A review of preparation methods and biomedical applications of poly(ε-caprolactone)-based novel formulations

1. Osi B, Khoder M, Al-Kinani AA, Alany RG (2022) Pharmaceutical, biomedical and ophthalmic applications of biodegradable polymers (BDPs): literature and patent review. Pharm Dev Technol 27(3):341–356. https://doi.org/10.1080/10837450.2022.205506310.1080/10837450.2022.2055063 ↗

2. Dash TK, Konkimalla VB (2012) Poly-є-caprolactone based formulations for drug delivery and tissue engineering: a review. J Control Release 158(1):15–33. https://doi.org/10.1016/j.jconrel.2011.09.06410.1016/j.jconrel.2011.09.064 ↗

3. Song R, Murphy M, Li C, Ting K, Soo C, Zheng Z (2018) Current development of biodegradable polymeric materials for biomedical applications. Drug Des Dev Ther 12:3117–3145. https://doi.org/10.2147/dddt.S16544010.2147/dddt.S165440 ↗

4. Manavitehrani I, Fathi A, Badr H, Daly S, Negahi Shirazi A, Dehghani F (2016) Biomedical applications of biodegradable polyesters. Polymers 8(1):20. https://doi.org/10.3390/polym801002010.3390/polym8010020 ↗

5. Dash T, Konkimalla VB (2012) Polymeric modification and its implication in drug delivery: poly-ε-caprolactone (PCL) as a model polymer. Mol Pharm 9:2365–2379. https://doi.org/10.1021/mp300195210.1021/mp3001952 ↗

6. Darie-Niță RN, Râpă M, Frąckowiak S (2022) Special features of polyester-based materials for medical applications. Polymers. https://doi.org/10.3390/polym1405095110.3390/polym14050951 ↗

7. Labet M, Thielemans W (2009) Synthesis of polycaprolactone: a review. Chem Soc Rev 38(12):3484–3504. https://doi.org/10.1039/b820162p10.1039/b820162p ↗

8. Laffleur F, Keckeis V (2020) Advances in drug delivery systems: work in progress still needed? Int J Pharm 590:119912. https://doi.org/10.1016/j.ijpharm.2020.11991210.1016/j.ijpharm.2020.119912 ↗

9. Adepu S, Ramakrishna S (2021) Controlled drug delivery systems: current status and future directions. Molecules 26(19):5905. https://doi.org/10.3390/molecules2619590510.3390/molecules26195905 ↗

10. Sung YK, Kim SW (2020) Recent advances in polymeric drug delivery systems. Biomater Res 24:12. https://doi.org/10.1186/s40824-020-00190-710.1186/s40824-020-00190-7 ↗

11. Sowmya B, Hemavathi AB, Panda PK (2021) Poly (ε-caprolactone)-based electrospun nano-featured substrate for tissue engineering applications: a review. Prog Biomater 10(2):91–117. https://doi.org/10.1007/s40204-021-00157-410.1007/s40204-021-00157-4 ↗

12. Brugmans MCP, Sӧntjens SHM, Cox MAJ, Nandakumar A, Bosman AW, Mes T, Janssen HM, Bouten CVC, Baaijens FPT, Driessen-Mol A (2015) Hydrolytic and oxidative degradation of electrospun supramolecular biomaterials in vitro degradation pathways. Acta Biomater 27:21–31. https://doi.org/10.1016/j.actbio.2015.08.03410.1016/j.actbio.2015.08.034 ↗

13. Jun I, Han HS, Edwards JR, Jeon H (2018) Electrospun fibrous scaffolds for tissue engineering: viewpoints on architecture and fabrication. Int J Mol Sci 19(3):745. https://doi.org/10.3390/ijms1903074510.3390/ijms19030745 ↗

14. Augustine R, Hasan A, Patan NK, Augustine A, Dalvi YB, Varghese R, Unni RN, Kalarikkal N, Al Moustafa AE, Thomas S (2019) Titanium nanorods loaded PCL meshes with enhanced blood vessel formation and cell migration for wound dressing applications. Macromol Biosci 19(7):e1900058. https://doi.org/10.1002/mabi.20190005810.1002/mabi.201900058 ↗

15. Raina N, Pahwa R, Khosla JK, Gupta PN, Gupta M (2022) Polycaprolactone-based materials in wound healing applications. Polym Bull 79(9):7041–7063. https://doi.org/10.1007/s00289-021-03865-w10.1007/s00289-021-03865-w ↗

