hujpharm Hacettepe University Journal of the Faculty of Pharmacy 2458-8806 Hacettepe University 10.52794/hujpharm.1181365 Pharmacology and Pharmaceutical Sciences Eczacılık ve İlaç Bilimleri An Overview of In Vitro Release Test Methods Used In The Study of Nanoparticular Drug Delivery Systems Nanopartiküler İlaç Taşıyıcı Sistemlerinin İncelenmesinde Kullanılan İn Vitro Salım Testi Yöntemlerine Genel Bir Bakış https://orcid.org/0000-0002-4804-7495 Çobanoglu Ece MERSİN ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ, ECZACILIK TEKNOLOJİSİ BÖLÜMÜ, FARMASOTİK BİYOTEKNOLOJİ ANABİLİM DALI https://orcid.org/0000-0002-1467-3471 Şenel Sevda HACETTEPE ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ, ECZACILIK TEKNOLOJİSİ BÖLÜMÜ, FARMASÖTİK TEKNOLOJİ ANABİLİM DALI 03 01 2023 43 1 78 98 09 28 2022 01 28 2023 Copyright © 1981, Hacettepe University Journal of the Faculty of Pharmacy 1981 Hacettepe University Journal of the Faculty of Pharmacy

The in vitro release tests which examine the release properties of the drug from the dosage form provide the opportunity to investigate the in vitro availability of the drug product as well as to compare its equivalency to other products. In order to obtain accurate and reliable results from in vitro release tests, it is crucial to select the right release test method and suitable release conditions (such as temperature, release medium, pH, agitation/flow rate, etc.). Although there are compendial in vitro release test methods available for various dosage forms, up to date there are no tests described for nanoparticulate systems in any pharmacopeia. In this review, the methods (such as sampling and separation, membrane diffusion, continuous flow, etc.) applied to test the in vitro drug release from nanoparticulate systems will be reviewed. The recent applications of these methods in different particulate systems will be summarized and the advantages and limitations of these test methods will be discussed.

Bir ilacın dozaj şeklinden salım özelliklerinin incelenmesinde kullanılan in vitro salım testi sayesinde hem ilacın in vitro yararlanımı hakkında bilgi edinilmesi hem de diğer ürünlerle eşdeğerliğinin karşılaştırması mümkün olmaktadır. Doğru ve güvenilir sonuçlar elde edilmesi için uygun salım testi yönteminin ve uygun salım koşullarının (sıcaklık, salım ortamı, pH, karıştırma /akış hızı vb.) seçilmesi esastır. Farmakopelerde birçok dozaj şekli için in vitro salım testi yöntemleri ve koşulları tanımlanmış olmasına karşın hâlihazırda nanopartiküler ilaç taşıyıcı sistemler için bir test yöntemi farmakopelerde mevcut değildir. Bu derlemede, nanopartiküler sistemlerden ilaç salımının incelenmesinde kullanılan test yöntemleri (örnek alma ve ayırma, membran difüzyon, sürekli akış vb.) ve güncel uygulamalarından bahsedilecek ve birbirlerine olan üstünlükleri ve sakıncaları tartışılacaktır.

 nanopartiküler sistemler in vitro salım test yöntemleri örnek alma ve ayırma yöntemi membran difüzyon yöntemi sürekli akış yöntemi nanoparticulate systems in vitro release test methods sample and separate method membrane diffusion method continuous flow method FDA. (2011). Guidance for industry considering whether an FDA-regulated product involves the application of nanotechnology. Biotechnology Law Report, 30(5), 613–616. https://doi.org/10.1089/blr.2011.9814 Shen, J., Burgess, D. J. (2013). In vitro dissolution testing strategies for nanoparticulate drug delivery systems: recent developments and challenges. Drug Delivery And Translational Research, 3(5), 409–415. https://doi.org/10.1007/s13346-013-0129-z Chen, X., Han, W., Zhao, X., Tang, W., Wang, F. (2019). Epirubicin-loaded marine carragee nanoligosaccharide capped gold nanoparticle system for pH-triggered anticancer drug release. Scientific Reports, 9(1), 1–10. https://doi.org/10.1038/s41598-019-43106-9 Kammari, R., Das, N. G., Das, S. K. (2017). Nanoparticulate systems for therapeutic and diagnostic applications. In Emerging Nanotechnologies for Diagnostics, Drug Delivery and Medical Devices. https://doi.org/10.1016/B978-0-323-42978-8.00006-1 Cong, V. T., Houng, J. L., Kavallaris, M., Chen, X., Tilley, R. D., Gooding, J. J. (2022). How can we use the endocytosis pathways to design nanoparticle drug-delivery vehicles to target cancer cells over healthy cells?. Chemical Society reviews, 51(17), 7531–7559. https://doi.org/10.1039/d1cs00707f Patra, J. K., Das, G., Fraceto, L. F., Campos, E., Rodriguez-Torres, M., Acosta-Torres, L. S., Diaz-Torres, L. A., Grillo, R., Swamy, M. K., Sharma, S., Habtemariam, S., Shin, H. S. (2018). Nano based drug delivery systems: recent developments and future prospects. Journal of Nanobiotechnology, 16(1), 71. https://doi.org/10.1186/s12951-018-0392-8Hami 2021 Hami, Z. (2021). A brief review on advantages of nano-based drug delivery systems. Annals of Military and Health Sciences Research, 19(1), 1–6. https://doi.org/10.5812/amh.112274 