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Cyclodextrins are Magician for Nanoparticles? Introduction: In last few years research and development of nanoscale systems became popular in pharmaceutical and biotechnological arena due to their associated potential applications in drug delivery and biotechnology.^1 Nanoparticles are small colloidal particles made of biodedgradable or nonbiodegradable materials. The general diameter nanoparticles ranges from 10 nm to 1000nm, but <200nm often refered as nanomedicine.^2 The drug is dissolved, dispersed, encapsulated, entrapped or attached to nanopartilce matrix.^3 ,^4 Depending on method of preparation, nanospheres (in which drug is uniformly dispersed in matrix) or nanocapsules (in which drug is confined in a cavity) are obtained which possess different properties and release characteristics suitable for best drug delivery or drug encapsulation. Error: Reference source not found,^5 On the account of their small size nanoparticles can penetrate into tissues an small capillaries and offer advantages including long circulation time, improvements in target to nontarget concentration, increased residence at target site and improved cellular uptake.^6 This is achieved by nanoparticles through macrophagic activation after their opsonization in bloodstream. The surface area per unit mass of nanoparticles compared to other particulates in unique characteristic feature which add ups to their functionality, which may be helpful in high solubility of drug candidate.^7 Various types of nanoparticulate systems were developed for drug delivery, including polymeric nanoparticles,^8 lipid nanoparticles (viz. first generation-solid lipid nanopartilcles and second generation-nanostructured lipid carriers),^9 polymeric micelles, liposome, nanotubes, nanocrystals, dendrimer, metallic nanoparticles,^10 quantum dots and magnetic nanoparticles.^11 Nanoparticles were employed for diverse applications, including site specific and targeted drug delivery in cancer as leaky and defective architecture of tumor allows interstitial access to nanoparticles which is popularly known as Enhanced permeation and retention.^12 ,^13 These are explored for drug delivery through different routes of administration incluidinhg oral, (^14) parenteral, (^15) pulmonary, ocular, (^16) brain (^17) and transdermal routes. 18 , 19
Despite the varied potential of nanoparticles, possess lacuna in some physicochemical and pharmaceutical aspects. The problems related to nanoparticulate drug delivery which are addressed in this review includes poor drug loading of loading of hydrophobic drugs, physical and chemical stability, safety and efficacy, pharmacokinetics and bioavailability related issues and modified drug release. Cyclodextrin : overview Cyclodextrins (CDs) are amphiphilic cyclic oligosaccharides containing at least 6 D-(+) glucopyranose units attached by α-(1, 4) glucosidic bonds. These are less commonly known as cyclomaltodextrins or cycloamyloses. Cyclodextrins are obtained from enzymatic degradation of starches obtained from potato, corn and other sources. This was discovered by French scientist who isolated crystalline compound called ‘cellulosine’ in 1891.^20 In following years a decade later role of Bacillus macerans was demonstrated by Austrian microbiologist Schardinger. Moreover, he also identified β-CD as ‘cellulosine’ depicted by Villiers.^21 ,^22 α, β and γ-Cyclodextrins with respectively 6, 7 and 8 glucopyranose units were included in the generally regarded as safe (GRAS) list of the FDA for use as a food additive in 2004, 2001 and 2000 respectively. Two important cyclodextrin derivatives hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of InactiveβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactive PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharmaceutical Ingredients used in novel pharmaceutical applications along with natural cyclodextrins.^23 The rationaly modifications of cyclodextrin molecule can be carried out for improving interaction with biological membrane by increasing their lipophilicity, improving interaction of hydrophobic drugs with CD and allowing self assembly of CD. Cyclodextrins were commonly used for aqueous solubility enhancement of drug for oral delivery and injectable delivery as result of their complexation ability.^24 They forms complexes with variety of molecules including organic, inorganic and organometallic compounds by so called molecular recognition phenomenon while their ability to form complexes with enantiomeric species is known as chiral recognition.^25 Cyclodextrins also found applications due to their versatile characteristics in drug permeability enhancement, bioavailability enhancement, improvement of safety and efficacy, improvement in drug and formulation stability, modified