16. Bartnikowski M, Dargaville TR, Ivanovski S, Hutmacher DW (2019) Degradation mechanisms of polycaprolactone in the context of chemistry, geometry and environment. Prog Polym Sci 96:1–20. https://doi.org/10.1016/j.progpolymsci.2019.05.00410.1016/j.progpolymsci.2019.05.004 ↗

17. Sun H, Mei L, Song C, Cui X, Wang P (2006) The in vivo degradation, absorption and excretion of PCL-based implant. Biomaterials 27(9):1735–1740. https://doi.org/10.1016/j.biomaterials.2005.09.01910.1016/j.biomaterials.2005.09.019 ↗

18. Pitt CG, Chasalow FI, Hibionada YM, Klimas DM, Schindler A (1981) Aliphatic polyesters. I. The degradation of poly(ϵ-caprolactone) in vivo. J Appl Polym Sci 26(11):3779–3787. https://doi.org/10.1002/app.1981.07026112410.1002/app.1981.070261124 ↗

19. Pawar R, Pathan A, Nagaraj S, Kapare H, Giram P, Wavhale R (2023) Polycaprolactone and its derivatives for drug delivery. Polym Adv Technol 34(10):3296–3316. https://doi.org/10.1002/pat.614010.1002/pat.6140 ↗

20. Wang H, Tong D, Wang L, Chen L, Yu N, Li Z (2017) A facile strategy for fabricating PCL/PEG block copolymer with excellent enzymatic degradation. Polym Degrad Stab 140:64–73. https://doi.org/10.1016/j.polymdegradstab.2017.04.01510.1016/j.polymdegradstab.2017.04.015 ↗

21. Abdelfatah J, Paz R, Alemán-Domínguez ME, Monzón M, Donate R, Winter G (2021) Experimental analysis of the enzymatic degradation of polycaprolactone: microcrystalline cellulose composites and numerical method for the prediction of the degraded geometry. Materials (Basel) 14(9):2460. https://doi.org/10.3390/ma1409246010.3390/ma14092460 ↗

22. Lykins WR, Bernards DA, Schlesinger EB, Wisniewski K, Desai TA (2022) Tuning polycaprolactone degradation for long acting implantables. Polymer 262:125473. https://doi.org/10.1016/j.polymer.2022.12547310.1016/j.polymer.2022.125473 ↗

23. França D, Morais D, Bezerra E, Araujo E, Wellen R (2018) Photodegradation mechanisms on poly(ε-caprolactone) (PCL). Mater Res. https://doi.org/10.1590/1980-5373-mr-2017-083710.1590/1980-5373-mr-2017-0837 ↗

24. Shen J, Yuan W, Badv M, Moshaverinia A, Weiss PS (2023) Modified poly(ε-caprolactone) with tunable degradability and improved biofunctionality for regenerative medicine. ACS Mater Au 3(5):540–547. https://doi.org/10.1021/acsmaterialsau.3c0002710.1021/acsmaterialsau.3c00027 ↗

25. Azari A, Golchin A, Mahmoodinia Maymand M, Mansouri F, Ardeshirylajimi A (2022) Electrospun polycaprolactone nanofibers: current research and applications in biomedical application. Adv Pharm Bull 12(4):658–672. https://doi.org/10.34172/apb.2022.07010.34172/apb.2022.070 ↗

26. Mokhena TC, Chabalala MB, Mapukata S, Mtibe A, Hlekelele L, Cele Z, Mochane MJ, Ntsendwana B, Nhlapo TA, Mokoena TP, Bambo MF, Matabola KP, Ray SS, Sadiku ER, Shingange K (2024) Electrospun PCL-based materials for health-care applications: an overview. Macromol Mater Eng. https://doi.org/10.1002/mame.20230038810.1002/mame.202300388 ↗

27. Joseph B, Augustine R, Kalarikkal N, Thomas S, Seantier B, Grohens Y (2019) Recent advances in electrospun polycaprolactone based scaffolds for wound healing and skin bioengineering applications. Mater Today Commun 19:319–335. https://doi.org/10.1016/j.mtcomm.2019.02.00910.1016/j.mtcomm.2019.02.009 ↗

28. Mochane MJ, Motsoeneng TS, Sadiku ER, Mokhena TC, Sefadi JS (2019) Morphology and properties of electrospun PCL and its composites for medical applications: a mini review. Appl Sci 9(11):220510.3390/app9112205 ↗

