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RECENT TECHNOLOGIES IN CONTROLLED RELEASE DRUG DELIVERY

Yıl 2022, Cilt: 5 Sayı: 2, 122 - 129, 30.06.2022
https://doi.org/10.26650/JARHS2022-1122852

Öz

Conventional drug delivery systems can be inadequate in many areas today due to limiting factors such as the narrow therapeutic window, complex dosing interval in long-term treatments, and systemic toxicity. Accordingly, a search has been carried out for new controlled drug delivery systems, which aim to localize the pharmacological activity of the drug to the desired area at the desired rate, and exhibit increased activity with less complications for more drugs. Better patient compliance can be achieved with microfluidic-based drug delivery systems, which have been developed to meet these needs, and better release control can be achieved with advanced drug applications. These systems, created by the control and manipulation of nano/micro-sized liquids, have taken their place in the controlled release platform with a unique character on a single chip.
This review provides general information about controlled drug release, then discusses biomedical devices, one of the new technologies developed through advancing research, and the microfluidic devices (micropumps and microneedles) that they utilize. Their types, structures, properties, preparation techniques, where they can be used and related applications, the advantages they can bring to controlled drug delivery, and progress made on this subject are examined, with examples.

Kaynakça

  • 1. Mainardes RM, Silva LP. Drug delivery systems: Past, present, and future. Current Drug Targets 2004;5(5):449-55. google scholar
  • 2. Davoodi P, Lee LY, Xu Q, Sunil V, Sun Y, Soh S, et al. Drug delivery systems for programmed and on-demand release. Adv Drug Deliv Rev 2018;132:104-38. google scholar
  • 3. Park K. The controlled drug delivery systems: Past forward and future back. J Control Release 2014;190:3-8. google scholar
  • 4. Sutradhar KB, Sumi CD. İmplantable microchip: The futuristic controlled drug delivery system. Drug Delivery 2016;23(1):1-11. google scholar
  • 5. Green AE, Rose PG. Pegylated liposomal doxorubicin in ovarian cancer. İnt J Nanomedicine 2006;1(3):229-39. google scholar
  • 6. Khan AN, Ermakov A, Sukhorukov G, Hao Y. Radio frequency controlled wireless drug delivery devices. Appl Phys Rev 2019;6:041301. google scholar
  • 7. Gao N, Li XJ. Controlled drug delivery using microfluidic devices. İn: Xiujun JL,Yu Z, editors. Microfluidic devices for biomedical applications. Texas: Woodhead Publishing Limited; 2013.p.165-85. google scholar
  • 8. Gowers SAN, Rogers ML, Booth MA, Leong CL, Samper İC, Phairatana T, et al. Clinical translation of microfluidic sensor devices: focus on calibration and analytical robustness. Lab Chip 2019;19:2537-48. google scholar
  • 9. Sharma S, Zapatero-Rodnguez J, Estrela P, O’Kennedy R. Point-of-care diagnostics in low resource settings: present status and future role of microfluidics. Biosensors 2015;5(3):577-01. google scholar
  • 10. Lok KS, Abdul MSZ, Lee PP, Kwok YC, Nguyen NT. Rapid determination of vitamin B12 concentration with a chemiluminescence lab on a chip. Lab Chip 2012;12(13):2353-61. google scholar
  • 11. Cui P, Wang S. Application of microfluidic chip technology in pharmaceutical analysis: A review. J Pharm Anal 2019;9(4):238-47. google scholar
  • 12. Wang Yİ, Abaci HE, Shuler ML. Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol Bioeng 2017;114(1):184-94. google scholar