Drug cyclodextrin complexes are prepared by method like colyophilization. Then this complex was dissolved in absolute ethanol (organic phase) and added to ultrapure water with stirring. If polymeric nanoparticles are to be prepared then polymer is dissolved in organic solvent and added to aqueous phase containing drug-CD complex with surfactant with stirring. Organic solvent is removed by evaporation with resultant nanoparticle formation.^33
- Inotropic Gelation: Alone sodium carboxy methyl β-CD (CM- β-CD)or with pentasodium tripolyphosphate (TPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of InactivePβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactive) in aqueous form was added to chitosan (CS) solution under magnetic stirring. The positively charged CS and negatively charged CM- β-CD and/or TPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of InactivePβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactive spontaneously react via inotropic gelation to form nanoparticles.^34 Utility of Cyclodextrin functinalized nanoparticles Nanoparticulate systems were employed for delivery of drugs as well as biomolecules. These systems pose various problems in drug or biomolecuels delivery. The major avenues in formulation of nanoparticulate systems where cyclodextrins can cause intervention are: A) Improvement of drug loading capacity The higher drug loading is usually expected in particulate systems. The free energy of host-guest complex is directly associated with binding constant and thus drug encapsulation. The physicochemical properties of drug viz. molecular mass, aqueous solubility, partition coefficient and K1:1 association constant and loading technique mainly affects drug loading in cyclodextrin functionaized nanoparticles.^35 ,^36 Drug loading can be improved by substituted semi synthetic cyclodextrins. Drug loading of paclitaxel was improved 500 times with 2-hydroxypropyl-beta-cyclodextrin^37 and 3 folds with 6- O-CAPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of InactiveRO-β-CD.^38 Drug loading of azole antifungal drugs was also improved with PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of InactiveEG-β-CD copolymer.^39 Encapsulation 6-coumarin in chitosan nanoparticles was improved with various cyclodextrins.^40 B) Stability Enhancement
Zeta potential and stability of nanoparticulate formulation is affected by type of excipients (usually by nature of polymers or lipid) and characteristics of alkyl chain in cyclodextrin molecule. It was demonstrated that sulfated β-CD associates with acylated CD to improve stability of nanospheres.^41 Nanosponges, a novel class of crosslinked cyclodextrin has shown to improve stability of lactone ring in camptothesin with resultant prolonged cytotoxic effect and enhanced safety.^42 C) Solubility profile Micelles formed from cholesteryl functionalized cyclodextrins with multiple potential drug binding site significantly enhance aqueous solubility of lipophilic drugs.^43 Camptothesin loading in cyclodextrin nanoparticles was higher as compared to polymeric nanoparticles, with its solubilization and stabilization.^44 Aqueous solubilization of fullerlane was reported using cyclodextrin functionlized dendrimers.^45 D) Safety and Efficacy Aspects Improved safety with equivalent efficacy of cyclodextrin nanoparticles was established by hemolytic and cytotoxicity studies.^46 Docetaxel entrapped in a heptakis (2-O- oligo(ethyleneoxide)-6-hexadecylthio-)-beta-CD has improved safety profile as compared to its commercial formulation taxotere.^47 Cyclodextrin functionlized nanoparticles were reported with promising safety and efficacy for anticancer drug tubulysin.^48 It was demonstrated that α-methyl prednisolone conjugated cyclodextrin polymer nanoparticles significantly decrease arthritis score in animals which could be a safer and effective approach for rheumatoid arthritis treatment.^49 Lower minimum inhibitory values were observed for azole antifungals compared to their ethanolic solution indicating increased efficacy by nanopspheres of cyclodextrin drug inclusion complexes.^50 Moreover use of modified cyclodextrins reduce/eliminate need of surfactant in nanoparticle preparation further improving their intravenous safety. 51 ,^52 E) Augmentation of drug absorption, permeability and bioavailability^53 Insulin loaded polysaccharide nanoparticles were developed with CD and chitosan which has potential to transport across nasal barrier. These nanoparticles significantly decrease plasma
Table 1 Factors affecting In vitro properties of cyclodextrin nanoparticles. Nanoparticle property Influential Factors Particle size Cyclodextrin substitution, chain length and nature, PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactivereparation technique Drug loading and release Drug solubility (aqueous), K1:1 association constant, PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveartition coefficient, Molecular weight, PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactivereparation technique