29. Xiao L, Wu M, Yan F, Xie Y, Liu Z, Huang H, Yang Z, Yao S, Cai L (2021) A radial 3D polycaprolactone nanofiber scaffold modified by biomineralization and silk fibroin coating promote bone regeneration in vivo. Int J Biol Macromol 172:19–29. https://doi.org/10.1016/j.ijbiomac.2021.01.03610.1016/j.ijbiomac.2021.01.036 ↗

30. Permyakova ES, Kiryukhantsev-Korneev PV, Gudz KY, Konopatsky AS, Polčak J, Zhitnyak IY, Gloushankova NA, Shtansky DV, Manakhov AM (2019) Comparison of different approaches to surface functionalization of biodegradable polycaprolactone scaffolds. Nanomaterials 9(12):1769. https://doi.org/10.3390/nano912176910.3390/nano9121769 ↗

31. Coudane J, Nottelet B, Mouton J, Garric X, Van Den Berghe H (2022) Poly(ε-caprolactone)-based graft copolymers: synthesis methods and applications in the biomedical field: a review. Molecules 27(21):7339. https://doi.org/10.3390/molecules2721733910.3390/molecules27217339 ↗

32. Wang JL, Du XJ, Yang JX, Shen S, Li HJ, Luo YL, Iqbal S, Xu CF, Ye XD, Cao J, Wang J (2018) The effect of surface poly(ethylene glycol) length on in vivo drug delivery behaviors of polymeric nanoparticles. Biomaterials 182:104–113. https://doi.org/10.1016/j.biomaterials.2018.08.02210.1016/j.biomaterials.2018.08.022 ↗

33. Patrício T, Bártolo P (2013) Thermal stability of PCL/PLA blends produced by physical blending process. Procedia Eng 59:292–297. https://doi.org/10.1016/j.proeng.2013.05.12410.1016/j.proeng.2013.05.124 ↗

34. Abdellah S (2016) Mechanical and thermal properties of promising polymer composites for food packaging applications. IOP Conf Ser Mater Sci Eng 137:012035. https://doi.org/10.1088/1757-899X/137/1/01203510.1088/1757-899X/137/1/012035 ↗

35. Chanda A, Adhikari J, Ghosh A, Chowdhury SR, Thomas S, Datta P, Saha P (2018) Electrospun chitosan/polycaprolactone-hyaluronic acid bilayered scaffold for potential wound healing applications. Int J Biol Macromol 116:774–785. https://doi.org/10.1016/j.ijbiomac.2018.05.09910.1016/j.ijbiomac.2018.05.099 ↗

36. Ehtesabi H, Massah F (2021) Improvement of hydrophilicity and cell attachment of polycaprolactone scaffolds using green synthesized carbon dots. Mater Today Sustain 13:100075. https://doi.org/10.1016/j.mtsust.2021.10007510.1016/j.mtsust.2021.100075 ↗

37. Sousa I, Mendes A, Pereira RF, Bártolo PJ (2014) Collagen surface modified poly(ε-caprolactone) scaffolds with improved hydrophilicity and cell adhesion properties. Mater Lett 134:263–267. https://doi.org/10.1016/j.matlet.2014.06.13210.1016/j.matlet.2014.06.132 ↗

38. Yaseri R, Fadaie M, Mirzaei E, Samadian H, Ebrahiminezhad A (2023) Surface modification of polycaprolactone nanofibers through hydrolysis and aminolysis: a comparative study on structural characteristics, mechanical properties, and cellular performance. Sci Rep 13(1):9434. https://doi.org/10.1038/s41598-023-36563-w10.1038/s41598-023-36563-w ↗

39. Ivanova AA, Syromotina DS, Shkarina Svetlana N, Shkarin R, Cecilia A, Weinhardt V, Baumbach T, Saveleva MS, Gorin DA, Douglas TEL, Parakhonskiy BV, Skirtach AG, Cools P, De Geyter N, Morent R, Oehr C, Surmeneva MA, Surmenev RA (2018) Effect of low-temperature plasma treatment of electrospun polycaprolactone fibrous scaffolds on calcium carbonate mineralisation. RSC Adv 8(68):39106–39114. https://doi.org/10.1039/C8RA07386D10.1039/C8RA07386D ↗