Cao, Q., Li, X., Zhang, Q., Zhou, K., Yu, Y., He, Z., Xiang, Z., Qiang, Y., Qi, W. (2022). Big data analysis of manufacturing and preclinical studies of nanodrug-targeted delivery systems: a literature review. BioMed Research International, 2022, 1231446. https://doi.org/10.1155/2022/1231446 Ventola, C. L. (2017). Progress in nanomedicine: Approved and investigational nanodrugs. Pharmacy and Therapeutics (P and T), 42(12), 742–755. Teng, Z., Yu, M., Ding, Y., Zhang, H., Shen, Y., Jiang, M., Liu, P., Opoku-Damoah, Y., Webster, T. J., Zhou, J. (2018). Preparation and characterization of nimodipine-loaded nanostructured lipid systems for enhanced solubility and bioavailability. International Journal of Nanomedicine, 14, 119–133. https://doi.org/10.2147/IJN.S186899 Wang, Y., Khan, A., Liu, Y., Feng, J., Dai, L., Wang, G., Alam, N., Tong, L., Ni, Y. (2019). Chitosan oligosaccharide-based dual pH responsive nano-micelles for targeted delivery of hydrophobic drugs. Carbohydrate Polymers, 223, 115061. https://doi.org/10.1016/j.carbpol.2019.115061o Zhao, Y., Chen, G., Meng, Z., Gong, G., Zhao, W., Wang, K., Liu, T. (2019). A novel nanoparticle drug delivery system based on PEGylated hemoglobin for cancer therapy. Drug Delivery, 26(1), 717–723. https://doi.org/10.1080/10717544.2019.1639846 Gregoriadis, G., Perrie, Y. (2010). “Liposomes,” in Encylcopedia of Life Sciences (Chichester: John Wiley & Sons). doi: 10.1002/9780470015902.a0002656.pub2 Sahu, B. P., Das, M. K. (2014). Nanosuspension for enhancement of oral bioavailability of felodipine. Applied Nanoscience (Switzerland), 4(2), 189–197. https://doi.org/10.1007/s13204-012-0188-3 Pattni, B. S., Chupin, V. V., Torchilin, V. P. (2015). New developments in liposomal drug delivery. Chemical Reviews, 115(19), 10938–10966. https://doi.org/10.1021/acs.chemrev.5b00046 Kumar, M., Bishnoi, R. S., Shukla, A. K., Jain, C. P. (2019). Techniques for formulation of nanoemulsion drug delivery system: A review. Preventive Nutrition and Food Science, 24(3), 225–234. https://doi.org/10.3746/pnf.2019.24.3.225 Yahya, I., Atif, R., Ahmed, L., Eldeen, T. S., Omara, A., Eltayeb, M. (2019). Utilization of solid lipid nanoparticles loaded anticancer agents as drug delivery systems for controlled release. International Journal of Engineering Applied Sciences and Technology, 3(12), 7–16. https://doi.org/10.33564/ijeast.2019.v03i12.002 Balde, A., Hasan, A., Joshi, I., Nazeer, R. A. (2020). Preparation and optimization of chitosan nanoparticles from discarded squilla (Carinosquilla multicarinata) shells for the delivery of anti-inflammatory drug: Diclofenac. Journal of the Air & Waste Management Association (1995), 70(12), 1227–1235. https://doi.org/10.1080/10962247.2020.1727588 Sahu, T., Ratre, Y. K., Chauhan, S., Bhaskar, L. V. K. S., Nair, M. P., Verma, H. K. (2021). Nanotechnology based drug delivery system: Current strategies and emerging therapeutic potential for medical science. Journal of Drug Delivery Science and Technology, 63, 102487. https://doi.org/10.1016/j.jddst.2021.102487 D’Souza, S. (2014). A review of in vitro drug release test methods for nano-sized dosage forms . Advances in Pharmaceutics, 2014, 1–12. https://doi.org/10.1155/2014/304757 Gupta, R., Chen, Y., Xie, H. (2021). In vitro dissolution considerations associated with nano drug delivery systems. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 13(6), 1–34. https://doi.org/10.1002/wnan.1732 FDA. (1997). Guidance for Industry: dissolution testing of immediate release solid oral dosage forms; extended release solid oral dosage forms: development, evaluation and application of in vitro/in vivo correlations. Shah, V.P. (2005). The role of dissolution testing in the regulation of pharmaceuticals: The FDA perspective. Pharmaceutical Dissolution Testing 1st Edition, 16, eBook ISBN: 9780429163463 Wallace, S. J., Li, J., Nation, R. L., Boyd, B. J. (2012). Drug release from nanomedicines: Selection of appropriate encapsulation and release methodology. Drug Delivery And Translational Research, 2(4), 284–292. https://doi.org/10.1007/s13346-012-0064-4 USP 21: United States Pharmacopeia and the National Formulary. (1985). Rockville (MD): The United States Pharmacopeial Convention. USP 22: United States Pharmacopeia and the National Formulary. (USP 22 NF 18) (1990). Rockville (MD): The United States Pharmacopeial Convention. FIP. (1997). Guidelines for dissolution testing of solid oral products. https://www.fip.org/file/1557 Erişim Tarihi 19.09.2022 Dokoumetzidis, A., Macheras, P. (2006). A century of dissolution research: From Noyes and Whitney to the Biopharmaceutics Classification System. International Journal of Pharmaceutics, 321(1–2), 1–11. https://doi.org/10.1016/j.ijpharm.2006.07.011 Marroum, P. J. (2014). History and evolution of the dissolution test. Dissolution Technol, 21(3), 11-16. EMA/CHMP/CVMP/QWP (2017). Reflection paper on the dissolution specification for generic solid oral immediate release products