摘要
台灣50歲以上人口的數量已從2001年的490萬增加到2013年的750萬。骨骼疾病是影響老年人的主要問題，這些老年人的骨骼可能已經存在嚴重的脆弱性和功能性衰弱。骨質脆弱性即主要定義為骨質疏鬆症，為與年齡相關的骨折有關。同時，骨折可能以各種方式發生，不僅是由於骨質疏鬆所致，還涵蓋一些問題，其中包括交通事故、跌倒、運動損傷或施加在骨骼上過大的力。根據軟組織是否參與，它分為閉鎖性骨折和開放性骨折。在這種情況下，開放性骨折需要特殊處理，因為骨頭的一部分會穿透皮膚並造成傷口。來自灰塵、污垢和其他污染物的細菌會入侵傷口並引起骨感染(骨髓炎)。抗生素可用於治療骨髓炎，選擇合適的藥物載體可以達到足夠的治療效果，並防止感染的風險。由於具有生物相容性，生物降解性和生物活性等特性，生醫玻璃(BG)是用於骨植入物和藥物載體的潛在生醫材料。
在這項研究中，造粒技術被應用於製備BG微球與PEG和澱粉的混合，作為造孔劑，使用不同的濃度(0、5、10和20 wt％)。透過噴霧乾燥法(SD)合成BG微球。再將抗生素裝入內部以延長藥物的釋放時間後，使用殼聚醣包裹BG微球。利用四環黴素(Tc)用作體外藥物釋放測試的治療性抗生素。通過X光繞射儀(XRD)、掃描式電子顯微鏡(SEM)、氮氣吸/脫附曲線分析儀(BET)、傅立葉轉換紅外線光譜儀(FTIR)、和螢光微量盤分光光譜儀(體外藥物釋放測試)。
結果顯示，甲殼素可以延長藥物的釋放時間。在pH 7.4和pH 5的PBS溶液中，甲殼素包覆10 wt％聚乙二醇(PEG)處理的BG微球具有最高的累積四環黴素釋放百分比，在pH 7.4下，直到240小時仍存在藥物釋放的趨勢；而在pH 5下，從144h到240h持續釋放。在pH 7.4和pH 5的PBS溶液中，甲殼素包覆20 wt％澱粉處理的BG微球具有最高的累積四環黴素釋放百分比，在pH 7.4時，直到240 h都有藥物釋放的趨勢；而在pH 5時，則是從144 h到240 h為持續釋放。
關鍵字：生醫玻璃(BG)、微球、甲殼素、噴霧乾燥、藥物釋放

Abstract
The number of adults over 50 years in Taiwan has increased from 4.9 million in 2001 to 7.5 million in 2013. The majority of the problem is about the bone disease that affects older people primarily, who may already have significant problems with fragility and decreased functional ability. The bone fragility mainly defined as osteoporosis, which associated with age-related fractures. Meanwhile, bone fractures can occur in various ways, not only because of osteoporosis but also some issues, including car accidents, falls, sports injuries or other excessive force applied to the bone. Due to the soft-tissue involvement, it is divided into closed and open fractures. In this case, the open fracture requires special treatment because a fragment of the bone breaking through the skin and causes a wound. The bacteria from dust, dirt, and other contaminants can invade the wound and cause bone infection (osteomyelitis). Antibiotics can be used as the treatment of osteomyelitis. Choosing a suitable drug carrier can achieve an adequate therapeutic effect and prevent the risk of infection. Bioactive glass (BG) is a potential biomaterial for the bone-implant and drug carrier due to properties such as biocompatibility, biodegradability, and bioactivity.
In this study, granulation technology was used to prepare the BG microspheres mix with PEG and starch as pore-forming agents using different concentrations (0, 5, 10, and 20 wt%). BG microspheres were synthesized by spray drying (SD). The chitosan was used to coat the BG microspheres after load the antibiotic inside to prolong the time release of the drug. Tetracycline (TC) used as a therapeutic antibiotic for the in vitro drug release test. Samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), nitrogen adsorption/desorption isotherm (BET), transform infrared spectroscopy (FTIR), and a fluorescence microplate reader (in vitro drug release test).
