for polymeric nanoparticle platforms in oral insulin delivery. Biomaterials 2011; 32: 9826-38. [CrossRef] 16. Bruno BJ, Miller GD, Lim CS. Basics and recent advances in peptide and protein drug delivery. Ther Deliv 2013; 4: 1443-67. [CrossRef] 17. Sonia TA, Sharma CP. Oral Delivery of Insulin. Woodhead Publishing; 2014. 18. Hamman JH, Enslin GM, Kotzé AF. Oral delivery of peptide drugs: Barriers and Developments. Biodrugs 2005; 19: 165-77. [CrossRef] 19. Kinesh VP, Neelam DP, Punit BP, Bhavesh SB, Pragna KS. Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products. Int J Pharm Sci Nanotech 2010; 3: 1057-64. 20. Brayden DJ, Mrsny RJ. Oral peptide delivery: prioritizing the leading technologies. Ther Deliv 2011; 2: 1567-73. [CrossRef] 21. Muheem A, Shakeel F, Jahangir MA, Anwar M, Mallick N, Jain GK, et al. A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives. Saudi Pharm J 2016; 24: 413-28. [CrossRef] 22. Acartürk F, Alpar HO, Arıca B, Bahadori F, Badıllı U, Başaran N, ve ark. Nanofarmasötikler ve Uygulamaları. Zırh-Gürsoy A (ed). İstanbul: Kontrollü Salım Sistemleri Derneği; 2014. 23. Cho HJ, Oh J, Choo MK, Ha JI, Park Y, Maeng HJ. Chondroitin sulfate-capped gold nanoparticles for the oral delivery of insulin. Int J Biol Macromol 2014; 63: 15-20. [CrossRef] 24. Sarmento B, Ribeiro A, Veiga F, Sampaio P, Neufeld R, Ferreira D. Alginate/ chitosan nanoparticles are effective for oral insulin delivery. Pharm Res 2007; 24: 2198-206. [CrossRef] 25. Goswami S, Bajpai J, Bajpai AK. Calcium alginate nanocarriers as possible vehicles for oral delivery of insulin. J Exp Nanosci 2014; 9: 337-56. [CrossRef] 26. Reis CP, Ribeiro AJ, Houng S, Veiga F, Neufeld RJ. Nanoparticulate delivery system for insulin: Design, characterization and in vitro/in vivo bioactivity. Eur J Pharm Sci 2007; 30: 392-7. [CrossRef] 27. Hosseininasab S, Pashaei-Asi R, Khandaghi AA, Nasrabadi HT, Nejati-Koshki K, Akbarzadeh A, et al. Synthesis, characterization and in vitro studies of PLGA-PEG nanoparticles for oral insulin delivery. Chem Biol Drug Des 2014; 84: 307-15. [CrossRef] 28. Zhang Y, Wu X, Meng L, Zhang Y, Ai R, Qi N, et al. Thiolated Eudragit nanoparticles for oral insulin delivery: Preparation, characterization and in vivo evaluation. Int J Pharm 2012; 436: 341-50. [CrossRef] 29. Sheng J, He H, Han L, Qin J, Chen S, Ru G, et al. Enhancing Insulin Oral Absorption by Using Mucoadhesive Nanoparticles Loaded with LMWP-linked Insulin Conjugates. J Control Release 2016; 233: 181-90. [CrossRef] 30. Chung H, Kim JS, Um J, Kwon I, Jeong S. Self- assembled ‘nanocubicle’ as a carrier for peroral insulin delivery. Diabetologia 2002; 45: 448-51. [CrossRef] 31. Sarmento B, Martins S, Ferreira D, Souto EB. Oral insulin delivery by means of solid lipid nanoparticles. Int J Nanomedicine 2007; 2: 743-9. 32. Zhang N, Ping Q, Huang G, Xu W, Cheng Y, Han X. Lectin-modified solid lipid nanoparticles as carriers for oral administration of insulin. Int J Pharm 2006; 327: 153-9. [CrossRef] 33. Niu M, Lu Y, Hovgaard L, Guan P, Tan Y, Lian R, et al. Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: The effect of cholate type, particle size and administered dose. Eur J Pharm Biopharm 2012; 81: 265-72. [CrossRef] 34. Zhang X, Qi J, Lu Y, He W, Li X, Wu W. Biotinylated liposomes as potential carriers for the oral delivery of insulin. Nanomedicine 2014; 10: 167-76. [CrossRef] 35. Cui M, Wu W, Hovgaard L, Lu Y, Chen D, Qi J. Liposomes containing cholesterol analogues of botanical origin as drug delivery systems to enhance the oral absorption of insulin. Int J Pharm 2015; 489: 277-84. [CrossRef] 36. Moghassemi S, Parnian E, Hakamivala A, Darzianiazizi M, Vardanjani MM, Kashanian S, et al. Uptake and transport of insulin across intestinal membrane model using trimethyl chitosan coated insulin niosomes. Mat Sci Eng C 2015; 46: 333-40. [CrossRef] 37. Hans ML, Lowman AM. Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 2002; 6: 319-27. [CrossRef] 38. Ma EL, Ma H, Liu Z, Zheng CX, Duan MX. In vitro and in vivo evaluation of a novel oral insulin formulation. Acta Pharmacol Sin 2006; 27: 1382-8. [CrossRef] 39. Rao SVR, Yajurvedi K, Shao J. Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of protein drugs: III: in vivo oral absorption study. Int J Pharm 2008; 362: 16-9. [CrossRef] 40. Zhang Q, He N, Zhang L, Zhu F, Chen Q, Qin Y, et al. The in vitro and in vivo study on self-nanoemulsifying drug delivery system (SNEDDS) based on insulin-phospholipid complex. J Biomed Nanotechnol 2012; 8: 90-7. [CrossRef] 41. Li P, Tan A, Prestidge CA, Nielsen HM, Müllertz A. Self-nanoemulsifying drug delivery systems for oral insulin delivery: In vitro and in vivo evaluations of enteric coating and drug loading. Int J Pharm 2014; 477: 390-8. [CrossRef] 42. Sakloetsakun D, Dünnhaupt S, Barthelmes J, Perera G, Bernkop-Schnürch A. Combining two technologies: Multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration. Int J Biol Macromol 2013; 61: 363-72. [CrossRef] 43. Kabanov AV, Vinogradov SV. Nanogels as Pharmaceutical Carriers: Finite Networks of Infinite Capabilities. Angew Chem Int Ed Engl 2009; 48: 5418-29. [CrossRef] 44. Morishita M, Goto T, Peppas NA, Joseph JI, Torjman MC, Munsick C, et al. Mucosal insulin delivery systems based on complexation polymer hydrogels: effect of particle size on insulin enteral absorption. J Control Release 2004; 97: 115-24. [CrossRef] 45. Foss AC, Goto T, Morshita M, Peppas NA. Development of acrylic-based copolymers for oral insulin delivery. Eur J Pharm Biopharm 2004; 57: 163-9. [CrossRef] 46. Ramkissoon-Ganorkar C, Liu F, Baudys M, Kim SW. Modulating insulin-release profile from pH/thermosensitive polymeric beads through polymer molecular weight. J Control Release 1999; 59: 287-98. [CrossRef] 47. Zhao D, Shi X, Liu T, Lu X, Qiu G, Shea KJ. Synthesis of surfactant-free hydroxypropyl methylcellulose nanogels for controlled release of insulin. Carbohyd Polym 2016; 151: 1006-11. [CrossRef] 48. Wang J, Xu M, Cheng X, Kong M, Liu Y, Feng C, et al. Positive/negative surface charge of chitosan based nanogels and its potential influence on oral insulin delivery. Carbohyd Polym 2016; 136: 867-74. [CrossRef] 49. Hoare T, Pelton R. Charge-switching, amphoteric glucose-responsive microgels with physiological swelling activity. Biomacromolecules 2008; 9: 733-40. [CrossRef] 50. Kroschewski R. Molecular mechanisms of epithelial polarity: about shapes, forces and orientation problems. Physiology 2004; 19: 61-6. [CrossRef]
Öz
Diabetes is among the major chronic diseases at present, and no medication has been developed that can replace the roles of endogenous insulin, especially for type 1 diabetes patients. However, insulin can be frequently administered by the subcutaneous route as a protein macromolecule because enzymatic and absorption-associated problems. It leads to immunogenic symptoms, adipose tissue complaints such as lipodystrophy, and hyperinsulinemia risks because of pharmacokinetic properties that do exactly overlap with those of endogenous insulin. In a remarkable number of patients, failure to attain permanent glycemic control by subcutaneous insulin treatment has shown by clinical trials based on noncompliance. Oral drug administration has always been the most preferred administration pathway for drugs with high patient compliance and convenience. Difficulties in the use of subcutaneous insulin have prompted scientists to find solutions for the oral administration of insulin. Similar to many other fields, nanotechnology has recently come to the fore in the pharmaceutical field. Compared with conventional systems, nanopharmaceuticals are drug delivery systems that enable promoted absorption, protection of the active ingredient from the external environment, lower dose applications, higher bioavailability, controlled release, and prolonged residence time. In vitro and in vivo studies have been performed with varied nanopharmaceutical systems in order to administer insulin orally for this purpose.