  • 13. Veerla SC, Kim DR, Yang SY. Fabrication of a microfluidic device for studying the in situ drug loading/release behavior of graphene oxide encapsulated hydrogel beads. Biomater Res 2018;22(7):2-11. google scholar
  • 14. Damiati S, Kompella UB, Damiati SA, Kodzius R. Microfluidic devices for drug delivery systems and drug screening. Genes 2018;9(2):103. google scholar
  • 15. Dou M, Dominguez DC, Li X, Sanchez J, Scott G. A versatile PDMS/ paper hybrid microfluidic platform for sensitive infectious disease diagnosis. Anal Chem 2014;86(15):7978-86. google scholar
  • 16. Welch D, Christen JB. Real-time feedback control of pH within microfluidics using integrated sensing and actuation. Lab Chip 2014;14(6):1191-7. google scholar
  • 17. Sanjay ST, Dou M, Fu G, Xu F, Li X. Controlled drug delivery using microdevices. Curr Pharm Biotechnol 2016;17(9):772-87. google scholar
  • 18. Xu Q, Hashimoto M, Dang TT, Hoare T, Kohane DS, Whitesides GM, Langer R, Anderson DG. Preparation of monodisperse biodegradable polymer microparticles using a microfluidic flow-focusing device for controlled drug delivery. Small 2009;5(13):1575-81. google scholar
  • 19. Belliveau NM, Huft J, Lin PJ, Chen S, Leung AK, Leaver TJ, et al. Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Mol Ther Nucleic Acids 2012;1(8): e37. google scholar
  • 20. Torino E, Russo M, Ponsiglione AM. Lab-on-a-chip preparation routes for organic nanomaterials for drug delivery. İn: Santos HA, Liu D, Zhang H, editors. Microfluidics for pharmaceutical applications. From nano/micro systems fabrication to controlled drug delivery. Micro and nano technologies. UK: William Andrew Applied Science Publishers; 2019.p.137-53. google scholar
  • 21. Mancera-Andrade EI, Parsaeimehr A, Arevalo-Gallegos A, Ascencio-Favela G, Saldivar RP. Microfluidics technology for drug delivery: A review. Frontiers In Bioscience, Elite 2018;10(1):74-91. google scholar
  • 22. Li W, Zhang L, Ge X, Xu B, Zhang W, Qu L, et al. Microfluidic fabrication of microparticles for biomedical applications. Chem Soc Rev 2018;47(15):5646-83. google scholar
  • 23. Zhao CX. Multiphase flow microfluidics for the production of single or multiple emulsions for drug delivery. Adv Drug Delivery Rev 2013;65(11-12):1420-46. google scholar
  • 24. Yang CH, Huang KS, Chang JY. Manufacturing monodisperse chitosan microparticles containing ampicillin using a microchannel chip. Biomed Microdevices 2007;9(2):253-9. google scholar
  • 25. Xu JH, Zhao H, Lan WJ, Luo GS. A novel microfl uidic approach for monodispersed chitosan microspheres with controllable structures. Adv Healthcare Mater 2012;1(1):106-11. google scholar
  • 26. He F, Wang W, He XH, Yang XL, Li M, Xie R, et al. Controllable multicompartmental capsules with distinct cores and shells for synergistic release. ACS Appl Mater Interfaces 2016;8(13):8743-54. google scholar
  • 27. Liu D, Zhang H, Herranz-Blanco B, Makila E, Lehto VP, Salonen J, et al. Microfluidic assembly of monodisperse multistage ph-responsive polymer/porous silicon composites for precisely controlled multi-drug delivery. Small 2014;10(10):2029-38 google scholar
  • 28. Huang KS, Yang CH, Kung CP, Grumezescu AM, Ker MD, Lin YS, et al. Synthesis of uniform core-shell gelatin-alginate microparticles as intestine-released oral delivery drug carrier. Electrophoresis 2014;35(2-3):330-6. google scholar
  • 29. Chen T, Gomez-Escoda B, Munoz-Garcia J, Babic J, Griscom L, Wu PYJ, et al. A drug-compatible and temperature-controlled microfluidic device for live-cell imaging. Open Biol 2016;6(8):160156. google scholar
  • 30. Pirmorad FN, Jackson JK, Burt HM, Chiao M. A magnetically controlled MEMS device for drug delivery: Design, fabrication, and testing. Lab Chip 2011;11(18):3072-80. google scholar
