Micro-syringe chip-guided intratumoral administration of lipid nanoparticles for targeted anticancer therapy

김정래,Sunejeong Song,곽민준,조한희,윤완수,황남철,Jinseong Kim,Jun Seo Lee,김동휘,김현철,전성익,김태일,김광명 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Nano-sized drug delivery system has been widely studied as a potential technique to promote tumorspecific delivery of anticancer drugs due to its passive targeting property, but resulting in very restricted improvements in its systemic administration so far. There is a requirement for a different approach that dramatically increases the targeting efficiency of therapeutic agents at targeted tumor tissues. Methods To improve the tumor-specific accumulation of anticancer drugs and minimize their undesirable toxicity to normal tissues, a tumor-implantable micro-syringe chip (MSC) with a drug reservoir is fabricated. As a clinically established delivery system, six liposome nanoparticles (LNPs) with different compositions and surface chemistry are prepared and their physicochemical properties and cellular uptake are examined in vitro. Subsequently, MSCguided intratumoral administration is studied to identify the most appropriate for the higher tumor targeting efficacy with a uniform intratumoral distribution. For efficient cancer treatment, pro-apoptotic anticancer prodrugs (SMAC-PFRRG- DOX) are encapsulated to the optimal LNPs (SMAC-P-FRRG-DOX encapsulating LNPs; ApoLNPs), then the ApoLNPs are loaded into the 1 μL-volume drug reservoir of MSC to be delivered intratumorally for 9 h. The tumor accumulation and therapeutic effect of ApoLNPs administered via MSC guidance are evaluated and compared to those of intravenous and intratumoral administration of ApoLNP in 4T1 tumor-bearing mice. Results MSC is precisely fabricated to have a 0.5 × 4.5 mm needle and 1 μL-volume drug reservoir to achieve the uniform intratumoral distribution of LNPs in targeted tumor tissues. Six liposome nanoparticles with different compositions of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (PC), 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (PS), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N-[methoxy (polyethylene glycol)2000] ( PEG2000-DSPE) are prepared with average sizes of 100–120 nm and loaded into the 1 μL-volume drug reservoir in MSC. Importantly negatively charged 10 mol% of PS-containing LNPs are very slowly infused into the tumor tissue through the micro-syringe of the MSC over 6 h. The intratumoral targeting efficiency of MSC guidance is 93.5%, effectively assisting the homogeneous diffusion of LNPs throughout the tumor tissue at 3.8- and 2.7-fold higher concentrations compared to the intravenous and intratumoral administrations of LNPs, respectively. Among the six LNP candidates 10 mol% of PS-containing LNPs are finally selected for preparing pro-apoptotic SMAC-P-FRRG-DOX anticancer prodrug-encapsulated LNPs (ApoLNPs) due to their moderate endocytosis rate high tumor accumulation and homogenous intratumoral distribution. The ApoLNPs show a high therapeutic effect specifically to cathepsin B-overexpressing cancer cells with 6.6 μM of IC50 value while its IC50 against normal cells is 230.7 μM. The MSC-guided administration of ApoLNPs efficiently inhibits tumor growth wherein the size of the tumor is 4.7- and 2.2-fold smaller than those treated with saline and intratumoral ApoLNP without MSC, respectively. Moreover, the ApoLNPs remarkably reduce the inhibitor of apoptosis proteins (IAPs) level in tumor tissues confirming their efficacy even in cancers with high drug resistance. Conclusion The MSC-guided administration of LNPs greatly enhances the therapeutic efficiency of anticancer drugs via the slow diffusion mechanism through micro-syringe to tumor tissues for 6 h, whereas they bypass most hurdles of systemic delivery including hepatic metabolism, rapid renal clearance, and interaction with blood components or other normal tissues, resulting in the minimum toxicity to normal tissues. The negatively charged ApoLNPs with cancer cell-specific pro-apoptotic prodrug (SMAC-P-FRRG-DOX) show the highest tumor-targeting efficacy when they are treated with the MSC guidance...