(^1) Insert atleast 10 title related to drug delivery and biotech (^2) Rajesh Singh a, James W. Lillard Jr. Nanoparticle-based targeted drug delivery, Experimental and Molecular PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveathology 86 (2009) 215–223 (2) (^3) Ellias Fattal Drug delivery : Nanoparticles In:James swabrik (Eds.)Encyclopedia of pharmaceutical technology Vol.2, Informa Healthcare USA, Inc., Newyork 2007 pp. (^4) Mehrdad Hamidi, Amir Azadi , PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveedram Rafiei, Hydrogel nanoparticles in drug delivery Advanced Drug Delivery Reviews 60 (2008) 1638– (^5) S.K. Sahoo, V. Labhasetwar, Nanotech approaches to drug delivery and imaging, Drug Discov. Today 8 (2003) 1112–1120. (^6) Anca N. Jătariu, Marcel PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveopa, and Cătălina A. PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveeptu , Diferent particulate systems—bypass the biological barriers? Journal of Drug Targeting, 2010; 18(4): 243– (^7) R.B. Gupta, U.B. Kompella, Nanoparticulate technology for drug delivery, Taylor and Francis, Newyork, pp. 1-18. (^8) Chiellini F, Bartoli C, Dinucci D, PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveiras AM, Anderson R, Croucher T., Bioeliminable polymeric nanoparticles for proteic drug delivery. 190. Int J PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharm. 2007 Oct 1;343(1-2):90-7. Epub 2007 May 16. (^9) Jana PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveardeike, Aiman Hommoss, Rainer H. Müller, Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products, International Journal of PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharmaceutics 366 (2009) 170– (^10) Marcato PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of InactiveD, Durán N., New aspects of nanopharmaceutical delivery systems., J Nanosci Nanotechnol. 2008 May;8(5):2216- (^11) Hayashi K, Ono K, Suzuki H, Sawada M, Moriya M, Sakamoto W, Yogo T., High-frequency, magnetic-field-responsive drug release from magnetic nanoparticle/organic hybrid based on hyperthermic effect., 16. ACS Appl Mater Interfaces. 2010 Jul;2(7):1903-11. (^12) Ho Lun Wong, Reina Bendayan, Andrew M. Rauth, Yongqiang Li, Xiao Yu Wu, Nanoparticle and targeted systems for cancer therapy, Advanced Drug Delivery Reviews 59 (2007) 491–504. (^13) James D. Byrne, Tania Betancourt, Lisa Brannon-PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveeppas, Active targeting schemes for nanoparticle systems in cancer therapeutics, Advanced Drug Delivery Reviews 60 (2008) 1615–
(^14) Soares AF, Carvalho Rde A, Veiga F. Oral administration of peptides and proteins: nanoparticles and cyclodextrins as biocompatible delivery systems. Nanomedicine (Lond). 2007 Apr;2(2):183-
(^15) Medha D. Joshi , Rainer H. Müller Lipid nanoparticles for parenteral delivery of actives, European Journal of PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharmaceutics and Biopharmaceutics 71 (2009) 161– (^16) Nagarwal RC, Kant S, Singh PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of InactiveN, Maiti PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactive, PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveandit JK, PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveolymeric nanoparticulate system: a potential approach for ocular drug delivery, J Control Release. 2009 May 21;136(1):2-13. Epub 2009 Feb 3 (^17) Jean-Christophe Olivier, Drug Transport to Brain with Targeted Nanoparticles, NeuroRx _ : The Journal of the American Society for Experimental NeuroTherapeutics Vol. 2, 108–119, January 2005, (^18) Gregor Cevc, Ulrich Vierl, Nanotechnology and the transdermal route A state of the art review and critical appraisal Journal of Controlled Release 141 (2010) 277– (^19) Yashwant Pathak, Deepak Thassu, and Michel Deleer, Nanoparticulate Drug Delivery Systems, Informa Healthcare USA, Inc. New York pp.185- (^20) Villiers, A. C. R. Acad. Sci. 1891 , 112 , 536–538. (^21) Schardinger, F., 1903. U¨ ber Thermophile Bakterien aus verschiedenen Speisen und Milch, sowie ¨uber einige Umsetzungsprodukte derselben in kohlenhydrathaltigen N¨ahrl¨osungen, darunter krystallisierte PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveolysaccharide (Dextrine) aus St¨arke. Z. Untersuch. Nahr. u. Genussm. 6, 865–880. (^22) Schardinger, F., 1911. Bildung kristallisierter PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveolysaccharide (Dextrine) aus St¨arkekleister durch Microben. Zentralbl. Bakteriol. PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactivearasitenk. Abt. II 29, 188–197.