  • 31. Webster A, Greenman J, Haswell SJ. Development of microfluidic devices for biomedical and clinical application. JCTB 2011;86(1):10-7. google scholar
  • 32. Cheng WC, He Y, Chang AY, Que L. A microfluidic chip for controlled release of drugs from microcapsules. Biomicrofluidics 2013;7(6):064102. google scholar
  • 33. Chaudhuri J, Timung S, Singh AK, Mandalab TK, Bandyopadhyayab D. Simulation of a microfluidic droplet driven controlled drug delivery system. In: Timung S, Chaundri J, Bhattacharjee M, Singh AK, Mandal TK, Bandyopadhyay D, Das B, Patra S, Dasari A, Majumdar SK, editors. External field induced flow morphologies of two-phase flow inside microfluidic channels. Reflux. IIT Guwahati, India; 2015.p.1-2. google scholar
  • 34. Araujo F, Shrestha N, Shahbazi MA, Liu DF, Herranz-Blanco B, Makila EM, et al. Microfluidic assembly of a multifunctional tailorable composite system designed for site specific combined oral delivery of peptide drugs. ACS Nano 2015;9(8):8291-302. google scholar
  • 35. Zhang L, Chen Q, Ma Y, Sun J. Microfluidic methods for fabrication and engineering of nanoparticle drug delivery systems. ACS Appl Bio Mater 2020;3(1):107-20. google scholar
  • 36. Karale CK, Nikumbh KK, Wagh DS, Thorat SS. Microfluidics in drug discovery: An overview. Inventi Rapid: Pharm Process Dev 2013;2013(4):1-14. google scholar
  • 37. Duncanson WJ, Lin T, Abate AR, Seiffert S, Shah RK, Weitz DA. Microfluidic synthesis of advanced microparticles for encapsulation and controlled release. Lab Chip 2012;12(12):2135-45. google scholar
  • 38. Mura S, Nicolas J, Couvreur P. Stimuli-responsive nanocarriers for drug delivery. Nature Mats 2013;12(11):991-1003. google scholar
  • 39. Pan L, He Q, Liu J, Chen Y, Ma M, Zhang L, Shi J. Nuclear-targeted drug delivery of TAT peptide-conjugated monodisperse mesoporous silica nanoparticles. J Am Chem Soc 2012;134(13):5722-5. google scholar
  • 40. Oliveira H, Perez-Andres E, Thevenot J, Sandre O, Berra E, Lecommandoux S. Magnetic field triggered drug release from polymersomes for cancer therapeutics. J Control Release 2013;169(3):165-70. google scholar
  • 41. So H, Seo YH, Pisano AP. Refillable and magnetically actuated drug delivery system using pear-shaped viscoelastic membrane. Biomicrofluidics 2014;8(4):044119. google scholar
  • 42. Kaur M, Ita KB, Popova IE, Parikh SJ, Bair DA. Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate. Eur J Pharm Biopharm 2014;86(2):284-91. google scholar
  • 43. Kim YC, Edelhauser HF, Prausnitz MR. Intracorneal delivery of bevacizumab using microneedles to treat injury-induced neovascularization. Invest Ophthalmol Vis Sci 2014;55(11): 737686. google scholar
  • 44. Jun H, Han MR, Kang NG, Park JH, Park JH. Use of hollow microneedles for targeted delivery of phenylephrine to treat fecal incontinence. J Control Release 2015;207:1-6 google scholar
  • 45. Yan XX, Liu JQ, Jiang SD, Yang B, Yang CS. Fabrication and testing of porous Ti microneedles for drug delivery. Micro Nano Lett 2013;8(12):906-8. google scholar
  • 46. Sullivan SP, Koutsonanos DG, Martin MP, Lee JW, Zarnitsyn V, Murthy N, et al. Dissolving polymer microneedle patches for influenza vaccination. Nat Med 2010;16(8):915-20. google scholar
  • 47. Fitzpatrick D. Implantable Electronic Medical Devices. 1th ed. London: Academic press; 2015. google scholar
  • 48. Villarruel Mendoza LA, Scilletta NA, Bellino MG, Desimone MF, Catalano PN. Recent advances in micro-electro-mechanical devices for controlled drug release applications. Front Bioeng Biotechnol 2020;8:827. google scholar