The results show that chitosan can prolong the time release of the drug. The chitosan encapsulated 10 wt% PEG-treated BG microspheres in pH 7.4 and pH 5 of PBS solution has the highest cumulative tetracycline release percentage. However, in pH 7.4, there was still a trend of drug release until 240 h, while in pH 5 sustained release from 144 h until 240 h. The chitosan encapsulated 20 wt% starch-treated BG microspheres in pH 7.4 and pH 5 of PBS solution has the highest cumulative tetracycline release percentage. Nonetheless, in pH 7.4, there was a trend of drug release until 240 h, while in pH 5 sustained release from 144 h until 240 h.
Keywords: Bioactive glass (BG), microsphere, chitosan, spray drying, drug release.

References
[1] W.H. Organization, WHO scientific group on the assessment of osteoporosis at primary health care level, Summary meeting report, 2004, pp. 5-7.
[2] U. Nations, Department of economic and social affairs, population division,‘World population ageing 2013ʹ (ST/ESA/SER. A/348), United Nations New York, NY, 2013.
[3] F.-P. Chen, T.-S. Huang, T.-S. Fu, C.-C. Sun, A.-S. Chao, T.-L. Tsai, Secular trends in incidence of osteoporosis in Taiwan: A nationwide population-based study, biomedical journal, 41 (2018) 314-320.
[4] O.o.t.S. General, Bone health and osteoporosis: a report of the Surgeon General, (2004).
[5] S.M. Cadarette, S.B. Jaglal, T.M. Murray, W.J. McIsaac, L. Joseph, J.P. Brown, Evaluation of decision rules for referring women for bone densitometry by dual-energy x-ray absorptiometry, Jama, 286 (2001) 57-63.
[6] S. Parmet, C. Lynm, R.M. Glass, Bone Fractures, JAMA, 291 (2004) 2160-2160.
[7] A. Katherine, Official CPC Certification Study Guide, American Medical Association, (2013) 108.
[8] S. Chihara, J. Segreti, Osteomyelitis, Disease-a-month: DM, 56 (2010) 5-31.
[9] T. Alonge, S. Salawu, A. Adebisi, A. Fashina, The choice of antibiotic in open fractures in a teaching hospital in a developing country, International journal of clinical practice, 56 (2002) 353-356.
[10] S. Aytaç, M. Schnetzke, B. Swartman, P. Herrmann, C. Woelfl, V. Heppert, P.A. Gruetzner, T. Guehring, Posttraumatic and postoperative osteomyelitis: surgical revision strategy with persisting fistula, Archives of orthopaedic and trauma surgery, 134 (2014) 159-165.
[11] H. Qu, H. Fu, Z. Han, Y. Sun, Biomaterials for bone tissue engineering scaffolds: a review, RSC advances, 9 (2019) 26252-26262.
[12] Z. Sheikh, N. Hamdan, Y. Ikeda, M. Grynpas, B. Ganss, M. Glogauer, Natural graft tissues and synthetic biomaterials for periodontal and alveolar bone reconstructive applications: a review, Biomaterials research, 21 (2017) 9.
[13] W. Thein-Han, R. Misra, Biomimetic chitosan–nanohydroxyapatite composite scaffolds for bone tissue engineering, Acta biomaterialia, 5 (2009) 1182-1197.
[14] T.P. Sculco, The economic impact of infected joint arthroplasty, Orthopedics, 18 (1995) 871-873.
[15] M. Navarro, A. Michiardi, O. Castano, J. Planell, Biomaterials in orthopaedics, Journal of the royal society interface, 5 (2008) 1137-1158.
[16] B.D. Ratner, A.S. Hoffman, F.J. Schoen, J.E. Lemons, Biomaterials science: an introduction to materials in medicine, Elsevier2004.