(^38) Bilensoy E, Gürkaynak O, Ertan M, Sen M, Hincal AA., Development of nonsurfactant cyclodextrin nanoparticles loaded with anticancer drug paclitaxel. J PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharm Sci. 2008 Apr;97(4):1519-29. (^39) Memişoğlu E, Bochot A, Ozalp M, Sen M, Duchêne D, Hincal AA. , Direct formation of nanospheres from amphiphilic beta-cyclodextrin inclusion complexes. PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharm Res. 2003 Jan;20(1):117-25. (^40) Trapani A, Sitterberg J, Bakowsky U, Kissel T. The potential of glycol chitosan nanoparticles as carrier for low water soluble drugs. Int J PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharm. 2009 Jun 22;375(1-2):97-106. Epub 2009 Apr 11. (^41) Abdelwahed W, Degobert G, Dubes A, PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactivearrot-Lopez H, Fessi H., Sulfated and non-sulfated amphiphilic-beta-cyclodextrins: impact of their structural properties on the physicochemical properties of nanoparticles. Int J PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharm. 2008 Mar 3;351(1-2):289-95. Epub 2007 Oct 2. (^42) Shankar Swaminathan ,Linda PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveastero ,Loredana Serpe ,Francesco Trotta ,PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveradeep Vavia,Dino Aquilano, Michele Trotta, Gian PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveaolo Zara, Roberta Cavalli, Cyclodextrin-based nanosponges encapsulating camptothecin: PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactivehysicochemical characterization, stability and cytotoxicity. European Journal of PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharmaceutics and Biopharmaceutics 74 (2010) 193–201. (^43) Wang T, Chipot C, Shao X, Cai W. Structural characterization of micelles formed of cholesteryl- functionalized cyclodextrins. Langmuir. 2011 Jan 4;27(1):91-7. Epub 2010 Dec 9. (^44) Cirpanli Y, Bilensoy E, Lale Doğan A, Caliş S. Comparative evaluation of polymeric and amphiphilic cyclodextrin nanoparticles for effective camptothecin delivery. Eur J PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharm Biopharm. 2009 Sep;73(1):82-9. Epub 2009 May 13. (^45) Kojima C, Toi Y, Harada A, Kono K. Aqueous solubilization of fullerenes using poly(amidoamine) dendrimers bearing cyclodextrin and poly(ethylene glycol). Bioconjug Chem. 2008 Nov 19;19(11):2280-4. (^46) Bilensoy E, Gürkaynak O, Doğan AL, Hincal AA. Safety and efficacy of amphiphilic beta- cyclodextrin nanoparticles for paclitaxel delivery. Int J PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharm. 2008 Jan 22;347(1-2):163-70. Epub 2007 Jul 5. (^47) Quaglia F, Ostacolo L, Mazzaglia A, Villari V, Zaccaria D, Sciortino MT. The intracellular effects of non-ionic amphiphilic cyclodextrin nanoparticles in the delivery of anticancer drugs. Biomaterials. 2009 Jan;30(3):374-82. Epub 2008 Oct 17. (^48) Schluep T, Gunawan PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactive, Ma L, Jensen GS, Duringer J, Hinton S, Richter W, Hwang J. PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveolymeric tubulysin-peptide nanoparticles with potent antitumor activity. Clin Cancer Res. 2009 Jan 1;15(1):181-9. (^49) Jungyeon Hwang, Kathleen Rodgers, James C Oliver, Thomas Schluep, α -Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy, International Journal of Nanomedicine 2008:3(3) 359– (^50) Erem Memisoglu, Amelie Bochot, Meral Ozalp, Murat Sen, Dominique Duchene, and A. Atilla Hincal Direct Formation of Nanospheres from Amphiphilic Cyclodextrin Inclusion Complexes PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharmaceutical Research,n Vol.20, No.1, January2003, 117-125. (^51) Erem Memisoglu, Amelle Bochot, Murat Sen, Daniel Charon, Dominique Duchene, A. Atilla Hincal, Amphillic cyclodextrins modified on the primary face: Synthesis, characterization and evaluation of their potential as nove excipients in the preparation of nanocapsules. Jour of PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharm. Sci. 2002:91(5);1214-1224.