KONTROLLÜ İLAÇ SALIMINDA SON TEKNOLOJİLER

Yıl 2022, Cilt: 5 Sayı: 2, 122 - 129, 30.06.2022
https://doi.org/10.26650/JARHS2022-1122852

Öz

Konvansiyonel ilaç salım sistemleri dar terapötik pencere, uzun dönem tedavilerdeki kompleks dozlama aralığı ve sistemik toksisite gibi kısıtlayıcı faktörlerle günümüzde pek çok alanda yetersiz kalabilmektedir. Buna istinaden, ilacın farmakolojik aktivitesini istenilen oranda, istenen bölgeye lokalize etmeyi amaçlayan ve daha çok ilaç için daha az komplikasyonla artırılmış aktivite sergileyen yeni kontrollü ilaç salım sistemleri arayışına gidilmiştir. Bu ihtiyaçları karşılamak üzere geliştirilen mikroakışkan bazlı ilaç salım sistemleri ile daha iyi hasta uyuncu sağlanabilmekte, gelişmiş ilaç uygulamaları ile daha iyi salım kontrollü oluşturulabilmektedir. Nano/ mikro boyuttaki sıvıların kontrolü ve manüplasyonu ile oluşturulan bu sistemler tek bir çip üzerinde eşsiz bir karakterle kontrollü salım platformunda yerini almıştır.
Bu derlemede kontrollü ilaç salımı hakkında genel bir değerlendirmeden sonra ilerleyen araştırmalarla gelişen yeni teknolojilerden biyomedikal cihazlar ve bunlar arasında bulunan mikroakışkan bazlı cihazlar, mikropompalar, mikroiğneler konu edilmiştir. Bunların çeşitleri, yapısı, özellikleri, hazırlanma teknikleri, türleri, nerelerde kullanılabileceği ve ilişkili uygulamalar, kontrollü ilaç salımına getirebilecekleri avantajlar, bu konudaki ilerlemeler örneklerle incelenmiştir.