피부각질의 유지질상태에서 조절기능구조에 관한 연구

김정래,김혜주,Kim, Jeong-Lae,Kim, Hye-Ju 국제문화기술진흥원 2017 The Journal of the Convergence on Culture Technolo Vol.3 No.3

본 연구는 피부의 각질층에 분포되어 있는 유지질의 변화 상태를 조절하는 구조체계에 대해 고안한다. 피부구조에 유지질 성분이 어떻게 진행되는지 형태학으로 구성하였고, 주어진 세포사이와 세포횡단의 조건으로 기계적으로 조절되는 형태를 구성하였으며, 구조적인 기능으로 조절기능의 변화 상태를 확인하였다. 유지질 성분에서 피부의 모형을 구성하여 각층에 따른 유기질 상태의 피부 임피던스를 피부의 측정 임피던스 시스템으로 구성하여 진행하였다. 측정 임피던스는 ${\lambda}-Lip-RSC$, ${\lambda}-Lip-RSL$, ${\lambda}-Lip-CSG$, ${\lambda}-Lip-CSS$ 와 ${\lambda}-Lip-RSB$로 형성하였고, 세포사이와 세포횡단의 조건으로 변화의 차가 있고, 변환을 제어하는 전달시스템을 구성과 변환모델을 세분화하여 구축하였다. 앞으로 유지질 상태에서 피부의 기능적 효능조절이 가능한 유지질 성분의 조절시스템을 구성하여 지속적인 피부의 개선효과가 진행 될 것으로 예상된다. We are designed to control the lipoid variation of the structure system with the stratum corneum on the skin. The skin structure is consisted of a morphology how to use the lipoid component, and the given skin structure is consisted of the mechanical shapes of the intercellular route and transcellular route, and is confirmed to control the variation state of the structure capacity. The skin impedance is appeared to result the value of measurement such as shapes of ${\lambda}-Lip-RSC$, ${\lambda}-Lip-RSL$, ${\lambda}-Lip-CSG$, ${\lambda}-Lip-CSS$ and ${\lambda}-Lip-RSB$. The condition is showed to the alteration difference value of the intercellular route and transcellular route. And, composition condition is established to separate the division parts for conversion system that is constructed with the alteration modeling. We will be possible to progress the improvement effectiveness of the continuous skin control system on the skin.

외삽기법을 이용한 전리층 보정정보 영역 확장

김정래,김민규,Kim, Jeongrae,Kim, Mingyu 한국항공운항학회 2014 한국항공운항학회지 Vol.22 No.3

The coverage area of GNSS regional ionospheric correction model is mainly determined by the disribution of GNSS ground monitoring stations. Outside the coverage area, GNSS users may receive ionospheric correction signals but the correction does not contain valid correction information. Extrapolation of the correction information can extend the coverage area to some extent. Three interpolation methods, Kriging, biharmonic spline and cubic spline, are tested to evaluate the extrapolation accuracy of the ionospheric delay corrections outside the correction coverage area. IGS (International GNSS Service) ionosphere map data is used to simulate the corrections and to compute the extrapolation error statistics. Among the three methods, biharmonic method yields the best accuracy. The estimation error has a high value during Spring and Fall. The error has a high value in South and East sides and has a low value in North side.

Detection of the Popple Spot on the Pulse Variance of the Sonance

김정래,Hye-ju Kim,이기영 한국인터넷방송통신학회 2019 Journal of Advanced Smart Convergence Vol.8 No.1

Pulsation variance technique is blended the bumpy popple-sonance status of the brilliant-disparity understanding level (BDUL) on pulsation understanding gestalt. The understanding level condition by the pulsation understanding gestalt system is composed with the popple-sonance system. As to look for a two-node white-small dot of the brilliant situation, we are to take of the pulsation value with two-node white-small dot by the output signal. The concept of understanding level is composed the reference of brilliant-disparity level for variance signal by the pulsation sonance gestalt. Moreover indicating a bumpy variance of the BDUL of the maximum-minimum in terms of the popple-sonance gestalt, and pulsation two-node white-small dot sonance that was the a pulsation value of the far variance of the Pul-ug-FA-πMAX-MIN with 23.24±3.36 units, that was the a pulsation value of the convenient variance of the Pul-ug-CO-πMAX-MIN with 7.97±1.60 units, that was the a pulsation value of the flank variance of the Pul-ug-FL-πMAX-MIN with 3.02±0.47 units, that was the a pulsation value of the vicinage variance of the Pul-ug-VI-πMAX-MIN with 0.50±(-0.01) units. The popple sonance will be to evaluate at the bumpy ability of the popple-sonance gestalt with two-node white-small dot by the pulsation understanding level on the BDUL that is indicated the brilliant-disparity gestalt by the understanding level system. We will be possible to suppress of a gestalt by the special signal and to utilize a pulsation data of popple sonance level by the popple understanding system.

