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Yanbin Jiang - One of the best experts on this subject based on the ideXlab platform.
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self assembled nanospheres of folate decorated zein for the targeted delivery of 10 Hydroxycamptothecin
Industrial & Engineering Chemistry Research, 2017Co-Authors: Guijin Liu, Jiafeng Pang, Yunna Huang, Qiuling Xie, Guoqiang Guan, Yanbin JiangAbstract:Site-specific drug delivery is an effective approach to decreasing drug toxicity and enhancing therapeutic effects. In this study, zein was decorated with folic acid (FA) for targeted delivery of 10-Hydroxycamptothecin (HCPT). The reaction process was monitored using an online ATR-UV spectrophotometer, and the conjugation degree was quantified using a UV–vis spectrophotometer. Successful conjugation was evidenced using FT-IR and 1H NMR. The influence of FA conjugation on the self-assembly of zein molecules and cellular uptake was investigated in detail. FA conjugation facilitates the formation of small nanoparticles with good dispersity and stability and improves the cellular uptake in folate receptor positive cells. HCPT nanocrystals (NC) were prepared and incorporated into FA-zein. The drug release behavior of HCPT NC/FA-zein nanoparticles is more consistent with a diffusion mechanism than a matrix swelling/erosion mechanism of HCPT NC/zein particles; and HCPT NC/FA-zein nanoparticles induce higher anti...
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incorporation of 10 Hydroxycamptothecin nanocrystals into zein microspheres
Chemical Engineering Science, 2016Co-Authors: Guijin Liu, Yinxia Huang, Hongdi Wang, Yanbin JiangAbstract:Abstract Incorporation of drug nanocrystal (DNC) into a particulate carrier to form the DNC delivery system was conducted in this study, where 10-Hydroxycamptothecin (HCPT) was selected as the model drug and zein was the carrier. The supercritical anti-solvent (SAS) process or the built-in ultrasonic dialysis process (BUDP) was applied to prepare HCPT NC-loaded zein microspheres (HCPT NC-Zein MS) at first respectively, but the results showed that the products obtained were unsatisfactory in their particle microstructures. Fortunately, by combining the SAS process with BUDP, i.e. the co-precipitation of HCPT and zein prepared using the SAS process was dispersed into ethanol–water as the dialysis solution for BUDP, the results showed that desirable HCPT NC-Zein MS were obtained. The formulations were evaluated quantitatively by an overall desirability function (DF), and the optimized HCPT NC- Zein MS was prepared according to the range analysis results of DF. Under the optimized conditions, HCPT NC-Zein MS with a mean particle size=1.10±0.12 µm, drug loading=5.98% and encapsulation efficiency=95.68% were obtained. The further characterizations of SEM, FT-IR, XRD and DSC demonstrated that HCPT NC was successfully incorporated into the interior of zein microspheres. The effects of the process parameters and the formation mechanism of HCPT NC-Zein MS were discussed in detail. Furthermore, it is presented that HCPT NC-Zein MS sustained HCPT release rate successfully, where about 50% HCPT was fast released in the first 20 h, then the release trend followed zero order kinetics and reached 70% in 82 h.