40. Qin X, Wu Y, Liu S, Yang L, Yuan H, Cai S, Flesch J, Li Z, Tang Y, Li X, Zhuang Y, You C, Liu C, Yu C (2021) Surface modification of polycaprolactone scaffold with improved biocompatibility and controlled growth factor release for enhanced stem cell differentiation. Front Bioeng Biotechnol 9:802311. https://doi.org/10.3389/fbioe.2021.80231110.3389/fbioe.2021.802311 ↗

41. Sivan M, Madheswaran D, Asadian M, Cools P, Thukkaram M, Van Der Voort P, Morent R, De Geyter N, Lukas D (2020) Plasma treatment effects on bulk properties of polycaprolactone nanofibrous mats fabricated by uncommon AC electrospinning: a comparative study. Surf Coat Tech 399:126203. https://doi.org/10.1016/j.surfcoat.2020.12620310.1016/j.surfcoat.2020.126203 ↗

42. Moraczewski K, Stepczyńska M, Malinowski R, Rytlewski P, Jagodziński B, Żenkiewicz M (2016) Stability studies of plasma modification effects of polylactide and polycaprolactone surface layers. Appl Surf Sci 377:228–237. https://doi.org/10.1016/j.apsusc.2016.03.17110.1016/j.apsusc.2016.03.171 ↗

43. Lam C, Teoh H, Hutmacher D (2007) Comparison of the degradation of polycaprolactone and polycaprolactone–(β-tricalcium phosphate) scaffolds in alkaline medium. Polym Int 56:718–728. https://doi.org/10.1002/pi.219510.1002/pi.2195 ↗

44. Thangunpai K, Hu D, Su X, Kajiyama M, Neves MA, Enomae T (2022) Thermal stability of polycaprolactone grafted densely with maleic anhydride analysed using the coats–redfern equation. Polymers 14(19):4100. https://doi.org/10.3390/polym1419410010.3390/polym14194100 ↗

45. Ge J, Li M, Zhang Q, Yang C, Wooley P, Chen X, Yang S-Y (2013) Silica aerogel improves the biocompatibility in a poly-ε-caprolactone composite used as a tissue engineering scaffold. Int J Polym Sci 2013:1–7. https://doi.org/10.1155/2013/40285910.1155/2013/402859 ↗

46. Renkler NZ, Ergene E, Gokyer S, Tuzlakoglu Ozturk M, Yilgor Huri P, Tuzlakoglu K (2021) Facile modification of polycaprolactone nanofibers with egg white protein. J Mater Sci Mater Med 32(4):34. https://doi.org/10.1007/s10856-021-06505-x10.1007/s10856-021-06505-x ↗

47. Daristotle JL, Erdi M, Lau LW, Zaki ST, Srinivasan P, Balabhadrapatruni M, Ayyub OB, Sandler AD, Kofinas P (2021) Biodegradable, tissue adhesive polyester blends for safe, complete wound healing. ACS Biomater Sci Eng 7(8):3908–3916. https://doi.org/10.1021/acsbiomaterials.1c0086510.1021/acsbiomaterials.1c00865 ↗

48. Mahoney C, Conklin D, Waterman J, Sankar J, Bhattarai N (2016) Electrospun nanofibers of poly(ε-caprolactone)/depolymerized chitosan for respiratory tissue engineering applications. J Biomater Sci Polym Ed 27(7):611–625. https://doi.org/10.1080/09205063.2016.114445410.1080/09205063.2016.1144454 ↗

49. Hu Y, Feng B, Zhang W, Yan C, Yao Q, Shao C, Yu F, Li F, Fu Y (2019) Electrospun gelatin/PCL and collagen/PCL scaffolds for modulating responses of bone marrow endothelial progenitor cells. Exp Ther Med 17(5):3717–3726. https://doi.org/10.3892/etm.2019.738710.3892/etm.2019.7387 ↗

50. Zielińska A, Carreiró F, Oliveira AM, Neves A, Pires B, Venkatesh DN, Durazzo A, Lucarini M, Eder P, Silva AM, Santini A, Souto EB (2020) Polymeric nanoparticles: production, characterization, toxicology and ecotoxicology. Molecules 25(16):3731. https://doi.org/10.3390/molecules2516373110.3390/molecules25163731 ↗