with systemic action. .European Medicines Agency,(Ağustos),1-10. European pharmacopoeia. (2019). (10th ed.). Strasbourg: Council of Europe USP 43: United States Pharmacopeia and the National Formulary. (USP 43 NF 38) (2019). Rockville (MD): The United States Pharmacopeial Convention EMA/CHMP/QWP. (2014). Guideline on quality of oral modified release products. European Medicines Agency, 44(Mart), 1–16. https://doi.org/10.1016/S0022-3913(12)00047-9 Siewert, M., Dressman, J., Brown, C. K., Shah, V. P. (2003). FIP/AAPS guidelines for dissolution/in vitro release testing of novel/special dosage forms. Pharmazeutische Industrie, 65(2), 129–134. Brown, C. K., Friedel, H. D., Barker, A. R., Buhse, L. F., Keitel, S., Cecil, T. L., Kraemer, J., Morris, J. M., Reppas, C., Stickelmeyer, M. P., Yomota, C., Shah, V. P. (2011). FIP/AAPS joint workshop report: dissolution/in vitro release testing of novel/special dosage forms. Y., Wang, H., Li, C., Sun, B., Wang, Y., Wang, S., Gao, C. (2014). A novel three-dimensional large-pore mesoporous carbon matrix as a potential nanovehicle for the fast release of the poorly water-soluble drug, celecoxib. Pharmaceutical Research, 31(4), 1059–1070. https://doi.org/10.1007/s11095-013-1227-9 Serrano, D. R., Lalatsa, A., Dea-Ayuela, M. A., Bilbao-Ramos, P. E., Garrett, N. L., Moger, J., Guarro, J., Capilla, J., Ballesteros, M. P., Schätzlein, A. G., Bolás, F., Torrado, J. J., Uchegbu, I. F. (2015). Oral particle uptake and organ targeting drives the activity of amphotericin B nanoparticles. Molecular Pharmaceutics, 12(2), 420–431. https://doi.org/10.1021/mp500527x Tummala, S., Satish Kumar, M. N., Prakash, A. (2015). Formulation and characterization of 5-Fluorouracil enteric coated nanoparticles for sustained and localized release in treating colorectal cancer. Saudi Pharmaceutical Journal, 23(3), 308–314. https://doi.org/10.1016/j.jsps.2014.11.010 Gite, S., Chogale, M., Patravale, V. (2016). Development and validation of a discriminating dissolution method for atorvastatin delayed-release nanoparticles using a flow-through cell: A comparative study using USP apparatus 4 and 1. Dissolution Technologies, 23(2), 14–20. https://doi.org/10.14227/DT230216P14 Barzegar-Jalali, M., Alaei-Beirami, M., Javadzadeh, Y., Mohammadi, G., Hamidi, A., Andalib, S., Adibkia, K. (2012). Comparison of physicochemical characteristics and drug release of diclofenac sodium-eudragit® RS100 nanoparticles and solid dispersions. Powder Technology, 219, 211–216. https://doi.org/10.1016/j.powtec.2011.12.046 Varshosaz, J., Ghassami, E. (2015). Enhancement of dissolution rate of fenofibrate by spray drying technique: Comparison of eudragit E-100, solutol® HS15 and hydroxypropyl cellulose as carriers. Farmacia, 6(3), 433–445. Bohrey, S., Chourasiya, V., Pandey, A. (2016). Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study. Nano Convergence, 3(1), 3–9. https://doi.org/10.1186/s40580-016-0061-2 Putro, J. N., Ismadji, S., Gunarto, C., Soetaredjo, F. E., Ju, Y. H. (2020). A study of anionic, cationic, and nonionic surfactants modified starch nanoparticles for hydrophobic drug loading and release. Journal of Molecular Liquids, 298, 112034. https://doi.org/10.1016/j.molliq.2019.112034 Faisant, N., Akiki, J., Siepmann, F., Benoit, J. P., Siepmann, J. (2006). Effects of the type of release medium on drug release from PLGA-based microparticles: experiment and theory. International Journal of Pharmaceutics, 314(2), 189–197. https://doi.org/10.1016/j.ijpharm.2005.07.030 Mudie, D. M., Samiei, N., Marshall, D. J., Amidon, G. E., Bergström, C. (2020). Selection of in vivo predictive dissolution media using drug substance and physiological properties. The AAPS Journal, 22(2), 34. https://doi.org/10.1208/s12248-020-0417-8 Shameem, M., Lee, H., DeLuca, P. P. (1999). A short-term (accelerated release) approach to evaluate peptide release from PLGA depot formulations. AAPS PharmSci, 1(3), 1–6. https://doi.org/10.1208/ps010307 Tomic, I., Vidis-Millward, A., Mueller-Zsigmondy, M., Cardot, J. M. (2016). Setting accelerated dissolution test for PLGA microspheres containing peptide, investigation of critical parameters affecting drug release rate and mechanism. International Journal of Pharmaceutics, 505(1–2), 42–51. https://doi.org/10.1016/j.ijpharm.2016.03.048 Joshi, M., Pathak, S., Sharma, S., Patravale, V. (2008). Design and in vivo pharmacodynamic evaluation of nanostructured lipid carriers for parenteral delivery of artemether: Nanoject. International Journal of Pharmaceutics, 364(1), 119–126. https://doi.org/10.1016/j.ijpharm.2008.07.032 Bhardwaj, U., Burgess, D. J. (2010a). A novel USP apparatus 4 based release testing method for dispersed systems. International Journal of Pharmaceutics, 388(1–2), 287–294. https://doi.org/10.1016/j.ijpharm.2010.01.009 Abdel-Mottaleb, M. M. A., Lamprecht, A. (2011). Standardized in vitro drug release test for colloidal drug carriers using modified USP dissolution