[17] E. Wintermantel, S.-W. Ha, Medizintechnik mit biokompatiblen Werkstoffen und Verfahren, Springer2002.
[18] D. Williams, Consensus and definitions in biomaterials, Advances in biomaterials, 8 (1980) 11-16.
[19] S. Bauer, P. Schmuki, K. Von Der Mark, J. Park, Engineering biocompatible implant surfaces: Part I: Materials and surfaces, Progress in Materials Science, 58 (2013) 261-326.
[20] S. Devgan, S.S. Sidhu, Evolution of surface modification trends in bone related biomaterials: A review, Materials Chemistry and Physics, 233 (2019) 68-78.
[21] D.F. Williams, There is no such thing as a biocompatible material, Biomaterials, 35 (2014) 10009-10014.
[22] B.D. Ratner, A perspective on titanium biocompatibility, Titanium in medicine, Springer2001, pp. 1-12.
[23] R. Lanza, R. Langer, J.P. Vacanti, Principles of tissue engineering, Academic press2011.
[24] M.J. Lysaght, J. Reyes, The growth of tissue engineering, Tissue engineering, 7 (2001) 485-493.
[25] J.P. Vacanti, R. Langer, Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation, The lancet, 354 (1999) S32-S34.
[26] J.G. Betts, P. DeSaix, E. Johnson, J.E. Johnson, O. Korol, D.H. Kruse, B. Poe, J.A. Wise, K.A. Young, Anatomy and physiology, (2014).
[27] M.J. Bosse, E.J. MacKenzie, J.F. Kellam, A.R. Burgess, L.X. Webb, M.F. Swiontkowski, R.W. Sanders, A.L. Jones, M.P. McAndrew, B.M. Patterson, An analysis of outcomes of reconstruction or amputation after leg-threatening injuries, New England Journal of Medicine, 347 (2002) 1924-1931.
[28] J.W. Busse, C.L. Jacobs, M.F. Swiontkowski, M.J. Bosse, M. Bhandari, E.-B.O.T.W. Group, Complex limb salvage or early amputation for severe lower-limb injury: a meta-analysis of observational studies, Journal of orthopaedic trauma, 21 (2007) 70-76.
[29] P. Warnke, I. Springer, J. Wiltfang, Y. Acil, H. Eufinger, M. Wehmöller, P. Russo, H. Bolte, E. Sherry, E. Behrens, Growth and transplantation of a custom vascularised bone graft in a man, The Lancet, 364 (2004) 766-770.
[30] G. Lyritis, H. Frost, W. Jee, M. Koutsilieris, C. Mitsiades, P. Lembessis, A. Sourla, D. Kalu, J. Banu, L. Wang, The history of the walls of the Acropolis of Athens and the natural history of secondary fracture healing process, J Musculoskelet Neuronal Interact, 1 (2000) 1-3.
[31] A. Diwan, K.R. Eberlin, R.M. Smith, The principles and practice of open fracture care, 2018, Chinese Journal of Traumatology, 21 (2018) 187-192.
[32] https://difference.guru/difference-between-an-open-and-a-closed-fracture/.
[33] G.G. Ram, V.A. Chander, S. Rajappa, Amputees have better quality of life than who had limb salvaged in grade iii B and grade iii C crush injury, Indian J Orthop Surg, 1 (2015) 146-148.
[34] L.X. Webb, M.J. Bosse, R.C. Castillo, E.J. MacKenzie, L.S. Group, Analysis of surgeon-controlled variables in the treatment of limb-threatening type-III open tibial diaphyseal fractures, JBJS, 89 (2007) 923-928.
[35] J. Osborn, Biomaterials and their application to implantation, Schweizerische Monatsschrift fur Zahnheilkunde= Revue mensuelle suisse d'odonto-stomatologie, 89 (1979) 1138-1139.
[36] M. Ribeiro, F.J. Monteiro, M.P. Ferraz, Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial-material interactions, Biomatter, 2 (2012) 176-194.