51. Chang D, Ma Y, Xu X, Xie J, Ju S (2021) Stimuli-responsive polymeric nanoplatforms for cancer therapy. Front Bioeng Biotechnol 9:707319. https://doi.org/10.3389/fbioe.2021.70731910.3389/fbioe.2021.707319 ↗

52. Crucho CIC, Barros MT (2017) Polymeric nanoparticles: a study on the preparation variables and characterization methods. Mater Sci Eng C Mater Biol Appl 80:771–784. https://doi.org/10.1016/j.msec.2017.06.00410.1016/j.msec.2017.06.004 ↗

53. Greatti VR, Oda F, Sorrechia R, Kapp BR, Seraphim CM, Weckwerth A, Chorilli M, Silva PBD, Eloy JO, Kogan MJ, Morales JO, Pietro R (2020) Poly-ε-caprolactone nanoparticles loaded with 4-nerolidylcatechol (4-nc) for growth inhibition of microsporum canis. Antibiotics (Basel) 9(12):894. https://doi.org/10.3390/antibiotics912089410.3390/antibiotics9120894 ↗

54. Kurd M, Sadegh Malvajerd S, Rezaee S, Hamidi M, Derakhshandeh K (2019) Oral delivery of indinavir using mPEG-PCL nanoparticles: preparation, optimization, cellular uptake, transport and pharmacokinetic evaluation. Artif Cells Nanomed Biotechnol 47(1):2123–2133. https://doi.org/10.1080/21691401.2019.161655310.1080/21691401.2019.1616553 ↗

55. Peng W, Jiang XY, Zhu Y, Omari-Siaw E, Deng WW, Yu JN, Xu XM, Zhang WM (2015) Oral delivery of capsaicin using MPEG-PCL nanoparticles. Acta Pharmacol Sin 36(1):139–148. https://doi.org/10.1038/aps.2014.11310.1038/aps.2014.113 ↗

56. Brzeziński M, Socka M, Makowski T, Kost B, Cieślak M, Królewska-Golińska K (2021) Microfluidic-assisted nanoprecipitation of biodegradable nanoparticles composed of PTMC/PCL (co)polymers, tannic acid and doxorubicin for cancer treatment. Colloids Surf B Biointerfaces 201:111598. https://doi.org/10.1016/j.colsurfb.2021.11159810.1016/j.colsurfb.2021.111598 ↗

57. Känkänen V, Fernandes M, Liu Z, Seitsonen J, Hirvonen SP, Ruokolainen J, Pinto JF, Hirvonen J, Balasubramanian V, Santos HA (2023) Microfluidic preparation and optimization of sorafenib-loaded poly(ethylene glycol-block-caprolactone) nanoparticles for cancer therapy applications. J Colloid Interface Sci 633:383–395. https://doi.org/10.1016/j.jcis.2022.11.12410.1016/j.jcis.2022.11.124 ↗

58. Cao Y, Wang B, Wang Y, Lou D (2014) Polymer-controlled core–shell nanoparticles: a novel strategy for sequential drug release. RSC Adv 4(57):30430–30439. https://doi.org/10.1039/C4RA03610G10.1039/C4RA03610G ↗

59. Varan C, Wickström H, Sandler N, Aktaş Y, Bilensoy E (2017) Inkjet printing of antiviral PCL nanoparticles and anticancer cyclodextrin inclusion complexes on bioadhesive film for cervical administration. Int J Pharm 531(2):701–713. https://doi.org/10.1016/j.ijpharm.2017.04.03610.1016/j.ijpharm.2017.04.036 ↗

60. Liu Y, Yang G, Hui Y, Ranaweera S, Zhao C-X (2022) Microfluidic nanoparticles for drug delivery. Small 18(36):2106580. https://doi.org/10.1002/smll.20210658010.1002/smll.202106580 ↗

61. Niculescu AG, Mihaiescu DE, Grumezescu AM (2022) A review of microfluidic experimental designs for nanoparticle synthesis. Int J Mol Sci 23(15):8293. https://doi.org/10.3390/ijms2315829310.3390/ijms23158293 ↗

62. Zimmermann R, Leal BBJ, Braghirolli DI, Pranke P (2023) Production of nanostructured systems: main and innovative techniques. Drug Discovery Today 28(2):103454. https://doi.org/10.1016/j.drudis.2022.10345410.1016/j.drudis.2022.103454 ↗

63. Arakawa CK, DeForest CA (2017) Chapter 19 - Polymer design and development. In: Vishwakarma A, Karp JM (eds) Biology and engineering of stem cell niches. Academic Press, Boston, pp 295–31410.1016/B978-0-12-802734-9.00019-6 ↗