apparatus. Drug Development and Industrial Pharmacy, 37(2), 178–184. https://doi.org/10.3109/03639045.2010.502534 Gao, Y., Zuo, J., Bou-Chacra, N., Pinto, T. D. J. A., Clas, S. D., Walker, R. B., Löbenberg, R. (2013). In vitro release kinetics of antituberculosis drugs from nanoparticles assessed using a modified dissolution apparatus. BioMed Research International, 2013. https://doi.org/10.1155/2013/136590 Amatya, S., Park, E. J., Park, J. H. Park, Kim, J. S., Seol, E., Lee, H., Choi H, Y-H., Shin, Na, D. H. (2013). Drug release testing methods of polymeric particulate drug formulations. Journal of Pharmaceutical Investigation, 43(4), 259–266. https://doi.org/10.1007/s40005-013-0072-5 Yen, S. Y., Sung, K. C., Wang, J. J., Yoa-Pu Hu, O. (2001). Controlled release of nalbuphine propionate from biodegradable microspheres: In vitro and in vivo studies. International Journal of Pharmaceutics, 220(1–2), 91–99. https://doi.org/10.1016/S0378-5173(01)00649-4 Jeong, Y. I., Song, J. G., Kang, S. S., Ryu, H. H., Lee, Y. H., Choi, C., Shin, B. A., Kim, K. K., Ahn, K. Y., Jung, S. (2003). Preparation of poly(DL-lactide-co-glycolide) microspheres encapsulating all-trans retinoic acid. International Journal of Pharmaceutics, 259(1-2), 79–91. https://doi.org/10.1016/s0378-5173(03)00207-2 Prabha, S., Labhasetwar, V. (2004). Critical Determinants in PLGA/PLA Nanoparticle-Mediated Gene Expression. Pharmaceutical Research, 21(2), 354–364. https://doi.org/10.1023/B:PHAM.0000016250.56402.99 Danhier, F., Lecouturier, N., Vroman, B., Jérôme, C., Marchand-Brynaert, J., Feron, O., Préat, V. (2009). Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation. Journal of Controlled Release, 133(1), 11–17. https://doi.org/10.1016/j.jconrel.2008.09.086 Zhang, Y., Wang, H., Li, C., Sun, B., Wang, Y., Wang, S., Gao, C. (2014). A novel three-dimensional large-pore mesoporous carbon matrix as a potential nanovehicle for the fast release of the poorly water-soluble drug, celecoxib. Pharmaceutical Research, 31(4), 1059–1070. https://doi.org/10.1007/s11095-013-1227-9 Saim, M., Bashir, L., Naz, S., Ghayas, S., Bushra, R., Anwar, Z., Uddin, S.A., Korai, U. (2022). Development and characterization of cephradine proniosomes for oral controlled drug delivery. Indian Journal of Pharmaceutical Education and Research, 56, s67–s74. https://doi.org/10.5530/ijper.56.1s.44 Guo, W., Quan, P., Fang, L., Cun, D., Yang, M. (2015). Sustained release donepezil loaded PLGA microspheres for injection: Preparation, in vitro and in vivo study. Asian Journal of Pharmaceutical Sciences, 10(5), 405–414. https://doi.org/10.1016/j.ajps.2015.06.001 Prabha, S., Zhou, W. Z., Panyam, J., Labhasetwar, V. (2002). Size-dependency of nanoparticle-mediated gene transfection: Studies with fractionated nanoparticles. International Journal of Pharmaceutics, 244(1–2), 105–115. https://doi.org/10.1016/S0378-5173(02)00315-0 Sarhadi, S., Moosavian, S. A., Mashreghi, M., Rahiman, N., Golmohamadzadeh, S., Tafaghodi, M., Sadri, K., Chamani, J., Jaafari, M. R. (2022). B12-functionalized PEGylated liposomes for the oral delivery of insulin: In vitro and in vivo studies. Journal of Drug Delivery Science and Technology, 69. https://doi.org/10.1016/j.jddst.2022.103141 Yue, P. F., Lu, X. Y., Zhang, Z. Z., Yuan, H. L., Zhu, W. F., Zheng, Q., Yang, M. (2009). The study on the entrapment efficiency and in vitro release of puerarin submicron emulsion. AAPS PharmSciTech, 10(2), 376–383. https://doi.org/10.1208/s12249-009-9216-3 Heng, D., Cutler, D. J., Chan, H. K., Yun, J., Raper, J. A. (2008). What is a suitable dissolution method for drug nanoparticles? Pharmaceutical Research, 25(7), 1696–1701. https://doi.org/10.1007/s11095-008-9560-0 Fan, Y., Marioli, M., Zhang, K. (2021). Analytical characterization of liposomes and other lipid nanoparticles for drug delivery. Journal of Pharmaceutical and Biomedical Analysis, 192, 113642. https://doi.org/10.1016/j.jpba.2020.113642 Moghaddam, F. A., Ebrahimian, M., Oroojalian, F., Yazdian-Robati, R., Kalalinia, F., Tayebi, L., Hashemi, M. (2022). Effect of thymoquinone-loaded lipid–polymer nanoparticles as an oral delivery system on anticancer efficiency of doxorubicin. Journal of Nanostructure in Chemistry, 12(1), 33–44. https://doi.org/10.1007/s40097-021-00398-6 Liu, Y., Yang, G., Hui, Y., Ranaweera, S., Zhao, C. X. (2022). Microfluidic nanoparticles for drug delivery. Small, 2106580, 1–33. https://doi.org/10.1002/smll.202106580 Gulsun, T., Inal, M., Akdag, Y., Izat, N., Oner, L., Sahin, S. (2022). The development and characterization of electrospun gelatin nanofibers containing indomethacin and curcumin for accelerated wound healing. Journal of Drug Delivery Science and Technology, 6, 103000. https://doi.org/10.1016/j.jddst.2021.103000 Abedi, F., Davaran, S., Hekmati, M., Akbarzadeh, A., Baradaran, B., Moghaddam, S. V. (2021). An improved method in fabrication of smart dual-responsive nanogels for controlled release