Anahtar Kelimeler
Nanosystems insulin oral delivery diabetes bioavailability oral peptides
Kaynakça
- 1. Choonara BF, Choonara YT, Kumar P, Bijikumar D, Du Toit LC, Pillay V. A review of advanced oral drug delivery technologies facilitating the protection and absorption of protein and peptide molecules. Biotechnol Adv 2014; 32: 1269-82. [CrossRef] 2. Hwang SR, Byun Y. Advances in oral macromolecular drug delivery. Expert Opin Drug Deliv 2014; 11: 1955-67. [CrossRef] 3. Pamnani D. Reality Check on Oral Insulin. Pharma Express 2008. 4. Fonte P, Araújo F, Reis S, Sarmento B. Oral insulin delivery: how far are we? J Diabetes Sci Technol 2013; 7: 520-31. [CrossRef] 5. Collins, CE. A Short Course in Medical Terminology. 3rd Ed. USA: Lippincott Williams & Wilkins; 2013. p.160. 6. Akalın A, Akıncı B, Atabey A, Atmaca A, Atmaca H, Aydın H, ve ark. Diabetes Mellitus 2009: Multidisipliner Yaklaşımla Tanı, Tedavi ve İzlem. 2nd Ed. İmamoğlu Ş (ed). İstanbul, Turkey: Deomed; 2009. 7. Sheehan MT. Current therapeutic options in type 2 diabetes mellitus: A practical approach. Clin Med Res 2003; 1: 189-200. [CrossRef] 8. Brange J, Langkjær. Stability and Characterization of Protein and Peptide Drugs: Case Histories. Wang YJ, Pearlman R (eds). New York: Springer Science and Business Media; 1993. p. 315-50. [CrossRef] 9. Triplitt CL, Reasner CA, Isley WL. Diabetes mellitus. In: Pharmacotherapy, A Pathophysiologic Approach. 5th Ed. Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM (eds). New York: McGraw Hill; 2002. p. 1335-67. 10. Hall JE. Guyton and Hall Textbook of Medical Physiology. 12th Ed. Philedelphia: Saunders; 2011. p. 884-98. 11. Agarwal V, Khan MA. Current status of the oral delivery of insulin. Pharm Technol 2001; 25: 76-90. 12. Fischer A. The effect of molecular size on the nasal absorption of water soluble compounds in albino rat. J Pharm Pharmacol 1987; 39: 357-62. [CrossRef] 13. Acartürk F, Ağabeyoğlu İ, Araman A, Brannon-Peppas L, Çapan Y, Çelebi N, ve ark. Ed: Zırh-Gürsoy A. Kontrollü Salım Sistemleri. 2nd Ed. İstanbul: Kontrollü Salım Sistemleri Derneği; 2014. 14. Arbit E, Kidron M. Oral Insulin: The Rationale for This Approach and Current Developments. J Diabetes Sci Technol 2009; 3: 562-7. [CrossRef] 15. Chen MC, Sonaje K, Chen KJ, Sung HW. A review of the prospects for polymeric nanoparticle platforms in oral insulin delivery. Biomaterials 2011; 32: 9826-38. [CrossRef] 16. Bruno BJ, Miller GD, Lim CS. Basics and recent advances in peptide and protein drug delivery. Ther Deliv 2013; 4: 1443-67. [CrossRef] 17. Sonia TA, Sharma CP. Oral Delivery of Insulin. Woodhead Publishing; 2014. 18. Hamman JH, Enslin GM, Kotzé AF. Oral delivery of peptide drugs: Barriers and Developments. Biodrugs 2005; 19: 165-77. [CrossRef] 19. Kinesh VP, Neelam DP, Punit BP, Bhavesh SB, Pragna KS. Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products. Int J Pharm Sci Nanotech 2010; 3: 1057-64. 