64. Mansour HM, Sohn M, Al-Ghananeem A, Deluca PP (2010) Materials for pharmaceutical dosage forms: molecular pharmaceutics and controlled release drug delivery aspects. Int J Mol Sci 11(9):3298–3322. https://doi.org/10.3390/ijms1109329810.3390/ijms11093298 ↗

65. Lucena PA, Nascimento TL, Gaeti MPN, de Ávila RI, Mendes LP, Vieira MS, Fabrini D, Amaral AC, Lima EM (2018) In vivo vaginal fungal load reduction after treatment with itraconazole-loaded polycaprolactone-nanoparticles. J Biomed Nanotechnol 14(7):1347–1358. https://doi.org/10.1166/jbn.2018.257410.1166/jbn.2018.2574 ↗

66. Gomes MLS, da Silva NN, Borsato DM, Pretes AP, Nadal JM, Novatski A, Gomes RZ, Fernandes D, Farago PV, Zanin SMW (2019) Long-lasting anti-platelet activity of cilostazol from poly(ε-caprolactone)-poly(ethylene glycol) blend nanocapsules. Mater Sci Eng C Mater Biol Appl 94:694–702. https://doi.org/10.1016/j.msec.2018.10.02910.1016/j.msec.2018.10.029 ↗

67. Guo F, Guo D, Zhang W, Yan Q, Yang Y, Hong W, Yang G (2017) Preparation of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles by a microchannel technology. Eur J Pharm Sci 99:328–336. https://doi.org/10.1016/j.ejps.2017.01.00110.1016/j.ejps.2017.01.001 ↗

68. Xiong W, Peng L, Chen H, Li Q (2015) Surface modification of MPEG-b-PCL-based nanoparticles via oxidative self-polymerization of dopamine for malignant melanoma therapy. Int J Nanomed 10:2985–2996. https://doi.org/10.2147/ijn.S7960510.2147/ijn.S79605 ↗

69. Zhang H, Liu G, Zeng X, Wu Y, Yang C, Mei L, Wang Z, Huang L (2015) Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells. Int J Nanomed 10:2461–2473. https://doi.org/10.2147/ijn.S7898810.2147/ijn.S78988 ↗

70. Diwan R, Ravi PR, Agarwal SI, Aggarwal V (2021) Cilnidipine loaded poly (ε-caprolactone) nanoparticles for enhanced oral delivery: optimization using DoE, physical characterization, pharmacokinetic, and pharmacodynamic evaluation. Pharm Dev Technol 26(3):278–290. https://doi.org/10.1080/10837450.2020.186464310.1080/10837450.2020.1864643 ↗

71. Zhang D, Zou Z, Ren W, Qian H, Cheng Q, Ji L, Liu B, Liu Q (2018) Gambogic acid-loaded PEG-PCL nanoparticles act as an effective antitumor agent against gastric cancer. Pharm Dev Technol 23(1):33–40. https://doi.org/10.1080/10837450.2017.129506810.1080/10837450.2017.1295068 ↗

72. de Oliveira JER, Nascimento TL, Salomão MA, da Silva ACG, Valadares MC, Lima EM (2019) Increased nose-to-brain delivery of melatonin mediated by polycaprolactone nanoparticles for the treatment of glioblastoma. Pharm Res 36(9):131. https://doi.org/10.1007/s11095-019-2662-z10.1007/s11095-019-2662-z ↗

73. Noch EK, Ramakrishna R, Magge R (2018) Challenges in the treatment of glioblastoma: multisystem mechanisms of therapeutic resistance. World Neurosurg 116:505–517. https://doi.org/10.1016/j.wneu.2018.04.02210.1016/j.wneu.2018.04.022 ↗

74. Gu G, Xia H, Hu Q, Liu Z, Jiang M, Kang T, Miao D, Tu Y, Pang Z, Song Q, Yao L, Chen H, Gao X, Chen J (2013) PEG-co-PCL nanoparticles modified with MMP-2/9 activatable low molecular weight protamine for enhanced targeted glioblastoma therapy. Biomaterials 34(1):196–208. https://doi.org/10.1016/j.biomaterials.2012.09.04410.1016/j.biomaterials.2012.09.044 ↗