of doxorubicin and curcumin in HT-29 colon cancer cells. Journal of Nanobiotechnology, 19(1), 1–22. https://doi.org/10.1186/s12951-020-00764-6 Banarase, N. B., Kaur, C. D. (2022). Whole whey stabilized oleanolic acid nanosuspension: Formulation and evaluation study. Journal of Drug Delivery Science and Technology, 67, 103001. https://doi.org/10.1016/j.jddst.2021.103001 Mahkam, M., Hosseinzadeh, F., Galehassadi, M. (2012). Preparation of ionic liquid functionalized silica nanoparticles for oral drug delivery. Journal of Biomaterials and Nanobiotechnology, 03(03), 391–395. https://doi.org/10.4236/jbnb.2012.33038 Sarkhel, S., Ramsay, E., Kontturi, L. S., Peltoniemi, J., Urtti, A. (2014). High-through put in vitro drug release and pharmacokinetic simulation as a tool for drug delivery system development: Application to intravitreal ocular administration. International Journal of Pharmaceutics, 477(1–2), 469–475. https://doi.org/10.1016/j.ijpharm.2014.10.062 Zhang, Z., Feng, S. S. (2006). Nanoparticles of poly(lactide)/vitamin E TPGS copolymer for cancer chemotherapy: Synthesis, formulation, characterization and in vitro drug release. Biomaterials, 27(2), 262–270. https://doi.org/10.1016/j.biomaterials.2005.05.104 Beck-Broichsitter, M., Schweiger, C., Schmehl, T., Gessler, T., Seeger, W., Kissel, T. (2012). Characterization of novel spray-dried polymeric particles for controlled pulmonary drug delivery. Journal of Controlled Release, 158(2), 329–335. https://doi.org/10.1016/j.jconrel.2011.10.030 Ishihara, T., Kubota, T., Choi, T., Takahashi, M., Ayano, E., Kanazawa, H., Higaki, M. (2009). Polymeric nanoparticles encapsulating betamethasone phosphate with different release profiles and stealthiness. International Journal of Pharmaceutics, 375(1–2), 148–154. https://doi.org/10.1016/j.ijpharm.2009.04.001 Dong, Y., Feng S.S. (2006). Nanoparticles of poly(D,L-lactide)/methoxypoly(ethyleneglycol)-poly(D,L-lactide) blends for controlled release of paclitaxel. Journal of Biomedical Materials Research Part A, 79(4), 12–19. https://doi.org/10.1002/jbm.a Bisht, S., Feldmann, G., Koorstra, J. B., Mullendore, M., Alvarez, H., Karikari, C., Rudek, M. A., Lee, C. K., Maitra, A., & Maitra, A. (2008). In vivo characterization of a polymeric nanoparticle platform with potential oral drug delivery capabilities. Molecular Cancer Therapeutics, 7(12), 3878–3888. https://doi.org/10.1158/1535-7163.MCT-08-0476 Musumeci, T., Ventura, C. A., Giannone, I., Ruozi, B., Montenegro, L., Pignatello, R., Puglisi, G. (2006). PLA/PLGA nanoparticles for sustained release of docetaxel. International Journal of Pharmaceutics, 325(1–2), 172–179. https://doi.org/10.1016/j.ijpharm.2006.06.023 Morgen, M., Bloom, C., Beyerinck, R., Bello, A., Song, W., Wilkinson, K., Shamblin, S. (2012). Polymeric nanoparticles for increased oral bioavailability and rapid absorption using celecoxib as a model of a low-solubility, high-permeability drug. Pharmaceutical Research, 29(2), 427–440. https://doi.org/10.1007/s11095-011-0558-7 Avadi, M. R., Sadeghi, A. M. M., Mohammadpour, N., Abedin, S., Atyabi, F., Dinarvand, R., Rafiee-Tehrani, M. (2010). Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method. Nanomedicine: Nanotechnology, Biology, and Medicine, 6(1), 58–63. https://doi.org/10.1016/j.nano.2009.04.007 Gupta, H., Aqil, M., Khar, R. K., Ali, A., Bhatnagar, A., Mittal, G. (2010). Sparfloxacin-loaded PLGA nanoparticles for sustained ocular drug delivery. Nanomedicine: Nanotechnology, Biology, and Medicine, 6(2), 324–333. https://doi.org/10.1016/j.nano.2009.10.004 Panyam, J., Dali, M. M., Sahoo, S. K., Ma, W., Chakravarthi, S. S., Amidon, G. L., Levy, R. J., Labhasetwar, V. (2003). Polymer degradation and in vitro release of a model protein from poly(D,L-lactide-co-glycolide) nano- and microparticles. Journal of Controlled Release : Official Journal of The Controlled Release Society, 92(1-2), 173–187. https://doi.org/10.1016/s0168-3659(03)00328-6 Budhian, A., Siegel, S. J., Winey, K. I. (2008). Controlling the in vitro release profiles for a system of haloperidol-loaded PLGA nanoparticles. International Journal of Pharmaceutics, 346(1–2), 151–159. https://doi.org/10.1016/j.ijpharm.2007.06.011 Bhardwaj, U., Burgess, D. J. (2010b). Physicochemical properties of extruded and non-extruded liposomes containing the hydrophobic drug dexamethasone. International Journal of Pharmaceutics, 388(1–2), 181–189. https://doi.org/10.1016/j.ijpharm.2010.01.003 Khosa, A., Krishna, K. V., Dubey, S. K., Saha, R. N. (2020). Lipid nanocarriers for enhanced delivery of temozolomide to the brain. Methods In Molecular Biology (Clifton, N.J.), 2059, 285–298. https://doi.org/10.1007/978-1-4939-9798-5_15 Alajami, H. N., Fouad, E. A., Ashour, A. E., Kumar, A., Yassin, A. E. B. (2022). Celecoxib-loaded solid lipid nanoparticles for colon delivery: formulation optimization and in vitro assessment of anti-cancer activity. Pharmaceutics, 14(1). https://doi.org/10.3390/pharmaceutics14010131 Zafar, A., Yasir, M., Alruwaili, N. K., Imam, S. S., Alsaidan, O. A., Alshehri, S., Ghoneim, M. M., Alquraini, A., Rawaf, A., Ansari, M. J., Sara, U. (2022). Formulation of self-nanoemulsifying drug delivery system of cephalexin: physiochemical characterization and antibacterial evaluation. Polymers, 14(5), 1055. https://doi.org/10.3390/polym14051055 Moreno-Bautista, G., Tam, K. C. (2011). Evaluation of dialysis membrane process for quantifying the in vitro drug-release from colloidal drug carriers. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 389(1–3), 299–303. https://doi.org/10.1016/j.colsurfa.2011.07.032 Xu, X., Khan, M. A., Burgess, D. J. (2012). A two-stage reverse dialysis in vitro dissolution testing method for passive targeted liposomes. International Journal of Pharmaceutics, 426(1–2), 211–218. https://doi.org/10.1016/j.ijpharm.2012.01.030 D’Souza, S. S., DeLuca, P. P. (2006). Methods to assess in vitro drug release from injectable polymeric particulate systems. Pharmaceutical Research, 23(3), 460–474. https://doi.org/10.1007/s11095-005-9397-8 D’Souza, S., Amatya, S., Park, E. J., Park, J. H., Kim, J. S., Seol, E., … Wong, T. W. (2013). Drug release testing methods of polymeric particulate drug formulations. Organic Materials as Smart Nanocarriers for Drug Delivery, 47(1), 524–539. https://doi.org/10.1016/b978-0-12-813663-8.00003-8 Andhariya, J. V., Burgess, D. J. (2016). Recent advances in testing of microsphere drug delivery systems. Expert Opinion on Drug Delivery, 13(4), 593–608. https://doi.org/10.1517/17425247.2016.1134484 Kim, Y., Park, E. J., Kim, T. W., Na, D. H. (2021). Recent progress in drug release testing methods of biopolymeric particulate system. Pharmaceutics, 13(8), 1–23. https://doi.org/10.3390/pharmaceutics13081313 Bhagav, P., Upadhyay, H., Chandran, S. (2011). Brimonidine tartrate-eudragit long-acting nanoparticles: formulation, optimization, in vitro and in vivo evaluation. AAPS PharmSciTech, 12(4), 1087–1101. https://doi.org/10.1208/s12249-011-9675-1 Abdel-Mottaleb, M. M. A., Neumann, D., Lamprecht, A. (2010). In vitro drug release mechanism from lipid nanocapsules (LNC). International Journal of Pharmaceutics, 390(2), 208–213. https://doi.org/10.1016/j.ijpharm.2010.02.001 Ge, Z., Ma, R., Xu, G., Chen, Z., Zhang, D., Wang, Q., Hei, L., Ma, W. (2018). Development and in vitro release of isoniazid and rifampicin-loaded bovine serum albumin nanoparticles. Medical Science Monitor : International Medical Journal of Experimental And Clinical Research, 24, 473–478. https://doi.org/10.12659/msm.905581 Küp, F. Ö., Çoşkunçay, S., Duman, F. (2020). Biosynthesis of silver nanoparticles using leaf extract of Aesculus hippocastanum (horse chestnut): Evaluation of their antibacterial, antioxidant and drug release system activities. Materials Science and Engineering C, 107, 110207. https://doi.org/10.1016/j.msec.2019.110207 Patil, P., Killedar, S., More, H., Vambhurkar, G. (2022). Development and characterization of 5-fluorouracil solid lipid nanoparticles for treatment of colorectal cancer. Journal of Pharmaceutical Innovation, (0123456789). https://doi.org/10.1007/s12247-021-09605-x Etman, S. M., Abdallah, O. Y., Mehanna, R. A., Elnaggar, Y. (2020). Lactoferrin/Hyaluronic acid double-coated lignosulfonate nanoparticles of quinacrine as a controlled release biodegradable nanomedicine targeting pancreatic cancer. International Journal of Pharmaceutics, 578, 119097. https://doi.org/10.1016/j.ijpharm.2020.119097 Godara, S., Lather, V., Kirthanashri, S. V., Awasthi, R., Pandita, D. (2020). Lipid-PLGA hybrid nanoparticles of paclitaxel: Preparation, characterization, in vitro and in vivo evaluation. Materials Science & Engineering. C, Materials For Biological Applications, 109, 110576. https://doi.org/10.1016/j.msec.2019.110576 Najafzadeh, M., Bakhshandeh, H., Zamani, Z., Movahedi, M., Atyabi, S. M. (2022). Preparation, characterization, and evaluation of eosin B–loaded nano-liposomes for growth inhibition of Plasmodium falciparum. Parasitology Research, 121(1), 383–393. https://doi.org/10.1007/s00436-021-07395-2 Sambamoorthy, U., Manjappa, A. S., Eswara, B. R. M., Sanapala, A. K., Nagadeepthi, N. (2022). Vitamin E oil ıncorporated liposomal melphalan and simvastatin: approach to obtain ımproved physicochemical characteristics of hydrolysable melphalan and anticancer activity in combination with simvastatin against multiple myeloma. AAPS PharmSciTech, 23(1). https://doi.org/10.1208/s12249-021-02177-6 Londhe, V. Y., Sharma, S. (2022). Formulation, characterization, optimization and in-vivo evaluation of methazolamide liposomal in-situ gel for treating glaucoma. Journal of Drug Delivery Science and Technology, 67, 102951. https://doi.org/10.1016/j.jddst.2021.102951 Đoković, J., Konkel, M., Mitrović, J., Savic, S. M., Cekić, N., Savić, S. D. (2019). PEG-ylated parenteral nanoemulsions as prospective carriers for enhanced