5 research outputs found
향상된 경구 생체이용률을 위한 BCS class II 약물의 프로리포솜 적용 :
Get PDF학위논문 (석사)-- 서울대학교 대학원 : 약학대학 약학과 약제과학 전공, 2016. 2. 김대덕.Purpose. The aim of this study was to develop a simple preparation method of proliposomes (PLs) with a high lipid content, and to characterize and evaluate the BCS class II drug-loaded PLs (valsartan-loaded PLs (VSTPLs) and celecoxib-loaded PLs (CXBPLs)) in vitro and in vivo for their suitability for oral delivery.
Methods. Rotary evaporator and freeze dryer were used to prepare PLs. Maximum lipid contents of PLs which can form liposomes after reconstitution were determined. After loading drugs, the solid state of PLs was also characterized by scanning electron microscopy (SEM), powder X-ray diffractometer (PXRD) and differential scanning calorimetry (DSC). PLs were reconstituted with distilled water, and then were characterized by measuring the particle size, zeta potential, entrapment efficiency (EE), and drug content. Particle morphology of reconstituted liposomes was determined by transmission electron microscopy (TEM). In vitro dissolution and in vivo pharmacokinetics of PLs in rats were also evaluated.
Results. Phospholipid content of the PLs was increased up to 20% (w/w), thereby being able to enhance the drug loading content. Crystalline state of the drug was transformed to amorphous state during the preparation of PLs. Particle size of reconstituted VST-loaded liposomes and CXB-loaded liposomes were 369 ± 31 nm and 537 ± 10 nm with the zeta potential of -57.4 ± 0.4 mV and –64.2 ± 0.3 mV, respectively. The EE values of VST and CXB were 77.5 ± 2.8% and 84.7 ± 1.2% for VST-loaded liposomes and CXB-loaded liposomes, respectively. The rate and extent of dissolution of drugs from the PLs were higher than those of crude drug powder in various pHs. In pharmacokinetic studies after oral administration in rats, drugs in PLs showed higher Cmax values and 1.82-fold and 1.73-fold higher AUC values for VSTPLs and CXBPLs, respectively, than those from the drug powder. Shorter Tmax was shown in CXBPLs than that of crude drug powder.
Conclusions. The preparation method of PLs developed in this study has the following advantages compared with conventional preparation methods: (a) the preparation method is simple and could be easily scaled up, (b) the solvent system used has no toxicity concern, (c) the PLs have a higher lipid content, which can enhance the incorporation of poorly water-soluble drugs, (d) the rapid formation of liposomes in aqueous media and the amorphous state of the drug in PLs can increase solubility and dissolution rate, thereby increase oral bioavailability of the drug.1. Introduction 1
2. Materials and methods 4
2.1 Materials 4
2.2 Preparation of proliposomes (PLs) 4
2.3 Characterization of PLs 5
2.3.1 Solid state characterization 5
2.3.1.1 Field emission scanning electron microscopy (FESEM) 5
2.3.1.2 Differential scanning claorimetry (DSC) 5
2.3.1.3 Powder X-ray diffractometry (PXRD) 6
2.3.2 Characterization of liposomes 6
2.3.2.1 Tranmission electron microscopy (TEM) 6
2.3.2.2 Particle size and zeta potential 6
2.3.2.3 Determination of drug content and entrapment efficiency (EE) 7
2.4 In vitro dissolution studies 8
2.4.1 In vitro dissolution studies of VSTPLs 8
2.4.2 In vitro dissolution studies of CXBPLs 9
2.5 In vivo pharmacokinetic studies 10
2.5.1 In vivo pharmacokinetic studies of VSTPLs 10
2.5.2 In vivo pharmacokinetic studies of CXBPLs 11
2.5.3 Pharmacokinetic parameters 13
2.6 Statistical Analysis 13
3. Result and discussion 14
3.1 Preparation of proliposomes (PLs) 14
3.2 Characterization of PLs 15
3.2.1 Solid state characterization 15
3.2.2 Characterization of liposomes 17
3.3 In vitro dissolution studies 17
3.3.1 In vitro dissolution studies of VSTPLs 17
3.3.2 In vitro dissolution studies of CXBPLs 18
3.4 In vivo pharmacokinetic studies 19
3.4.1 In vivo pharmacokinetic studies of VSTPLs 19
3.4.2 In vivo pharmacokinetic studies of CXBPLs 20
4. Conclusions 22
5. References 23
Supplementary Information 40
국문초록 49Maste
(A)Simulation study of model selection : adaptive methods
No full textThesis(master`s)--서울대학교 대학원 :통계학과,2006.Maste
Induction of Long-Term Depression at Flocculus Purkinje Cells in Juvenile Mice
Get PDF학위논문 (석사)-- 서울대학교 대학원 : 의과학과 의과학 전공, 2013. 2. 김상정.Cerebellum is a brain region important in motor control. Cerebellum can be subdivided into cerebrocerebellum, spinocerebellum and vestibulocerebellum. Spinocerebellum receives inputs from spinal cord and auditory system, while vestibulocerebellum receives vestibular inputs from semicircular canals and vestibular nuclei. Vestibular ocular reflex (VOR) learning is usually used to test cerebellar functions. Flocculus, a part of vestibulocerebellum, is supposed to be the initial place of VOR learning and long-term depression (LTD) is the underlying mechanism for it. However, LTD had not been observed directly in floccular slices.
Here whole-cell recordings were made at lobules III to V of cerebellar vermis and lobule X and flocculus, which are known to be the spinocerebellum and vestibulocerebellum, respectively. Data were analyzed them for LTD and other electrophysiological properties. First, AMPA receptor-mediated fast excitatory post-synaptic current (EPSC) showed no difference in input-output curve and paired pulse ratio among three groups, meaning they have similar presynaptic properties. Second, Second, flocculus showed metabotropic glutamate receptor (mGluR)-mediated slow EPSC measured in the presence of NBQX and its amplitude was not significantly different from that in lobule III to V. However, lobule X which is also a part of vestibulocerebellum as flocculus, showed much smaller amplitude in slow EPSC. Third, it was possible to record LTD at flocculus with similar amplitude of LTD, while much smaller LTD was recorded from lobule X. The result suggests that LTD is normally induced at flocculus and it can be underlying cellular mechanisms for VOR learning.Abstract i
Contents iii
List of Figures iv
List of Abbreviations v
Introduction 1
Material and Methods 5
Results 10
Discussion 24
References 28
Abstract in Korean 32Maste