Kaynakça

  • 1. Mainardes RM, Silva LP. Drug delivery systems: Past, present, and future. Current Drug Targets 2004;5(5):449-55. google scholar
  • 2. Davoodi P, Lee LY, Xu Q, Sunil V, Sun Y, Soh S, et al. Drug delivery systems for programmed and on-demand release. Adv Drug Deliv Rev 2018;132:104-38. google scholar
  • 3. Park K. The controlled drug delivery systems: Past forward and future back. J Control Release 2014;190:3-8. google scholar
  • 4. Sutradhar KB, Sumi CD. İmplantable microchip: The futuristic controlled drug delivery system. Drug Delivery 2016;23(1):1-11. google scholar
  • 5. Green AE, Rose PG. Pegylated liposomal doxorubicin in ovarian cancer. İnt J Nanomedicine 2006;1(3):229-39. google scholar
  • 6. Khan AN, Ermakov A, Sukhorukov G, Hao Y. Radio frequency controlled wireless drug delivery devices. Appl Phys Rev 2019;6:041301. google scholar
  • 7. Gao N, Li XJ. Controlled drug delivery using microfluidic devices. İn: Xiujun JL,Yu Z, editors. Microfluidic devices for biomedical applications. Texas: Woodhead Publishing Limited; 2013.p.165-85. google scholar
  • 8. Gowers SAN, Rogers ML, Booth MA, Leong CL, Samper İC, Phairatana T, et al. Clinical translation of microfluidic sensor devices: focus on calibration and analytical robustness. Lab Chip 2019;19:2537-48. google scholar
  • 9. Sharma S, Zapatero-Rodnguez J, Estrela P, O’Kennedy R. Point-of-care diagnostics in low resource settings: present status and future role of microfluidics. Biosensors 2015;5(3):577-01. google scholar
  • 10. Lok KS, Abdul MSZ, Lee PP, Kwok YC, Nguyen NT. Rapid determination of vitamin B12 concentration with a chemiluminescence lab on a chip. Lab Chip 2012;12(13):2353-61. google scholar
  • 11. Cui P, Wang S. Application of microfluidic chip technology in pharmaceutical analysis: A review. J Pharm Anal 2019;9(4):238-47. google scholar
  • 12. Wang Yİ, Abaci HE, Shuler ML. Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol Bioeng 2017;114(1):184-94. google scholar
  • 13. Veerla SC, Kim DR, Yang SY. Fabrication of a microfluidic device for studying the in situ drug loading/release behavior of graphene oxide encapsulated hydrogel beads. Biomater Res 2018;22(7):2-11. google scholar
  • 14. Damiati S, Kompella UB, Damiati SA, Kodzius R. Microfluidic devices for drug delivery systems and drug screening. Genes 2018;9(2):103. google scholar
  • 15. Dou M, Dominguez DC, Li X, Sanchez J, Scott G. A versatile PDMS/ paper hybrid microfluidic platform for sensitive infectious disease diagnosis. Anal Chem 2014;86(15):7978-86. google scholar
  • 16. Welch D, Christen JB. Real-time feedback control of pH within microfluidics using integrated sensing and actuation. Lab Chip 2014;14(6):1191-7. google scholar
  • 17. Sanjay ST, Dou M, Fu G, Xu F, Li X. Controlled drug delivery using microdevices. Curr Pharm Biotechnol 2016;17(9):772-87. google scholar
  • 18. Xu Q, Hashimoto M, Dang TT, Hoare T, Kohane DS, Whitesides GM, Langer R, Anderson DG. Preparation of monodisperse biodegradable polymer microparticles using a microfluidic flow-focusing device for controlled drug delivery. Small 2009;5(13):1575-81. google scholar
  • 19. Belliveau NM, Huft J, Lin PJ, Chen S, Leung AK, Leaver TJ, et al. Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Mol Ther Nucleic Acids 2012;1(8): e37. google scholar
  • 20. Torino E, Russo M, Ponsiglione AM. Lab-on-a-chip preparation routes for organic nanomaterials for drug delivery. İn: Santos HA, Liu D, Zhang H, editors. Microfluidics for pharmaceutical applications. From nano/micro systems fabrication to controlled drug delivery. Micro and nano technologies. UK: William Andrew Applied Science Publishers; 2019.p.137-53. google scholar
  • 21. Mancera-Andrade EI, Parsaeimehr A, Arevalo-Gallegos A, Ascencio-Favela G, Saldivar RP. Microfluidics technology for drug delivery: A review. Frontiers In Bioscience, Elite 2018;10(1):74-91. google scholar
  • 22. Li W, Zhang L, Ge X, Xu B, Zhang W, Qu L, et al. Microfluidic fabrication of microparticles for biomedical applications. Chem Soc Rev 2018;47(15):5646-83. google scholar
  • 23. Zhao CX. Multiphase flow microfluidics for the production of single or multiple emulsions for drug delivery. Adv Drug Delivery Rev 2013;65(11-12):1420-46. google scholar
  • 24. Yang CH, Huang KS, Chang JY. Manufacturing monodisperse chitosan microparticles containing ampicillin using a microchannel chip. Biomed Microdevices 2007;9(2):253-9. google scholar
  • 25. Xu JH, Zhao H, Lan WJ, Luo GS. A novel microfl uidic approach for monodispersed chitosan microspheres with controllable structures. Adv Healthcare Mater 2012;1(1):106-11. google scholar
  • 26. He F, Wang W, He XH, Yang XL, Li M, Xie R, et al. Controllable multicompartmental capsules with distinct cores and shells for synergistic release. ACS Appl Mater Interfaces 2016;8(13):8743-54. google scholar