(^52) Erem Bilnsoy, Oya Gurkaynak, Mevlut Ertan, Murats E.N., A. Atilla Hincal, Development of Nonsurfactant Cyclodextrin Nanoparticles Loaded With Anticancer Drug PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveaclitaxel, Journal Of PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharmaceutical Sciences , 2008:(97)4;1519-1529. (^53) Klang V, Matsko N, Zimmermann AM, Vojnikovic E, Valenta C.Enhancement of stability and skin permeation by sucrose stearate and cyclodextrins in progesterone nanoemulsions. Int J PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharm. 2010 Jun 30;393(1-2):152-60. Epub 2010 Apr 29. (^54) Teijeiro-Osorio D, Remuñán-López C, Alonso MJ. New generation of hybrid poly/oligosaccharide nanoparticles as carriers for the nasal delivery of macromolecules. Biomacromolecules. 2009 Feb 9;10(2):243-9. (^55) S. Sajeesh, C.PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactive. Sharma, Cyclodextrin–insulin complex encapsulated polymethacrylic acid Based nanoparticles for oral insulin delivery.International Journal of PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharmaceutics 325 (2006) 147–154. (^56) Christine Vauthier, Isabelle Bertholon, and Denis Labarre, Integrated Development of Glycobiologics: From Discovery to Applications in the Design of Nanoparticular Drug Delivery Systems. In:Handbook of PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharmaceutical Biotechlogy Eds. Shayne Cox Gad 2007WILEY- INTERSCIENCE A John Wiley & Sons, Inc., pp. 130 (^57) Agüeros M, Areses PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactive, Campanero MA, Salman H, Quincoces G, PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveeñuelas I, Irache JM. Bioadhesive properties and biodistribution of cyclodextrin-poly(anhydride) nanoparticles. Eur J PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharm Sci. 2009 Jun 28;37(3-4):231-40. Epub 2009 Feb 28. (^58) Mura PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactive, Maestrelli F, Cecchi M, Bragagni M, Almeida A. Development of a new delivery system consisting in 'drug-in cyclodextrin-in PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of InactiveLGA nanoparticles'. J Microencapsul. 2010;27(6):479-86. (^59) Mohammad Mooguee, Yadollah Omidi, Soodabeh Davaran, Synthesisand In vitro Release of Adriamycin from Star-Shaped PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveoly(Lactide-co-Glycolide) Nano- and Microparticles. Journal Of PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharmaceutical Sciences , Vol.99, No.8, August 2010 (^60) Wang T, Zhang C, Liang XJ, Liang W, Wu Y. Hydroxypropyl-β-cyclodextrin copolymers and their nanoparticles as doxorubicin delivery system. J PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactiveharm Sci. 2011 Mar;100(3):1067-79. (^61) Jingou J, Shilei H, Weiqi L, Danjun W, Tengfei W, Yi X. PβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) were cited in the FDA's list of Inactivereparation, characterization of hydrophilic and hydrophobic drug in combine loaded chitosan/cyclodextrin nanoparticles and in vitro release study. Colloids Surf B Biointerfaces. 2011 Mar 1;83(1):103-7. Epub 2010 Nov 9 (^62) Davis ME. Design and development of IT-101, a cyclodextrin-containing polymer conjugate of camptothecin. Adv Drug Deliv Rev. 2009 Nov 12;61(13):1189-92. Epub 2009 Aug 12.