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in vitro and in vivo anti tumor efficacy of 10 Hydroxycamptothecin polymorphic nanoparticle dispersions shape and polymorph dependent cytotoxicity and delivery of 10 Hydroxycamptothecin to cancer cells
Nanomedicine: Nanotechnology Biology and Medicine, 2016Co-Authors: Hongdi Wang, Yanbin Jiang, Guijin Liu, Jialing Feng, Baoqiong Chen, Qiuling XieAbstract:Abstract Nanotechnology associated with a crystal engineering approach was proposed for improving the solubility and efficacy of hydrophobic drugs in this study. 10-Hydroxycamptothecin polymorphic nanoparticle dispersions (HCPT-PNDs) were prepared using the supercritical anti-solvent technique coupled with the high-pressure homogenization method. Shape- and polymorph-dependent tumor suppression was observed in both in vitro and in vivo models, where needle-shaped HCPT-PND exhibited dramatic improvement of antitumor efficacy. A benefit of controllable size and a large surface-to-volume ratio of needle-shaped nanoparticles is the improvement of dissolution properties, which facilitates enhancing pharmacokinetic and pharmaco-dynamic properties. The needle-shaped HCPT-PND, which with longer blood retention time and more effective cellular uptake, makes it possible to accumulate drug in tumor tissues and exhibit higher cytotoxicity. No severe systemic toxicity was observed due to sustained-dissolution and the low dose of drug in normal tissues. The results suggest that the needle-shaped HCPT-PND is an interesting nano-formulation of HCPT. From the Clinical Editor Nanotechnology has enabled the production of novel therapeutics drugs against cancer. Here, the authors investigated the use of a crystal engineering approach for the modification of camptothecin in order to improve its water solubility. Physicochemical and biological properties were studied. The results would suggest the applicability of this approach for nano-formulation.
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preparation of 10 Hydroxycamptothecin proliposomes by the supercritical co2 anti solvent process
Chemical Engineering Journal, 2014Co-Authors: Guijin Liu, Wei Wang, Hongdi Wang, Yanbin JiangAbstract:Abstract For this study, 10-Hydroxycamptothecin proliposomes (HCPT-PL) were prepared using the supercritical CO2 anti-solvent process. The mixture of soy lecithin and cholesterol were chosen as liposomal components. The effects of different variables, i.e., the mass ratio of soy lecithin to cholesterol, the mass ratio of HCPT to liposomal components, temperature, pressure and HCPT solution flow rate on HCPT-PL formation were investigated using an OA25 (55) orthogonal experimental design. The formulations were evaluated quantitatively using an overall desirability function, which was calculated based on four assessment indices, i.e., particle size, particle size distribution, drug loading and encapsulation efficiency. SEM and TEM images showed that spherical or clavate HCPT-PL were obtained under different processing conditions, and the drug loading has a significant effect on the morphologies. Under the optimized conditions, clavate HCPT-PL with a mass median diameter of 209.8 ± 38.4 nm, a drug loading of 5.33% and an encapsulation efficiency of 85.28% were obtained. For the optimized HCPT-PL, the residual DCM meets the ICH requirement, and part of the encapsulated HCPT still maintains its crystalline state. And the result of in vitro release rate study showed that HCPT-PL sustained the HCPT release rate successfully, where the drug release of the optimized HCPT-PL followed the first order kinetics, and the drug diffusion mainly corresponded to a Fickian diffusion mechanism during the first 10 h.
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co precipitation of 10 Hydroxycamptothecin and poly l lactic acid by supercritical co2 anti solvent process using dichloromethane ethanol co solvent
Journal of Supercritical Fluids, 2013Co-Authors: Wei Wang, Guijin Liu, Yanbin JiangAbstract:Abstract In this study, 10-Hydroxycamptothecin (HCPT) and poly ( l -lactic acid) (PLLA) are co-precipitated by the supercritical anti-solvent (SAS) process using a mixture of dichloromethane (DCM)/ethanol (EtOH) as co-solvent, and supercritical carbon dioxide as the anti-solvent. The effect of five operating conditions on particle morphology, mass median diameter (Dp50) and HCPT loading is investigated using the single-factor method. The results indicate that HCPT loading can be greatly increased by using DCM/EtOH co-solvent, and the suitable operating conditions for the experimental system are determined. Under suitable conditions, the HCPT loading is 13.3% and Dp50 is 794.5 nm. The drug loaded microparticles are characterized in detail. The SEM images showed that most of the particles were spherical, and PLLA concentration has a major impact on the particle shape. Results of TEM, DSC and XRD indicate that the micronized HCPT is dispersed into the PLLA matrix. For low HCPT loading, most of HCPT existed in the drug loaded microparticles in an amorphous state, but for high HCPT loading, part of the encapsulated drug existed in crystalline form. FT-IR results show that SAS process does not change the chemical structure of HCPT. The result of in vitro drug release test indicated that the crystallinity of HCPT in microparticles affects the control release performance, and the good encapsulated microparticles with higher HCPT loading and higher crystallinity are better.