[37] K. Duan, R. Wang, Surface modifications of bone implants through wet chemistry, Journal of materials chemistry, 16 (2006) 2309-2321.
[38] B. Ercan, K.M. Kummer, K.M. Tarquinio, T.J. Webster, Decreased Staphylococcus aureus biofilm growth on anodized nanotubular titanium and the effect of electrical stimulation, Acta biomaterialia, 7 (2011) 3003-3012.
[39] M. Zilberman, J.J. Elsner, Antibiotic-eluting medical devices for various applications, Journal of controlled release, 130 (2008) 202-215.
[40] A. Gristina, P. Naylor, Q. Myrvik, Infections from biomaterials and implants: a race for the surface, Medical progress through technology, 14 (1988) 205-224.
[41] D. Davies, Understanding biofilm resistance to antibacterial agents, Nature reviews Drug discovery, 2 (2003) 114.
[42] D. Campoccia, L. Montanaro, C.R. Arciola, The significance of infection related to orthopedic devices and issues of antibiotic resistance, Biomaterials, 27 (2006) 2331-2339.
[43] S.J. Kalita, S. Verma, Nanocrystalline hydroxyapatite bioceramic using microwave radiation: Synthesis and characterization, Materials Science and Engineering: C, 30 (2010) 295-303.
[44] J.A. Wright, S.P. Nair, Interaction of staphylococci with bone, International journal of medical microbiology, 300 (2010) 193-204.
[45] R. Brady, J. Leid, J. Costerton, M. Shirtliff, Osteomyelitis: clinical overview and mechanisms of infection persistence, Clinical Microbiology Newsletter, 28 (2006) 65-72.
[46] S. Sawan, G. Manivannan, Antimicrobial/Anti-Infective Materials, Pennsylvania: Technomic Publishers, (2000).
[47] E.S. Darley, A.P. MacGowan, Antibiotic treatment of gram-positive bone and joint infections, Journal of antimicrobial chemotherapy, 53 (2004) 928-935.
[48] L. Lazzarini, J.T. Mader, J.H. Calhoun, Osteomyelitis in long bones, JBJS, 86 (2004) 2305-2318.
[49] W. Gillespie, Epidemiology in bone and joint infection, Infectious disease clinics of North America, 4 (1990) 361-376.
[50] G.H. Walenkamp, How I do it: Chronic osteomyelitis, Acta Orthopaedica Scandinavica, 68 (1997) 497-506.
[51] A. Trampuz, W. Zimmerli, Diagnosis and treatment of infections associated with fracture-fixation devices, Injury, 37 (2006) S59-S66.
[52] A. Trampuz, A.F. Widmer, Infections associated with orthopedic implants, Current opinion in infectious diseases, 19 (2006) 349-356.
[53] C.B. Landersdorfer, J.B. Bulitta, M. Kinzig, U. Holzgrabe, F. Soergel, Penetration of antibacterials into bone, Clinical pharmacokinetics, 48 (2009) 89-124.
[54] D. Stengel, K. Bauwens, J. Sehouli, A. Ekkernkamp, F. Porzsolt, Systematic review and meta-analysis of antibiotic therapy for bone and joint infections, The Lancet infectious diseases, 1 (2001) 175-188.
[55] M.C. Birt, D.W. Anderson, E.B. Toby, J. Wang, Osteomyelitis: Recent advances in pathophysiology and therapeutic strategies, Journal of orthopaedics, 14 (2017) 45-52.
[56] H.v.d. Belt, D. Neut, W. Schenk, J.R.v. Horn, H.C.v.d. Mei, H.J. Busscher, Infection of orthopedic implants and the use of antibiotic-loaded bone cements: a review, Acta Orthopaedica Scandinavica, 72 (2001) 557-571.