brain delivery with diazepam as a model drug – physicochemical characterization. Symposium on Pharmaceutical Engineering Research SPhERe. https://doi.org/10.24355/dbbs.084-202001221435-0 Suresh, P., Salem-Bekhit, M. M., Veedu, H. P., Alshehri, S., Nair, S. C., Bukhari, S. I., Viswanad, V., Taha, E. I., Sahu, R. K., Ghoneim, M. M., Elbagory, I. (2022). Development of a novel methotrexate-loaded nanoemulsion for rheumatoid arthritis treatment with site-specific targeting subcutaneous delivery. Nanomaterials (Basel, Switzerland), 12(8), 1299. https://doi.org/10.3390/nano12081299 Gorle, A., Ahire, K., Shende, R. (2022). Design, Development aa. Journal of Drug Delivery and Therapeutics, 12(2), 24–32. https://doi.org/10.22270/jddt.v12i2.5245 Farooq, M.A., Xu, L., Aquib M., Ahsan, A., Mirza Baig, M.F.A., Wang, B.(2019). Denatured food protein-coated nanosuspension: A promising approach for anticancer delivery of hydrophobic drug. Journal of Molecular Liquids. Sezgin-Bayindir, Z., Antep, M. N., Yuksel, N. (2014). Development and characterization of mixed niosomes for oral delivery using candesartan cilexetil as a model poorly water-soluble drug. AAPS PharmSciTech, 16(1), 108–117. https://doi.org/10.1208/s12249-014-0213-9 Zhang, Y., Wang, C., Huang, Y., Yan, H., Liu, K. (2015). Core-crosslinked polymeric micelles with high doxorubicin loading capacity and intracellular pH- and redox-triggered payload release. European Polymer Journal, 68, 104–114. https://doi.org/10.1016/j.eurpolymj.2015.04.033 Al-Nemrawi, N. K., Altawabeyeh, R. M., Darweesh, R. S. (2022). Preparation and characterization of docetaxel-plga nanoparticles coated with folic acid-chitosan conjugate for cancer treatment. Journal of Pharmaceutical Sciences, 111(2), 485–494. https://doi.org/10.1016/j.xphs.2021.10.034 Rabanel, J. M., Faivre, J., Paka, G. D., Ramassamy, C., Hildgen, P., Banquy, X. (2015). Effect of polymer architecture on curcumin encapsulation and release from PEGylated polymer nanoparticles: Toward a drug delivery nano-platform to the CNS. European Journal of Pharmaceutics and Biopharmaceutics, 96, 409–420. https://doi.org/10.1016/j.ejpb.2015.09.004 Bohrey, S., Chourasiya, V., Pandey, A. (2016). Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study. Nano Convergence, 3(1), 3–9. https://doi.org/10.1186/s40580-016-0061-2 Muntimadugu, E., Dhommati, R., Jain, A., Challa, V. G. S., Shaheen, M., Khan, W. (2016). Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer’s disease. European Journal of Pharmaceutical Sciences, 92, 224–234. https://doi.org/10.1016/j.ejps.2016.05.012 Öztürk, A. A., Yenilmez, E., Yazan, Y. (2019). Dexketoprofen trometamol-loaded Eudragit® RL 100 nanoparticle formulation, characterization and release kinetics. Acta Pharmaceutica Sciencia, 57(1), 69–84. https://doi.org/10.23893/1307-2080.APS.05705 Esfandyari-Manesh, M., Abdi, M., Talasaz, A. H., Ebrahimi, S. M., Atyabi, F., Dinarvand, R. (2020). S2P peptide-conjugated PLGA-Maleimide-PEG nanoparticles containing Imatinib for targeting drug delivery to atherosclerotic plaques. DARU, Journal of Pharmaceutical Sciences. https://doi.org/10.1007/s40199-019-00324-w Fan, W., Xu, Y., Li, Z., Li, Q. (2019). Folic acid-modified β-cyclodextrin nanoparticles as drug delivery to load DOX for liver cancer therapeutics. Soft Materials, 17(4), 437–447. https://doi.org/10.1080/1539445X.2019.1624265 Afshar, M., Dini, G., Vaezifar, S., Mehdikhani, M., Movahedi, B. (2020). Preparation and characterization of sodium alginate/polyvinylalcohol hydrogel containing drug-loaded chitosan nanoparticles as a drug delivery system. Journal of Drug Delivery Science and Technology, 56, 101530. https://doi.org/10.1016/j.jddst.2020.101530 Yu, A., Shi, H., Liu, H., Bao, Z., Dai, M., Lin, D., Lin, D., Xu, X., Li, X., Wang, Y. (2020). Mucoadhesive dexamethasone-glycol chitosan nanoparticles for ophthalmic drug delivery. International Journal of Pharmaceutics, 575, 118943. https://doi.org/10.1016/j.ijpharm.2019.118943 Wang,Y., Yang, X., Yang, J., Wang, Y., Chen, R., Wu, J., Liu, Y., Zhang, N. (2011). Self-assembled nanoparticles of methotrexate conjugated O-carboxymethyl chitosan: Preparation, characterization and drug release behavior in vitro. Carbohydrate Polymers, 86(4), 1665–1670. https://doi.org/10.1016/j.carbpol.2011.06.080 Xiong, X. Y., Tam, K. C., Gan, L. H. (2005). Release kinetics of hydrophobic and hydrophilic model drugs from pluronic F127/poly(lactic acid) nanoparticles. Journal of Controlled Release, 103(1), 73–82. https://doi.org/10.1016/j.jconrel.2004.11.018 Ge, H., Hu, Y., Jiang, X., Cheng, D., Yuan, Y., Bi, H., Yang, C. (2002). Preparation, characterization, and drug release behaviors of drug nimodipine-loaded poly(ε-caprolactone)-poly(ethylene oxide)-poly(ε-caprolactone) amphiphilic triblock copolymer micelles. Journal of Pharmaceutical Sciences, 91(6), 1463–1473. https://doi.org/10.1002/jps.10143 