Zhonghua Zhang - One of the best experts on this subject based on the ideXlab platform.
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Design and Performance Evaluation of Ionic-Liquids-Based Microwave-Assisted Environmentally Friendly Extraction Technique for Camptothecin and 10-Hydroxycamptothecin from Samara of Camptotheca acuminata
2016Co-Authors: Shuya Wang, Chunjian Zhao, Lei Yang, Lin Zhang, Xiao-wei Sun, Zhonghua ZhangAbstract:Ionic-liquids-based, microwave-assisted extraction (ILMAE) was successfully applied to the extraction of two alkaloids: camptothecin (CPT) and 10-Hydroxycamptothecin (HCPT) from samara of Camptotheca acuminata. Ten different types of 1-alkyl-3-methylimidazolium, with different cations and anions, were investigated in this work, and 1-hexyl-3-methylimidazolium bromide ([C8MIM]Br) solution was selected as the optimal solvent. In addition, the extraction parameters, including ionic liquid concentration, soak time, microwave irradiation power, irradiation time, solid–liquid ratio, and number of extraction cycles, were optimized. The optimal conditions were as follows: 0.8 M [C8MIM]Br; soak time, 2 h; microwave irradiation power, 385 W; irradiation time, 8 min; solid–liquid ratio, 1:12 (g/mL); and two of extraction cycles. No degradation of the target analytes have been observed at the optimum conditions, as evidenced from the stability studies performed with standard CPT and HCPT. The proposed method also shows high reproducibility. Compared with the traditional methods, the proposed approach demonstrates higher efficiency in a shorter extraction time (from 4 h to 8 min), which demonstrates that ILMAE is a rapid, efficient, and simple sample extraction technique
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ionic liquid aqueous solution ultrasonic assisted extraction of camptothecin and 10 Hydroxycamptothecin from camptotheca acuminata samara
Chemical Engineering and Processing, 2012Co-Authors: Shuya Wang, Chunjian Zhao, Fengjian Yang, Yuangang Zu, Lei Yang, Lin Zhang, Zhonghua ZhangAbstract:Abstract In this paper, ionic liquid-aqueous solution ultrasonic-assisted extraction (ILUAE) has been successfully applied in extracting camptothecin and 10-Hydroxycamptothecin from Camptotheca acuminata samara. The ionic liquids with different cations and anions have been investigated, and 0.75 M 1-octyl-3-methylimidazolium bromide was selected as solvent. In addition, the ultrasonic parameters including ultrasonic power, time for ultrasonic treatment and solid–liquid ratio have been optimized by Response Surface Methodology. Compared with conventional solvent extraction, ILUAE exhibited higher efficiency (camptothecin increased by 13.96% and 10-Hydroxycamptothecin increased by 24.04%, respectively) and shorter extraction time (decreased from 6 h to 1.75 h for extracting three times), which indicated that ILUAE was an efficient, rapid and simple sample preparation technique.
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design and performance evaluation of ionic liquids based microwave assisted environmentally friendly extraction technique for camptothecin and 10 Hydroxycamptothecin from samara of camptotheca acuminata
Industrial & Engineering Chemistry Research, 2011Co-Authors: Shuya Wang, Chunjian Zhao, Yuangang Zu, Lei Yang, Lin Zhang, Zhonghua ZhangAbstract:Ionic-liquids-based, microwave-assisted extraction (ILMAE) was successfully applied to the extraction of two alkaloids: camptothecin (CPT) and 10-Hydroxycamptothecin (HCPT) from samara of Camptotheca acuminata. Ten different types of 1-alkyl-3-methylimidazolium, with different cations and anions, were investigated in this work, and 1-hexyl-3-methylimidazolium bromide ([C8MIM]Br) solution was selected as the optimal solvent. In addition, the extraction parameters, including ionic liquid concentration, soak time, microwave irradiation power, irradiation time, solid–liquid ratio, and number of extraction cycles, were optimized. The optimal conditions were as follows: 0.8 M [C8MIM]Br; soak time, 2 h; microwave irradiation power, 385 W; irradiation time, 8 min; solid–liquid ratio, 1:12 (g/mL); and two of extraction cycles. No degradation of the target analytes have been observed at the optimum conditions, as evidenced from the stability studies performed with standard CPT and HCPT. The proposed method also sho...