[57] M.C. Chifiriuc, A.M. Holban, C. Curutiu, L.-M. Ditu, G. Mihaescu, A.E. Oprea, A.M. Grumezescu, V. Lazar, Antibiotic drug delivery systems for the intracellular targeting of bacterial pathogens, Smart Drug Delivery System, IntechOpen2016.
[58] S.B. Levy, B. Marshall, Antibacterial resistance worldwide: causes, challenges and responses, Nature medicine, 10 (2004) S122.
[59] J.T. Mader, M.E. Shirtliff, S.C. Bergquist, J. Calhoun, Antimicrobial treatment of chronic osteomyelitis, Clinical Orthopaedics and Related Research (1976-2007), 360 (1999) 47-65.
[60] L. Lazzarini, B.A. Lipsky, J.T. Mader, Antibiotic treatment of osteomyelitis: what have we learned from 30 years of clinical trials?, International journal of infectious diseases, 9 (2005) 127-138.
[61] N. Rao, B.H. Ziran, B.A. Lipsky, Treating osteomyelitis: antibiotics and surgery, Plastic and reconstructive surgery, 127 (2011) 177S-187S.
[62] N.C. Klein, B.A. Cunha, Tetracyclines, The Medical clinics of North America, 79 (1995) 789-801.
[63] S.A. Sassman, L.S. Lee, Sorption of three tetracyclines by several soils: assessing the role of pH and cation exchange, Environmental Science & Technology, 39 (2005) 7452-7459.
[64] I. Chopra, T. Howe, Bacterial resistance to the tetracyclines, Microbiological reviews, 42 (1978) 707.
[65] E. Michalova, P. Novotna, J. Schlegelova, Tetracyclines in veterinary medicine and bacterial resistance to them. A review, Veterinarni Medicina-UZPI (Czech Republic), (2004).
[66] M.E. Parolo, M.C. Savini, J.M. Valles, M.T. Baschini, M.J. Avena, Tetracycline adsorption on montmorillonite: pH and ionic strength effects, Applied Clay Science, 40 (2008) 179-186.
[67] M.L. Nelson, S.B. Levy, The history of the tetracyclines, Annals of the New York Academy of Sciences, 1241 (2011) 17-32.
[68] A.N. Sapadin, R. Fleischmajer, Tetracyclines: nonantibiotic properties and their clinical implications, Journal of the American Academy of Dermatology, 54 (2006) 258-265.
[69] S. Gholap, S. Banarjee, D. Gaikwad, S. Jadhav, R. Thorat, Hollow microsphere: A review, International Journal of Pharmaceutical Sciences Review and Research, 1 (2010) 74-79.
[70] O.C. Farokhzad, J. Cheng, B.A. Teply, I. Sherifi, S. Jon, P.W. Kantoff, J.P. Richie, R. Langer, Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo, Proceedings of the National Academy of Sciences, 103 (2006) 6315-6320.
[71] K. Kanellakopoulou, E.J. Giamarellos-Bourboulis, Carrier systems for the local delivery of antibiotics in bone infections, Drugs, 59 (2000) 1223-1232.
[72] M. Diefenbeck, T. Mückley, G.O. Hofmann, Prophylaxis and treatment of implant-related infections by local application of antibiotics, Injury, 37 (2006) S95-S104.
[73] C.G. Ambrose, G.R. Gogola, T.A. Clyburn, A.K. Raymond, A.S. Peng, A.G. Mikos, Antibiotic microspheres: preliminary testing for potential treatment of osteomyelitis, Clinical Orthopaedics and Related Research®, 415 (2003) 279-285.
[74] K. Uekama, F. Hirayama, T. Irie, Cyclodextrin drug carrier systems, Chemical reviews, 98 (1998) 2045-2076.
[75] S. Allababidi, J.C. Shah, Kinetics and mechanism of release from glyceryl monostearate‐based implants: Evaluation of release in a gel simulating in vivo implantation, Journal of pharmaceutical sciences, 87 (1998) 738-744.
[76] M. Yokoyama, Drug targeting with nano-sized carrier systems, Journal of Artificial Organs, 8 (2005) 77-84.