Avgoustakis, K., Beletsi, A., Panagi, Z., Klepetsanis, P., Karydas, A. G., Ithakissios, D. S. (2002). PLGA-mPEG nanoparticles of cisplatin: In vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties. Journal of Controlled Release, 79(1–3), 123–135. https://doi.org/10.1016/S0168-3659(01)00530-2 Hu, Y., Jiang, X., Ding, Y., Zhang, L., Yang, C., Zhang, J., Chen, J., Yang, Y. (2003). Preparation and drug release behaviors of nimodipine-loaded poly(caprolactone)-poly(ethylene oxide)-polylactide amphiphilic copolymer nanoparticles. Biomaterials, 24(13), 2395–2404. https://doi.org/10.1016/s0142-9612(03)00021-8 Peracchia, M. T., Gref, R., Minamitake, Y., Domb, A., Lotan, N., Langer, R. (1997). PEG-coated nanospheres from amphiphilic diblock and multiblock copolymers: Investigation of their drug encapsulation and release characteristics. Journal of Controlled Release, 46(3), 223–231. https://doi.org/10.1016/S0168-3659(96)01597-0 Liu, M., Li, H., Luo, G., Liu, Q., Wang, Y. (2008). Pharmacokinetics and biodistribution of surface modification polymeric nanoparticles. Archives of Pharmacal Research, 31(4), 547–554. https://doi.org/10.1007/s12272-001-1191-8 Liu, M., Dong, J., Yang, Y., Yang, X., Xu, H. (2005). Characterization and release of triptolide-loaded poly (D, L-lactic acid) nanoparticles. European Polymer Journal, 41(2), 375–382. https://doi.org/10.1016/j.eurpolymj.2004.09.015 Mittal, G., Sahana, D. K., Bhardwaj, V., Ravi Kumar, M. N. V. (2007). Estradiol loaded PLGA nanoparticles for oral administration: Effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo. Journal of Controlled Release, 119(1), 77–85. https://doi.org/10.1016/j.jconrel.2007.01.016 Jeon, H. J., Jeong, Y. Il, Jang, M. K., Park, Y. H., Nah, J. W. (2000). Effect of solvent on the preparation of surfactant-free poly(DL-lactide-co-glycolide) nanoparticles and norfloxacin release characteristics. International Journal of Pharmaceutics, 207(1–2), 99–108. https://doi.org/10.1016/S0378-5173(00)00537-8 Sant, S., Nadeau, V., &Hildgen, P. (2005). Effect of porosity on the release kinetics of propafenone-loaded PEG-g-PLA nanoparticles. Journal of Controlled Release, 107(2), 203–214. https://doi.org/10.1016/j.jconrel.2005.02.017 Zaghloul, N., Hoffy, N. M. E., Mahmoud, A. A., Elkasabgy, N. A. (2022). Cyclodextrin stabilized freeze-dried silica/chitosan nanoparticles for improved terconazole ocular bioavailability. Pharmaceutics, 14(3). https://doi.org/10.3390/pharmaceutics14030470 Iyer, S. S., Barr, W. H., Karnes, H. T. (2006). Profiling in vitro drug release from subcutaneous implants: A review of current status and potential implications on drug product development. Biopharmaceutics and Drug Disposition. https://doi.org/10.1002/bdd.493 Fotaki, N. (2011). Flow-through cell apparatus (USP apparatus 4):Operation and features. Dissolution Technologies, 18, 46-49 Wagenaar, B. W., Müller, B. W. (1994). Piroxicam release from spray-dried biodegradable microspheres. Biomaterials, 15(1), 49–54. https://doi.org/10.1016/0142-9612(94)90196-1 Wang, J., Wang, B. M., Schwendeman, S. P. (2002). Characterization of the initial burst release of a model peptide from poly(D,L-lactide-co-glycolide) microspheres. Journal of Controlled Release, 82(2–3), 289–307. https://doi.org/10.1016/S0168-3659(02)00137-2 Rawat, A., Bhardwaj, U., Burgess, D. J. (2012). Comparison of in vitro-in vivo release of Risperdal® Consta® microspheres. International Journal of Pharmaceutics, 434(1–2), 115–121. https://doi.org/10.1016/j.ijpharm.2012.05.006 Tang, J., Srinivasan, S., Yuan, W., Ming, R., Liu, Y., Dai, Z., Noble, C. O., Hayes, M. E., Zheng, N., Jiang, W., Szoka, F. C., Schwendeman, A. (2019). Development of a flow-through USP 4 apparatus drug release assay for the evaluation of amphotericin B liposome. European journal of pharmaceutics and biopharmaceutics, 134, 107–116. https://doi.org/10.1016/j.ejpb.2018.11.010 Morais, J. M., Burgess, D. J. (2014). In vitro release testing methods for vitamin e nanoemulsions. International Journal of Pharmaceutics, 475(1), 393–400. https://doi.org/10.1016/j.ijpharm.2014.08.063 Wallenwein, C. M., Nova, M. V., Janas, C., Jablonka, L., Gao, G. F., Thurn, M., Albrecht, V., Wiehe, A., & Wacker, M. G. (2019). A dialysis-based in vitro drug release assay to study dynamics of the drug-protein transfer of temoporfin liposomes. European Journal of Pharmaceutics and Biopharmaceutics, 143, 44–50. https://doi.org/10.1016/j.ejpb.2019.08.010 Nothnagel, L., Wacker, M. G. (2018). How to measure release from nanosized carriers? European Journal of Pharmaceutical Sciences, 120, 199–211. https://doi.org/10.1016/j.ejps.2018.05.004 Manna, S., Wu, Y., Wang, Y., Koo, B., Chen, L., Petrochenko, P., Dong, Y., Choi, S., Kozak, D., Oktem, B., Xu, X., Zheng, J. (2019). Probing the mechanism of bupivacaine drug release from multivesicular liposomes. Journal of Controlled Release : Official Journal of The Controlled Release Society, 294, 279–287. https://doi.org/10.1016/j.jconrel.2018.12.029