20. Brayden DJ, Mrsny RJ. Oral peptide delivery: prioritizing the leading technologies. Ther Deliv 2011; 2: 1567-73. [CrossRef] 21. Muheem A, Shakeel F, Jahangir MA, Anwar M, Mallick N, Jain GK, et al. A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives. Saudi Pharm J 2016; 24: 413-28. [CrossRef] 22. Acartürk F, Alpar HO, Arıca B, Bahadori F, Badıllı U, Başaran N, ve ark. Nanofarmasötikler ve Uygulamaları. Zırh-Gürsoy A (ed). İstanbul: Kontrollü Salım Sistemleri Derneği; 2014. 23. Cho HJ, Oh J, Choo MK, Ha JI, Park Y, Maeng HJ. Chondroitin sulfate-capped gold nanoparticles for the oral delivery of insulin. Int J Biol Macromol 2014; 63: 15-20. [CrossRef] 24. Sarmento B, Ribeiro A, Veiga F, Sampaio P, Neufeld R, Ferreira D. Alginate/ chitosan nanoparticles are effective for oral insulin delivery. Pharm Res 2007; 24: 2198-206. [CrossRef] 25. Goswami S, Bajpai J, Bajpai AK. Calcium alginate nanocarriers as possible vehicles for oral delivery of insulin. J Exp Nanosci 2014; 9: 337-56. [CrossRef] 26. Reis CP, Ribeiro AJ, Houng S, Veiga F, Neufeld RJ. Nanoparticulate delivery system for insulin: Design, characterization and in vitro/in vivo bioactivity. Eur J Pharm Sci 2007; 30: 392-7. [CrossRef] 27. Hosseininasab S, Pashaei-Asi R, Khandaghi AA, Nasrabadi HT, Nejati-Koshki K, Akbarzadeh A, et al. Synthesis, characterization and in vitro studies of PLGA-PEG nanoparticles for oral insulin delivery. Chem Biol Drug Des 2014; 84: 307-15. [CrossRef] 28. Zhang Y, Wu X, Meng L, Zhang Y, Ai R, Qi N, et al. Thiolated Eudragit nanoparticles for oral insulin delivery: Preparation, characterization and in vivo evaluation. Int J Pharm 2012; 436: 341-50. [CrossRef] 29. Sheng J, He H, Han L, Qin J, Chen S, Ru G, et al. Enhancing Insulin Oral Absorption by Using Mucoadhesive Nanoparticles Loaded with LMWP-linked Insulin Conjugates. J Control Release 2016; 233: 181-90. [CrossRef] 30. Chung H, Kim JS, Um J, Kwon I, Jeong S. Self- assembled ‘nanocubicle’ as a carrier for peroral insulin delivery. Diabetologia 2002; 45: 448-51. [CrossRef] 31. Sarmento B, Martins S, Ferreira D, Souto EB. Oral insulin delivery by means of solid lipid nanoparticles. Int J Nanomedicine 2007; 2: 743-9. 32. Zhang N, Ping Q, Huang G, Xu W, Cheng Y, Han X. Lectin-modified solid lipid nanoparticles as carriers for oral administration of insulin. Int J Pharm 2006; 327: 153-9. [CrossRef] 33. Niu M, Lu Y, Hovgaard L, Guan P, Tan Y, Lian R, et al. Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: The effect of cholate type, particle size and administered dose. Eur J Pharm Biopharm 2012; 81: 265-72. [CrossRef] 34. Zhang X, Qi J, Lu Y, He W, Li X, Wu W. Biotinylated liposomes as potential carriers for the oral delivery of insulin. Nanomedicine 2014; 10: 167-76. [CrossRef] 35. Cui M, Wu W, Hovgaard L, Lu Y, Chen D, Qi J. Liposomes containing cholesterol analogues of botanical origin as drug delivery systems to enhance the oral absorption of insulin. Int J Pharm 2015; 489: 277-84. [CrossRef] 36. Moghassemi S, Parnian E, Hakamivala A, Darzianiazizi M, Vardanjani MM, Kashanian S, et al. Uptake and transport of insulin across intestinal membrane model using trimethyl chitosan coated insulin niosomes. Mat Sci Eng C 2015; 46: 333-40. [CrossRef] 37. Hans ML, Lowman AM. Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 2002; 6: 319-27. [CrossRef] 38. Ma EL, Ma H, Liu Z, Zheng CX, Duan MX. In vitro and in vivo evaluation of a novel oral insulin formulation. Acta Pharmacol Sin 2006; 27: 1382-8. [CrossRef] 39. Rao SVR, Yajurvedi K, Shao J. Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of protein drugs: III: in vivo oral absorption study. Int J Pharm 2008; 362: 16-9. [CrossRef] 40. Zhang Q, He N, Zhang L, Zhu F, Chen Q, Qin Y, et al. The in vitro and in vivo study on self-nanoemulsifying drug delivery system (SNEDDS) based on insulin-phospholipid complex. J Biomed Nanotechnol 2012; 8: 90-7. [CrossRef] 41. Li P, Tan A, Prestidge CA, Nielsen HM, Müllertz A. Self-nanoemulsifying drug delivery systems for oral insulin delivery: In vitro and in vivo evaluations of enteric coating and drug loading. Int J Pharm 2014; 477: 390-8. [CrossRef] 42. Sakloetsakun D, Dünnhaupt S, Barthelmes J, Perera G, Bernkop-Schnürch A. Combining two technologies: Multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration. Int J Biol Macromol 2013; 61: 363-72. [CrossRef] 43. Kabanov AV, Vinogradov SV. Nanogels as Pharmaceutical Carriers: Finite Networks of Infinite Capabilities. Angew Chem Int Ed Engl 2009; 48: 5418-29. [CrossRef] 44. Morishita M, Goto T, Peppas NA, Joseph JI, Torjman MC, Munsick C, et al. Mucosal insulin delivery systems based on complexation polymer hydrogels: effect of particle size on insulin enteral absorption. J Control Release 2004; 97: 115-24. [CrossRef] 45. Foss AC, Goto T, Morshita M, Peppas NA. Development of acrylic-based copolymers for oral insulin delivery. Eur J Pharm Biopharm 2004; 57: 163-9. [CrossRef] 46. Ramkissoon-Ganorkar C, Liu F, Baudys M, Kim SW. Modulating insulin-release profile from pH/thermosensitive polymeric beads through polymer molecular weight. J Control Release 1999; 59: 287-98. [CrossRef] 47. Zhao D, Shi X, Liu T, Lu X, Qiu G, Shea KJ. Synthesis of surfactant-free hydroxypropyl methylcellulose nanogels for controlled release of insulin. Carbohyd Polym 2016; 151: 1006-11. [CrossRef] 48. Wang J, Xu M, Cheng X, Kong M, Liu Y, Feng C, et al. Positive/negative surface charge of chitosan based nanogels and its potential influence on oral insulin delivery. Carbohyd Polym 2016; 136: 867-74. [CrossRef] 49. Hoare T, Pelton R. Charge-switching, amphoteric glucose-responsive microgels with physiological swelling activity. Biomacromolecules 2008; 9: 733-40. [CrossRef] 50. Kroschewski R. Molecular mechanisms of epithelial polarity: about shapes, forces and orientation problems. Physiology 2004; 19: 61-6. [CrossRef]
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Articles |
| Yazarlar | |
| Yayımlanma Tarihi | 15 Eylül 2017 |
| Gönderilme Tarihi | 21 Eylül 2016 |
| Yayımlandığı Sayı | Yıl 2017 Cilt: 7 Sayı: 3 |
Kaynak Göster