75. Qiu L, Hu B, Chen H, Li S, Hu Y, Zheng Y, Wu X (2015) Antifungal efficacy of itraconazole-loaded TPGS-b-(PCL-ran-PGA) nanoparticles. Int J Nanomed 10:1415–1423. https://doi.org/10.2147/ijn.S7161610.2147/ijn.S71616 ↗

76. Abriata JP, Eloy JO, Riul TB, Campos PM, Baruffi MD, Marchetti JM (2017) Poly-epsilon-caprolactone nanoparticles enhance ursolic acid in vivo efficacy against Trypanosoma cruzi infection. Mater Sci Eng C Mater Biol Appl 77:1196–1203. https://doi.org/10.1016/j.msec.2017.03.26610.1016/j.msec.2017.03.266 ↗

77. Khadka P, Ro J, Kim H, Kim I, Kim JT, Kim H, Cho JM, Yun G, Lee J (2014) Pharmaceutical particle technologies: an approach to improve drug solubility, dissolution and bioavailability. Asian J Pharm Sci 9(6):304–316. https://doi.org/10.1016/j.ajps.2014.05.00510.1016/j.ajps.2014.05.005 ↗

78. Feng R, Song Z, Zhai G (2012) Preparation and in vivo pharmacokinetics of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles. Int J Nanomed 7:4089–4098. https://doi.org/10.2147/ijn.S3360710.2147/ijn.S33607 ↗

79. Dubey N, Varshney R, Shukla J, Ganeshpurkar A, Hazari PP, Bandopadhaya GP, Mishra AK, Trivedi P (2012) Synthesis and evaluation of biodegradable PCL/PEG nanoparticles for neuroendocrine tumor targeted delivery of somatostatin analog. Drug Deliv 19(3):132–142. https://doi.org/10.3109/10717544.2012.65771810.3109/10717544.2012.657718 ↗

80. Prashant CK, Bhat M, Srivastava SK, Saxena A, Kumar M, Singh A, Samim M, Ahmad FJ, Dinda AK (2014) Fabrication of nanoadjuvant with poly-ε-caprolactone (Pcl) for developing a single-shot vaccine providing prolonged immunity. Int J Nanomed 9:937–950

81. Badri W, Miladi K, Robin S, Viennet C, Nazari QA, Agusti G, Fessi H, Elaissari A (2017) Polycaprolactone based nanoparticles loaded with indomethacin for anti-inflammatory therapy: from preparation to ex vivo study. Pharm Res 34(9):1773–1783. https://doi.org/10.1007/s11095-017-2166-710.1007/s11095-017-2166-7 ↗

82. Javaid S, Ahmad NM, Mahmood A, Nasir H, Iqbal M, Ahmad N, Irshad S (2021) Cefotaxime loaded polycaprolactone based polymeric nanoparticles with antifouling properties for in-vitro drug release applications. Polymers 13(13):2180. https://doi.org/10.3390/polym1313218010.3390/polym13132180 ↗

83. Zanetti M, Mazon LR, de Meneses AC, Silva LL, de Araújo PHH, Fiori MA, de Oliveira D (2019) Encapsulation of geranyl cinnamate in polycaprolactone nanoparticles. Mater Sci Eng C Mater Biol Appl 97:198–207. https://doi.org/10.1016/j.msec.2018.12.00510.1016/j.msec.2018.12.005 ↗

84. Rabha B, Bharadwaj KK, Baishya D, Sarkar T, Edinur HA, Pati S (2021) Synthesis and characterization of diosgenin encapsulated poly-ε-caprolactone-pluronic nanoparticles and its effect on brain cancer cells. Polymers 13(8):1322. https://doi.org/10.3390/polym1308132210.3390/polym13081322 ↗

85. Malikmammadov E, Tanir TE, Kiziltay A, Hasirci V, Hasirci N (2018) PCL and PCL-based materials in biomedical applications. J Biomater Sci Polym Ed 29(7–9):863–893. https://doi.org/10.1080/09205063.2017.139471110.1080/09205063.2017.1394711 ↗

86. da Silva RYP, de Menezes DLB, Oliveirad S, Converti A, de Lima Á A N, V (2023) Microparticles in the development and improvement of pharmaceutical formulations: an analysis of in vitro and in vivo studies. Int J Mol Sci 24(6):544110.3390/ijms24065441 ↗