Lori J Latus - One of the best experts on this subject based on the ideXlab platform.
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the novel silatecan 7 tert butyldimethylsilyl 10 Hydroxycamptothecin displays high lipophilicity improved human blood stability and potent anticancer activity
Journal of Medicinal Chemistry, 2000Co-Authors: David Bom, Dennis P Curran, Stefan Kruszewski, Stephen G Zimmer, Thompson J Strode, Glenda Kohlhagen, Ashok J Chavan, Kimberly A Fraley, Alex L Bingcang, Lori J LatusAbstract:We describe the rational design and synthesis of B- and A,B-ring-modified camptothecins. The key α-hydroxy-δ-lactone pharmacophore in 7-tert-butyldimethylsilyl-10-Hydroxycamptothecin (DB-67, 14) displays superior stability in human blood when compared with clinically relevant camptothecin analogues. In human blood 14 displayed a t1/2 of 130 min and a percent lactone at equilibrium value of 30%. The tert-butyldimethylsilyl group renders the new agent 25-times more lipophilic than camptothecin, and 14 is readily incorporated, as its active lactone form, into cellular and liposomal bilayers. In addition, the dual 7-alkylsilyl and 10-hydroxy substitution in 14 enhances drug stability in the presence of human serum albumin. Thus, the net lipophilicity and the altered human serum albumin interactions together function to promote the enhanced blood stability. In vitro cytotoxicity assays using multiple different cell lines derived from eight distinct tumor types indicate that 14 is of comparable potency to campt...
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the novel silatecan 7 tert butyldimethylsilyl 10 Hydroxycamptothecin displays high lipophilicity improved human blood stability and potent anticancer activity
Journal of Medicinal Chemistry, 2000Co-Authors: David Bom, Dennis P Curran, Stefan Kruszewski, Stephen G Zimmer, Thompson J Strode, Glenda Kohlhagen, Ashok J Chavan, Kimberly A Fraley, Alex L Bingcang, Lori J LatusAbstract:We describe the rational design and synthesis of B- and A, B-ring-modified camptothecins. The key alpha-hydroxy-delta-lactone pharmacophore in 7-tert-butyldimethylsilyl-10-Hydroxycamptothecin (DB-67, 14) displays superior stability in human blood when compared with clinically relevant camptothecin analogues. In human blood 14 displayed a t(1/2) of 130 min and a percent lactone at equilibrium value of 30%. The tert-butyldimethylsilyl group renders the new agent 25-times more lipophilic than camptothecin, and 14 is readily incorporated, as its active lactone form, into cellular and liposomal bilayers. In addition, the dual 7-alkylsilyl and 10-hydroxy substitution in 14 enhances drug stability in the presence of human serum albumin. Thus, the net lipophilicity and the altered human serum albumin interactions together function to promote the enhanced blood stability. In vitro cytotoxicity assays using multiple different cell lines derived from eight distinct tumor types indicate that 14 is of comparable potency to camptothecin and 10-Hydroxycamptothecin, as well as the FDA-approved camptothecin analogues topotecan and CPT-11. In addition, cell-free cleavage assays reveal that 14 is highly active and forms more stable top1 cleavage complexes than camptothecin or SN-38. The impressive blood stability and cytotoxicity profiles for 14 strongly suggest that it is an excellent candidate for additional in vivo pharmacological and efficacy studies.
Chantal Guillemette - One of the best experts on this subject based on the ideXlab platform.