족관절 관절염이 있는 환자에서 체중 부하상태의 양측 족관절과 환측 족관절 전후면 방사선 사진의 방사선학적 측정치의 비교

김정래,이우천,Kim, Jung-Rae,Lee, Woo-Chun 대한족부족관절학회 2011 대한족부족관절학회지 Vol.15 No.3

Purpose: This study was performed to analyze the results of radiologic parameters between weight bearing affected single ankle anteroposterior (AP) view and both ankle AP view in ankle osteoarthritis (OA). Materials and Methods: Between January 2009 and August 2010, 41 patients (50 ankles) who visited our institution to treat ankle OA were reviewed retrospectively. In radiographic assessment, weight bearing affected single ankle AP view and both ankle AP view were checked, and measured tibial anterior surface angle (TAS), tibial medial malleolar angle (TMM), talar tilting angle (TT), maximum and minimun joint space width (JSW) of ankle, width between articular surface of medial malleolar and medial articular surface of talus as radiologic parameters. Results: On weight bearing both ankle AP view, TAS was $85.4{\pm}4.1^{\circ}$, TMM was $33.1{\pm}9^{\circ}$, TT was $5.4{\pm}6.1^{\circ}$, maximum JSW was $3.2{\pm}2.7$ mm, minimum JSW was $1.1{\pm}1.3$ mm, width between articular surface of medial malleolar and medial articular surface of talus was $1.8{\pm}1.8$ mm and on weight bearing affected ankle AP view, TAS was $85.3{\pm}3.9^{\circ}$, TMM was $34.3{\pm}10.9^{\circ}$, TT was $5.4{\pm}6.5^{\circ}$, maximum JSW was $3.2{\pm}2.7$ mm, minimum JSW was $1.1{\pm}1.3$ mm, width between articular surface of medial malleolar and medial articular surface of talus was $1.6{\pm}1.7$ mm. Conclusion: There is no statistical significance in radiologic parameters between weight-bearing affected single ankle AP view and both ankle AP view in ankle OA.

홈 네트워크 방식의 헬스 케어 시스템 구현

김정래,이우철,고윤석,Kim, Jeong-Lae,Lee, Woo-Chul,Ko, Yun-Seok 한국전자통신학회 2011 한국전자통신학회 논문지 Vol.6 No.6

본 논문에서는 인체의 운동 변화를 홈 네트워크 방식으로 측정하고 확인할 수 있는 헬스 케어 시스템을 구현하였다. 제안되는 시스템은 트레드밀 운동 또는 사이클 운동 자세에서, 그 운동의 변화에 따라 신호 전달 장치를 통하여 실시간으로 전달되는 생체 신호를 데이터 획득 장치를 통하여 얻고, 그 데이터를 분석 장치에서 논리적으로 분석하여 자세에 대한 평가를 할 수 있도록 구성하였다. 측정파라미터의 항목을 혈압(Blood Pressure), 온도(Temperature), 낙상(Fall Index), 무게분포도(WDI), 체질량지수(BMI) 등으로 함으로서 측정값을 통하여 신체적 변화정도를 확인하고, 신체의 상태를 평가할 수 있도록 감시 체제를 구성하였다. In this paper, a health care system is implemented which can identify the parameter for moving body after exercising based on home network. This system has catched a signal for physical condition of body data using data acquisition mechanism such as a data acquisition module, a data signal processing module and a feedback module. The composition has a functions of displacement point for a BMI and WDI, that the basic parameter measure to base on the heart rate, temperature. There are checked physical condition of body exercising to compounded a physical condition of sensory organ. There are to keep the lookout for the body condition that to estimate a health care with a physical organ through a exercise.