87. Vilos C, Velasquez LA (2012) Therapeutic strategies based on polymeric microparticles. J Biomed Biotechnol 2012:672760. https://doi.org/10.1155/2012/67276010.1155/2012/672760 ↗

88. Brauner B, Schwarz P, Wirth M, Gabor F (2020) Micro vs. nano: PLGA particles loaded with trimethoprim for instillative treatment of urinary tract infections. Int J Pharm 579:119158. https://doi.org/10.1016/j.ijpharm.2020.11915810.1016/j.ijpharm.2020.119158 ↗

89. Lassalle V, Ferreira ML (2007) PLA nano- and microparticles for drug delivery: an overview of the methods of preparation. Macromol Biosci 7(6):767–783. https://doi.org/10.1002/mabi.20070002210.1002/mabi.200700022 ↗

90. Li M, Rouaud O, Poncelet D (2008) Microencapsulation by solvent evaporation: state of the art for process engineering approaches. Int J Pharm 363(1–2):26–39. https://doi.org/10.1016/j.ijpharm.2008.07.01810.1016/j.ijpharm.2008.07.018 ↗

91. Lee BK, Yun Y, Park K (2016) PLA micro- and nano-particles. Adv Drug Deliv Rev 107:176–191. https://doi.org/10.1016/j.addr.2016.05.02010.1016/j.addr.2016.05.020 ↗

92. Sadoun O, Rezgui F, G’Sell C (2018) Optimization of valsartan encapsulation in biodegradables polyesters using Box-Behnken design. Mater Sci Eng C Mater Biol Appl 90:189–197. https://doi.org/10.1016/j.msec.2018.04.04110.1016/j.msec.2018.04.041 ↗

93. Yang X, Yu B, Zhong Z, Guo BH, Huang Y (2018) Nevirapine-polycaprolactone crystalline inclusion complex as a potential long-acting injectable solid form. Int J Pharm 543(1–2):121–129. https://doi.org/10.1016/j.ijpharm.2018.03.04310.1016/j.ijpharm.2018.03.043 ↗

94. El Itawi H, Fadlallah S, Perré P, Allais F (2023) Microfluidics for polymer microparticles: opinion on sustainability and scalability. Sustain Chem 4:171–183. https://doi.org/10.3390/suschem402001310.3390/suschem4020013 ↗

95. Han JH, Kim CM, Kim T-H, Jin S, Kim GM (2022) Development of in situ microfluidic system for preparation of controlled porous microsphere for tissue engineering. Pharmaceutics 14(11):2345. https://doi.org/10.3390/pharmaceutics1411234510.3390/pharmaceutics14112345 ↗

96. Akolade JO, Balogun M, Swanepoel A, Ibrahim RB, Yusuf AA, Labuschagne P (2019) Microencapsulation of eucalyptol in polyethylene glycol and polycaprolactone using particles from gas-saturated solutions. RSC Adv 9(58):34039–34049. https://doi.org/10.1039/c9ra06419b10.1039/c9ra06419b ↗

97. Ferreira IS, Bettencourt AF, Gonçalves LM, Kasper S, Bétrisey B, Kikhney J, Moter A, Trampuz A, Almeida AJ (2015) Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms. Int J Nanomed 10:4351–4366. https://doi.org/10.2147/ijn.S8410810.2147/ijn.S84108 ↗

98. Fan YL, Hou HW, Tay HM, Guo WM, Berggren PO, Loo SCJ (2017) Preservation of anticancer and immunosuppressive properties of rapamycin achieved through controlled releasing particles. AAPS PharmSciTech 18(7):2648–2657. https://doi.org/10.1208/s12249-017-0745-x10.1208/s12249-017-0745-x ↗

99. Diab R, Hamoudeh M, Boyron O, Elaissari A, Fessi H (2010) Microencapsulation of cytarabine using poly(ethylene glycol)-poly(epsilon-caprolactone) diblock copolymers as surfactant agents. Drug Dev Ind Pharm 36(4):456–469. https://doi.org/10.3109/0363904090326198910.3109/03639040903261989 ↗

100. Somavarapu S, Pandit S, Gradassi G, Bandera M, Ravichandran E, Alpar OH (2005) Effect of vitamin E TPGS on immune response to nasally delivered diphtheria toxoid loaded poly(caprolactone) microparticles. Int J Pharm 298(2):344–347. https://doi.org/10.1016/j.ijpharm.2005.03.02910.1016/j.ijpharm.2005.03.029 ↗