  • 27. Liu D, Zhang H, Herranz-Blanco B, Makila E, Lehto VP, Salonen J, et al. Microfluidic assembly of monodisperse multistage ph-responsive polymer/porous silicon composites for precisely controlled multi-drug delivery. Small 2014;10(10):2029-38 google scholar
  • 28. Huang KS, Yang CH, Kung CP, Grumezescu AM, Ker MD, Lin YS, et al. Synthesis of uniform core-shell gelatin-alginate microparticles as intestine-released oral delivery drug carrier. Electrophoresis 2014;35(2-3):330-6. google scholar
  • 29. Chen T, Gomez-Escoda B, Munoz-Garcia J, Babic J, Griscom L, Wu PYJ, et al. A drug-compatible and temperature-controlled microfluidic device for live-cell imaging. Open Biol 2016;6(8):160156. google scholar
  • 30. Pirmorad FN, Jackson JK, Burt HM, Chiao M. A magnetically controlled MEMS device for drug delivery: Design, fabrication, and testing. Lab Chip 2011;11(18):3072-80. google scholar
  • 31. Webster A, Greenman J, Haswell SJ. Development of microfluidic devices for biomedical and clinical application. JCTB 2011;86(1):10-7. google scholar
  • 32. Cheng WC, He Y, Chang AY, Que L. A microfluidic chip for controlled release of drugs from microcapsules. Biomicrofluidics 2013;7(6):064102. google scholar
  • 33. Chaudhuri J, Timung S, Singh AK, Mandalab TK, Bandyopadhyayab D. Simulation of a microfluidic droplet driven controlled drug delivery system. In: Timung S, Chaundri J, Bhattacharjee M, Singh AK, Mandal TK, Bandyopadhyay D, Das B, Patra S, Dasari A, Majumdar SK, editors. External field induced flow morphologies of two-phase flow inside microfluidic channels. Reflux. IIT Guwahati, India; 2015.p.1-2. google scholar
  • 34. Araujo F, Shrestha N, Shahbazi MA, Liu DF, Herranz-Blanco B, Makila EM, et al. Microfluidic assembly of a multifunctional tailorable composite system designed for site specific combined oral delivery of peptide drugs. ACS Nano 2015;9(8):8291-302. google scholar
  • 35. Zhang L, Chen Q, Ma Y, Sun J. Microfluidic methods for fabrication and engineering of nanoparticle drug delivery systems. ACS Appl Bio Mater 2020;3(1):107-20. google scholar
  • 36. Karale CK, Nikumbh KK, Wagh DS, Thorat SS. Microfluidics in drug discovery: An overview. Inventi Rapid: Pharm Process Dev 2013;2013(4):1-14. google scholar
  • 37. Duncanson WJ, Lin T, Abate AR, Seiffert S, Shah RK, Weitz DA. Microfluidic synthesis of advanced microparticles for encapsulation and controlled release. Lab Chip 2012;12(12):2135-45. google scholar
  • 38. Mura S, Nicolas J, Couvreur P. Stimuli-responsive nanocarriers for drug delivery. Nature Mats 2013;12(11):991-1003. google scholar
  • 39. Pan L, He Q, Liu J, Chen Y, Ma M, Zhang L, Shi J. Nuclear-targeted drug delivery of TAT peptide-conjugated monodisperse mesoporous silica nanoparticles. J Am Chem Soc 2012;134(13):5722-5. google scholar
  • 40. Oliveira H, Perez-Andres E, Thevenot J, Sandre O, Berra E, Lecommandoux S. Magnetic field triggered drug release from polymersomes for cancer therapeutics. J Control Release 2013;169(3):165-70. google scholar
  • 41. So H, Seo YH, Pisano AP. Refillable and magnetically actuated drug delivery system using pear-shaped viscoelastic membrane. Biomicrofluidics 2014;8(4):044119. google scholar
  • 42. Kaur M, Ita KB, Popova IE, Parikh SJ, Bair DA. Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate. Eur J Pharm Biopharm 2014;86(2):284-91. google scholar
  • 43. Kim YC, Edelhauser HF, Prausnitz MR. Intracorneal delivery of bevacizumab using microneedles to treat injury-induced neovascularization. Invest Ophthalmol Vis Sci 2014;55(11): 737686. google scholar
  • 44. Jun H, Han MR, Kang NG, Park JH, Park JH. Use of hollow microneedles for targeted delivery of phenylephrine to treat fecal incontinence. J Control Release 2015;207:1-6 google scholar
  • 45. Yan XX, Liu JQ, Jiang SD, Yang B, Yang CS. Fabrication and testing of porous Ti microneedles for drug delivery. Micro Nano Lett 2013;8(12):906-8. google scholar
  • 46. Sullivan SP, Koutsonanos DG, Martin MP, Lee JW, Zarnitsyn V, Murthy N, et al. Dissolving polymer microneedle patches for influenza vaccination. Nat Med 2010;16(8):915-20. google scholar
  • 47. Fitzpatrick D. Implantable Electronic Medical Devices. 1th ed. London: Academic press; 2015. google scholar
  • 48. Villarruel Mendoza LA, Scilletta NA, Bellino MG, Desimone MF, Catalano PN. Recent advances in micro-electro-mechanical devices for controlled drug release applications. Front Bioeng Biotechnol 2020;8:827. google scholar
Toplam 48 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Eczacılık ve İlaç Bilimleri
Bölüm Derleme
Yazarlar

Esher Özçelik 0000-0002-5611-1143

Meryem Sedef Erdal 0000-0001-6220-2036

Yıldız Özsoy 0000-0002-9110-3704

Yayımlanma Tarihi 30 Haziran 2022
Gönderilme Tarihi 29 Mayıs 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 5 Sayı: 2

Kaynak Göster

MLA Özçelik, Esher vd. “KONTROLLÜ İLAÇ SALIMINDA SON TEKNOLOJİLER”. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, c. 5, sy. 2, 2022, ss. 122-9, doi:10.26650/JARHS2022-1122852.