[77] Y.H. Yun, B.K. Lee, K. Park, Controlled drug delivery: historical perspective for the next generation, Journal of Controlled Release, 219 (2015) 2-7.
[78] P.I. Lee, J.X. Li, Evolution of oral controlled release dosage forms, Oral Controlled Release Formulation Design and Drug Delivery, John Wiley & Sons, Inc., Hoboken, NJ, (2010) 21-31.
[79] J.H. Lee, Y. Yeo, Controlled drug release from pharmaceutical nanocarriers, Chemical engineering science, 125 (2015) 75-84.
[80] R.A. Siegel, M.J. Rathbone, Overview of controlled release mechanisms, Fundamentals and Applications of Controlled Release Drug Delivery, Springer2012, pp. 19-43.
[81] K. Krishna, C. Reddy, S. Srikanth, A Review on Microsphere for Novel drug delivery System, Int J Res Pharm Chem, 3 (2013) 763-767.
[82] O. Felt, P. Buri, R. Gurny, Chitosan: a unique polysaccharide for drug delivery, Drug development and industrial pharmacy, 24 (1998) 979-993.
[83] T. Chandy, C.P. Sharma, Chitosan-as a biomaterial, Biomaterials, artificial cells and artificial organs, 18 (1990) 1-24.
[84] P.A. Sandford, J.P. Zikakis, C.J. Brine, Advances in chitin and chitosan, Elsevier Applied Science1992.
[85] L.L. Hench, The story of Bioglass®, Journal of Materials Science: Materials in Medicine, 17 (2006) 967-978.
[86] L.L. Hench, R.J. Splinter, W. Allen, T. Greenlee, Bonding mechanisms at the interface of ceramic prosthetic materials, Journal of biomedical materials research, 5 (1971) 117-141.
[87] A. Salinas, S. Shruti, G. Malavasi, L. Menabue, M. Vallet-Regí, Substitutions of cerium, gallium and zinc in ordered mesoporous bioactive glasses, Acta biomaterialia, 7 (2011) 3452-3458.
[88] A. Kirsten, A. Hausmann, M. Weber, J. Fischer, H. Fischer, Bioactive and thermally compatible glass coating on zirconia dental implants, Journal of dental research, 94 (2015) 297-303.
[89] W. Xia, J. Chang, Well-ordered mesoporous bioactive glasses (MBG): a promising bioactive drug delivery system, Journal of Controlled Release, 110 (2006) 522-530.
[90] J.K. Christie, J. Malik, A. Tilocca, Bioactive glasses as potential radioisotope vectors for in situ cancer therapy: investigating the structural effects of yttrium, Physical Chemistry Chemical Physics, 13 (2011) 17749-17755.
[91] A. Tilocca, Realistic models of bioactive glass radioisotope vectors in practical conditions: Structural effects of ion exchange, The Journal of Physical Chemistry C, 119 (2015) 27442-27448.
[92] W. Cao, L.L. Hench, Bioactive materials, Ceramics international, 22 (1996) 493-507.
[93] L.L. Hench, Bioceramics: from concept to clinic, Journal of the american ceramic society, 74 (1991) 1487-1510.
[94] A. Clark Jr, C. Pantano Jr, L. Hench, Auger spectroscopic analysis of bioglass corrosion films, Journal of the American Ceramic Society, 59 (1976) 37-39.
[95] R. Li, A. Clark, L. Hench, An investigation of bioactive glass powders by sol‐gel processing, Journal of Applied Biomaterials, 2 (1991) 231-239.
[96] S.-J. Shih, Y.-J. Chou, I.-C. Chien, One-step synthesis of bioactive glass by spray pyrolysis, Journal of Nanoparticle Research, 14 (2012) 1299.
[97] G.L. Messing, S.C. Zhang, G.V. Jayanthi, Ceramic powder synthesis by spray pyrolysis, Journal of the American Ceramic Society, 76 (1993) 2707-2726.