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the novel ugt1a9 intronic i399 polymorphism appears as a predictor of 7 ethyl 10 Hydroxycamptothecin glucuronidation levels in the liver
Drug Metabolism and Disposition, 2006Co-Authors: Hugo Girard, Lyne Villeneuve, Michael H Cou, Louischarles Fortie, Qi Hao, Lisa L Von Moltke, David J Greenbla, Chantal GuillemetteAbstract:Polymorphisms in UGT1A9 were associated with reduced toxicity and increased response to irinotecan in cancer patients. UDP-glucuronosyltransferase (UGT) protein expression, glucuronidation activities for 7-ethyl-10-Hydroxycamptothecin (SN-38), and probe substrates of the UGT1A9 and UGT1A1 were measured in 48 human livers to clarify the role of UGT1A9 variants on the in vitro glucuronidation of SN-38. Genotypes were assessed for UGT1A9 (–2152C>T, –275T>A, and –118T9>10), three novel UGT1A9 variants (–5366G>T, –4549T>C, and I399C>T), and UGT1A1 (–53TA6>7, –3156G>A, and –3279T>G). Of all the variants, the UGT1A9 I399C>T was associated with the most dramatic change in SN-38-glucuronide (SN-38G) (2.64-fold; p = 0.0007). Compared with UGT1A9 I399C/C, homozygous I399T/T presented elevated UGT1A1 and UGT1A9 proteins and higher glucuronidation of UGT1A9 and UGT1A1 substrates (p
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common human ugt1a polymorphisms and the altered metabolism of irinotecan active metabolite 7 ethyl 10 Hydroxycamptothecin sn 38
Molecular Pharmacology, 2002Co-Authors: Jeanfrancois Gagne, Patrick Bélanger, Valerie Montminy, Kim Journault, Genevieve Gaucher, Chantal GuillemetteAbstract:7-Ethyl-10-Hydroxycamptothecin (SN-38) is the pharmacologically active metabolite of irinotecan, in addition to being responsible for severe toxicity. Glucuronidation is the main metabolic pathway of SN-38 and has been shown to protect against irinotecan-induced gastrointestinal toxicity. The purpose of this study was to determine whether common polymorphic UDP-glucuronosyltransferase (UGT) affects SN-38 glucuronidation. First, kinetic characterization of SN-38-glucuronide (SN-38-G) formation was assessed for all known human UGT1A and UGT2B overexpressed in human embryonic kidney 293 cells. To assess the relative activity of UGT isoenzymes for SN-38, rates of formation of SN-38-G were monitored by liquid chromatography/mass spectrometry analysis and normalized by level of UGT cellular expression. Determination of intrinsic clearances predicts that hepatic UGT1A1 and UGT1A9 and the extrahepatic UGT1A7 are major components in SN-38-G formation, whereas a minor role is suggested for UGT1A6, UGT1A8, and UGT1A10. In support of the involvement of UGT1A9, a strong coefficient of correlation was observed in the glucuronidation of SN-38 and a substrate, mainly glucuronidate, by UGT1A9 (flavopiridol) by human liver microsomes (coefficient of correlation, 0.905; p = 0.002). In vitro functional experiments revealed a negative impact of the UGT1A1 allelic variants. Residual activities of 49, 7, 8, and 11% were observed for UGT1A1*6 (G71R), UGT1A1*27 (P229Q), UGT1A1*35 (L233R), and UGT1A1*7 (Y486D), respectively. Common variants of UGT1A7, UGT1A7*3 (N129K;R131K;W208R), and UGT1A7*4 (W208R), displayed residual activities of 41 and 28% compared with the UGT1A7*1 allele. Taken together, these data provide the evidence that molecular determinants of irinotecan response may include the UGT1A polymorphisms studied herein and common genetic variants of the hepatic UGT1A9 isoenzyme yet to be described.
Guijin Liu - One of the best experts on this subject based on the ideXlab platform.