[98] Y.-J. Chou, C.-W. Hsiao, N.-T. Tsou, M.-H. Wu, S.-J. Shih, Preparation and in Vitro Bioactivity of Micron-sized Bioactive Glass Particles Using Spray Drying Method, Applied Sciences, 9 (2019) 19.
[99] L. Hench, Bioactive ceramics: Theory and clinical applications, Bioceramics, Elsevier1994, pp. 3-14.
[100] D.C. Greenspan, Bioactive glass: mechanisms of bone bonding, Tandläkartidningen Ǻrk, 91 (1999) 1-32.
[101] M. Lombardi, L. Gremillard, J. Chevalier, L. Lefebvre, I. Cacciotti, A. Bianco, L. Montanaro, A comparative study between melt-derived and sol-gel synthesized 45S5 bioactive glasses, Key Engineering Materials, Trans Tech Publ, 2013, pp. 15-30.
[102] P. Sepulveda, J.R. Jones, L.L. Hench, Characterization of melt‐derived 45S5 and sol‐gel–derived 58S bioactive glasses, Journal of Biomedical Materials Research: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, 58 (2001) 734-740.
[103] S.-J. Shih, Y.-Y. Wu, K.B. Borisenko, Control of morphology and dopant distribution in yttrium-doped ceria nanoparticles, Journal of Nanoparticle Research, 13 (2011) 7021-7028.
[104] C. Shih, H. Chen, L. Huang, P. Lu, H. Chang, I. Chang, Synthesis and in vitro bioactivity of mesoporous bioactive glass scaffolds, Materials Science and Engineering: C, 30 (2010) 657-663.
[105] S.-J. Shih, Y.-J. Chou, C.-Y. Chen, C.-K. Lin, One-step synthesis and characterization of nanosized bioactive glass, J. Med. Biol. Eng, 34 (2014) 18-23.
[106] C.-Y. Chen, Y.-R. Lyu, C.-Y. Su, H.-M. Lin, C.-K. Lin, Characterization of spray pyrolyzed manganese oxide powders deposited by electrophoretic deposition technique, Surface and Coatings Technology, 202 (2007) 1277-1281.
[107] S.-J. Shih, L.-Y.S. Chang, C.-Y. Chen, K.B. Borisenko, D.J. Cockayne, Nanoscale yttrium distribution in yttrium-doped ceria powder, Journal of Nanoparticle Research, 11 (2009) 2145-2152.
[108] K. Cal, K. Sollohub, Spray drying technique. I: Hardware and process parameters, Journal of pharmaceutical sciences, 99 (2010) 575-586.
[109] J. Broadhead, S. Edmond Rouan, C. Rhodes, The spray drying of pharmaceuticals, Drug development and industrial pharmacy, 18 (1992) 1169-1206.
[110] K. Masters, Spray drying handbook, Spray drying handbook., (1985).
[111] A. Sosnik, K.P. Seremeta, Advantages and challenges of the spray-drying technology for the production of pure drug particles and drug-loaded polymeric carriers, Advances in colloid and interface science, 223 (2015) 40-54.
[112] A.B.D. Nandiyanto, K. Okuyama, Progress in developing spray-drying methods for the production of controlled morphology particles: From the nanometer to submicrometer size ranges, Advanced Powder Technology, 22 (2011) 1-19.
[113] K. Sahil, M. Akanksha, S. Premjeet, A. Bilandi, B. Kapoor, Microsphere: A review, Int. J. Res. Pharm. Chem, 1 (2011) 1184-1198.
[114] F.Y. Alqahtani, F.S. Aleanizy, E.T. El, H.M. Alkahtani, B.T. AlQuadeib, Paclitaxel, Profiles of drug substances, excipients, and related methodology, 44 (2019) 205-238.
[115] S. Shanmugam, Granulation techniques and technologies: recent progresses, BioImpacts: BI, 5 (2015) 55.