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self assembled nanospheres of folate decorated zein for the targeted delivery of 10 Hydroxycamptothecin
Industrial & Engineering Chemistry Research, 2017Co-Authors: Guijin Liu, Jiafeng Pang, Yunna Huang, Qiuling Xie, Guoqiang Guan, Yanbin JiangAbstract:Site-specific drug delivery is an effective approach to decreasing drug toxicity and enhancing therapeutic effects. In this study, zein was decorated with folic acid (FA) for targeted delivery of 10-Hydroxycamptothecin (HCPT). The reaction process was monitored using an online ATR-UV spectrophotometer, and the conjugation degree was quantified using a UV–vis spectrophotometer. Successful conjugation was evidenced using FT-IR and 1H NMR. The influence of FA conjugation on the self-assembly of zein molecules and cellular uptake was investigated in detail. FA conjugation facilitates the formation of small nanoparticles with good dispersity and stability and improves the cellular uptake in folate receptor positive cells. HCPT nanocrystals (NC) were prepared and incorporated into FA-zein. The drug release behavior of HCPT NC/FA-zein nanoparticles is more consistent with a diffusion mechanism than a matrix swelling/erosion mechanism of HCPT NC/zein particles; and HCPT NC/FA-zein nanoparticles induce higher anti...
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incorporation of 10 Hydroxycamptothecin nanocrystals into zein microspheres
Chemical Engineering Science, 2016Co-Authors: Guijin Liu, Yinxia Huang, Hongdi Wang, Yanbin JiangAbstract:Abstract Incorporation of drug nanocrystal (DNC) into a particulate carrier to form the DNC delivery system was conducted in this study, where 10-Hydroxycamptothecin (HCPT) was selected as the model drug and zein was the carrier. The supercritical anti-solvent (SAS) process or the built-in ultrasonic dialysis process (BUDP) was applied to prepare HCPT NC-loaded zein microspheres (HCPT NC-Zein MS) at first respectively, but the results showed that the products obtained were unsatisfactory in their particle microstructures. Fortunately, by combining the SAS process with BUDP, i.e. the co-precipitation of HCPT and zein prepared using the SAS process was dispersed into ethanol–water as the dialysis solution for BUDP, the results showed that desirable HCPT NC-Zein MS were obtained. The formulations were evaluated quantitatively by an overall desirability function (DF), and the optimized HCPT NC- Zein MS was prepared according to the range analysis results of DF. Under the optimized conditions, HCPT NC-Zein MS with a mean particle size=1.10±0.12 µm, drug loading=5.98% and encapsulation efficiency=95.68% were obtained. The further characterizations of SEM, FT-IR, XRD and DSC demonstrated that HCPT NC was successfully incorporated into the interior of zein microspheres. The effects of the process parameters and the formation mechanism of HCPT NC-Zein MS were discussed in detail. Furthermore, it is presented that HCPT NC-Zein MS sustained HCPT release rate successfully, where about 50% HCPT was fast released in the first 20 h, then the release trend followed zero order kinetics and reached 70% in 82 h.
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in vitro and in vivo anti tumor efficacy of 10 Hydroxycamptothecin polymorphic nanoparticle dispersions shape and polymorph dependent cytotoxicity and delivery of 10 Hydroxycamptothecin to cancer cells
Nanomedicine: Nanotechnology Biology and Medicine, 2016Co-Authors: Hongdi Wang, Yanbin Jiang, Guijin Liu, Jialing Feng, Baoqiong Chen, Qiuling XieAbstract:Abstract Nanotechnology associated with a crystal engineering approach was proposed for improving the solubility and efficacy of hydrophobic drugs in this study. 10-Hydroxycamptothecin polymorphic nanoparticle dispersions (HCPT-PNDs) were prepared using the supercritical anti-solvent technique coupled with the high-pressure homogenization method. Shape- and polymorph-dependent tumor suppression was observed in both in vitro and in vivo models, where needle-shaped HCPT-PND exhibited dramatic improvement of antitumor efficacy. A benefit of controllable size and a large surface-to-volume ratio of needle-shaped nanoparticles is the improvement of dissolution properties, which facilitates enhancing pharmacokinetic and pharmaco-dynamic properties. The needle-shaped HCPT-PND, which with longer blood retention time and more effective cellular uptake, makes it possible to accumulate drug in tumor tissues and exhibit higher cytotoxicity. No severe systemic toxicity was observed due to sustained-dissolution and the low dose of drug in normal tissues. The results suggest that the needle-shaped HCPT-PND is an interesting nano-formulation of HCPT. From the Clinical Editor Nanotechnology has enabled the production of novel therapeutics drugs against cancer. Here, the authors investigated the use of a crystal engineering approach for the modification of camptothecin in order to improve its water solubility. Physicochemical and biological properties were studied. The results would suggest the applicability of this approach for nano-formulation.