[116] L.L. Augsburger, M.K. Vuppala, Theory of granulation, Drugs and the pharmaceutical sciences, 81 (1997) 7-24.
[117] B.J. Ennis, Theory of granulation: an engineering perspective, Handbook of pharmaceutical granulation technology, CRC Press2005, pp. 35-106.
[118] Z. Živcová, E. Gregorová, W. Pabst, D.S. Smith, A. Michot, C. Poulier, Thermal conductivity of porous alumina ceramics prepared using starch as a pore-forming agent, Journal of the European Ceramic Society, 29 (2009) 347-353.
[119] J.M. Harris, Poly (ethylene glycol) chemistry: biotechnical and biomedical applications, Springer Science & Business Media2013.
[120] H. Du, S. Bandara, L.E. Carson, R.R. Kommalapati, Association of Polyethylene Glycol Solubility with Emerging Membrane Technologies, Wastewater Treatment, and Desalination, Polyethylene Glycol, IntechOpen2019.
[121] J.M. Harris, S. Zalipsky, A.C.S. Staff, Poly (ethylene glycol), American Chemical Society Washington, DC1997.
[122] A.A. D’souza, R. Shegokar, Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications, Expert opinion on drug delivery, 13 (2016) 1257-1275.
[123] J. Jane, Starch properties, modifications, and applications, Journal of Macromolecular Science, Part A: Pure and Applied Chemistry, 32 (1995) 751-757.
[124] J.M. LeBeau, Y. Boonyongmaneerat, Comparison study of aqueous binder systems for slurry-based processing, Materials Science and Engineering: A, 458 (2007) 17-24.
[125] E. Gregorová, W. Pabst, Process control and optimized preparation of porous alumina ceramics by starch consolidation casting, Journal of the European Ceramic Society, 31 (2011) 2073-2081.
[126] H. Nishijima, R. Maki, Y. Suzuki, Microstructural control of porous Al2TiO5 by using potato starch as pore-forming agent, Journal of the Ceramic Society of Japan, 121 (2013) 730-733.
[127] H. Alves, G. Tarı, A. Fonseca, J. Ferreira, Processing of porous cordierite bodies by starch consolidation, Materials Research Bulletin, 33 (1998) 1439-1448.
[128] O. Lyckfeldt, J. Ferreira, Processing of porous ceramics by ‘starch consolidation’, Journal of the European Ceramic Society, 18 (1998) 131-140.
[129] E. Gregorová, W. Pabst, Porosity and pore size control in starch consolidation casting of oxide ceramics—achievements and problems, Journal of the European Ceramic Society, 27 (2007) 669-672.
[130] N. Hwang, A.R. Barron, BET surface area analysis of nanoparticles, The Connexions project, (2011) 1-11.
[131] T. Kokubo, H. Kushitani, S. Sakka, T. Kitsugi, T. Yamamuro, Solutions able to reproduce in vivo surface‐structure changes in bioactive glass‐ceramic A‐W3, Journal of biomedical materials research, 24 (1990) 721-734.
[132] M.F. Chung, W.T. Chia, H.Y. Liu, C.W. Hsiao, H.C. Hsiao, C.M. Yang, H.W. Sung, Inflammation‐Induced Drug Release by using a pH‐Responsive Gas‐Generating Hollow‐Microsphere System for the Treatment of Osteomyelitis, Advanced healthcare materials, 3 (2014) 1854-1861.
[133] J. Zhang, M. Zhao, X. Tian, X. Lv, Z. Chen, K. Zhou, X. Ren, P. Zhang, X. Mei, Protein-mediated mineralization of edaravone into injectable, pH-sensitive microspheres used for potential minimally invasive treatment of osteomyelitis, New Journal of Chemistry, 42 (2018) 5447-5455.
[134] B.-J. Hong, S.-J. Shih, Novel pore-forming agent to prepare of mesoporous bioactive glass using one-step spray pyrolysis, Ceramics International, 43 (2017) S771-S775.