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preparation of 10 Hydroxycamptothecin proliposomes by the supercritical co2 anti solvent process
Chemical Engineering Journal, 2014Co-Authors: Guijin Liu, Wei Wang, Hongdi Wang, Yanbin JiangAbstract:Abstract For this study, 10-Hydroxycamptothecin proliposomes (HCPT-PL) were prepared using the supercritical CO2 anti-solvent process. The mixture of soy lecithin and cholesterol were chosen as liposomal components. The effects of different variables, i.e., the mass ratio of soy lecithin to cholesterol, the mass ratio of HCPT to liposomal components, temperature, pressure and HCPT solution flow rate on HCPT-PL formation were investigated using an OA25 (55) orthogonal experimental design. The formulations were evaluated quantitatively using an overall desirability function, which was calculated based on four assessment indices, i.e., particle size, particle size distribution, drug loading and encapsulation efficiency. SEM and TEM images showed that spherical or clavate HCPT-PL were obtained under different processing conditions, and the drug loading has a significant effect on the morphologies. Under the optimized conditions, clavate HCPT-PL with a mass median diameter of 209.8 ± 38.4 nm, a drug loading of 5.33% and an encapsulation efficiency of 85.28% were obtained. For the optimized HCPT-PL, the residual DCM meets the ICH requirement, and part of the encapsulated HCPT still maintains its crystalline state. And the result of in vitro release rate study showed that HCPT-PL sustained the HCPT release rate successfully, where the drug release of the optimized HCPT-PL followed the first order kinetics, and the drug diffusion mainly corresponded to a Fickian diffusion mechanism during the first 10 h.
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co precipitation of 10 Hydroxycamptothecin and poly l lactic acid by supercritical co2 anti solvent process using dichloromethane ethanol co solvent
Journal of Supercritical Fluids, 2013Co-Authors: Wei Wang, Guijin Liu, Yanbin JiangAbstract:Abstract In this study, 10-Hydroxycamptothecin (HCPT) and poly ( l -lactic acid) (PLLA) are co-precipitated by the supercritical anti-solvent (SAS) process using a mixture of dichloromethane (DCM)/ethanol (EtOH) as co-solvent, and supercritical carbon dioxide as the anti-solvent. The effect of five operating conditions on particle morphology, mass median diameter (Dp50) and HCPT loading is investigated using the single-factor method. The results indicate that HCPT loading can be greatly increased by using DCM/EtOH co-solvent, and the suitable operating conditions for the experimental system are determined. Under suitable conditions, the HCPT loading is 13.3% and Dp50 is 794.5 nm. The drug loaded microparticles are characterized in detail. The SEM images showed that most of the particles were spherical, and PLLA concentration has a major impact on the particle shape. Results of TEM, DSC and XRD indicate that the micronized HCPT is dispersed into the PLLA matrix. For low HCPT loading, most of HCPT existed in the drug loaded microparticles in an amorphous state, but for high HCPT loading, part of the encapsulated drug existed in crystalline form. FT-IR results show that SAS process does not change the chemical structure of HCPT. The result of in vitro drug release test indicated that the crystallinity of HCPT in microparticles affects the control release performance, and the good encapsulated microparticles with higher HCPT loading and higher crystallinity are better.