중소기업의 스마트팩토리 도입의도에 영향을 미치는 요인에 관한 연구 - 정부지원기대와 과업기술적합도를 포함하여

김정래,Kim, Joung-rae 한국벤처혁신학회 2020 벤처혁신연구 Vol.3 No.2

This study confirmed factors affecting smart factory technology acceptance through empirical analysis. It is a study on what factors have an important influence on the introduction of the smart factory, which is the core field of the 4th industry. I believe that there is academic and practical significance in the context of insufficient research on technology acceptance in the field of smart factories. This research was conducted based on the Unified Theory of Acceptance and Use of Technology (UTAUT), whose explanatory power has been proven in the study of the acceptance factors of information technology. In addition to the four independent variables of the UTAUT : Performance Expectancy, Effort Expectancy, Social Influence, and Facilitating Conditions, Government Assistance Expectancy, which is expected to be an important factor due to the characteristics of the smart factory, was added to the independent variable. And, in order to confirm the technical factors of smart factory technology acceptance, the Task Technology Fit(TTF) was added to empirically analyze the effect on Behavioral Intention. Trust is added as a parameter because the degree of trust in new technologies is expected to have a very important effect on the acceptance of technologies. Finally, empirical verification was conducted by adding Innovation Resistance to a research variable that plays a role as a moderator, based on previous studies that innovation by new information technology can inevitably cause refusal to users. For empirical analysis, an online questionnaire of random sampling method was conducted for incumbents of domestic small and medium-sized enterprises, and 309 copies of effective responses were used for empirical analysis. Amos 23.0 and Process macro 3.4 were used for statistical analysis. For accurate statistical analysis, the validity of Research Model and Measurement Variable were secured through confirmatory factor analysis. Accurate empirical analysis was conducted through appropriate statistical procedures and correct interpretation for causality verification, mediating effect verification, and moderating effect verification. Performance Expectancy, Social Influence, Government Assistance Expectancy, and Task Technology Fit had a positive (+) effect on smart factory technology acceptance. The magnitude of influence was found in the order of Government Assistance Expectancy(β=.487) > Task Technology Fit(β=.218) > Performance Expectancy(β=.205) > Social Influence(β=.204). Both the Task Characteristics and the Technology Characteristics were confirmed to have a positive (+) effect on Task Technology Fit. It was found that Task Characteristics(β=.559) had a greater effect on Task Technology Fit than Technology Characteristics(β=.328). In the mediating effect verification on Trust, a statistically significant mediating role of Trust was not identified between each of the six independent variables and the intention to introduce a smart factory. Through the verification of the moderating effect of Innovation Resistance, it was found that Innovation Resistance plays a positive (+) moderating role between Government Assistance Expectancy, and technology acceptance intention. In other words, the greater the Innovation Resistance, the greater the influence of the Government Assistance Expectancy on the intention to adopt the smart factory than the case where there is less Innovation Resistance. Based on this, academic and practical implications were presented.

'99년도 석유산업의 회고와 전망

김정래,Kim, Jeong-Rae 대한석유협회 1999 석유와 에너지 Vol.1999 No.11

세라믹스 분말 가압 성형 공정 변수설계(2부: 최적화)

김정래,금영탁,Kim J. L.,Keum Y. T. 한국결정성장학회 2005 韓國結晶成長學會誌 Vol.15 No.1

본 연구에서는 세라믹 제품의 고밀도를 얻기 위해 분말 압축 성형 공정 변수의 최적화가 수행되었다. 이를 위해 먼저 임의의 초기 밀도를 갖는 분말 성형체를 모델링하였다. 그리고 반복 가압 성형 공정시 상대밀도에 영향을 주는 Al₂O₃ 입자의 크기, 반복 가압 진폭 크기, 그리고 마찰계수에 따른 상대밀도의 변화를 유한요소법으로 해석하였다. 유한요소 해석 결과를 반응 표면법으로 수식화한 후, 격자 탐색법으로 가압 성형 공정 변수의 최적 조건을 찾았다. 입자의 크기가 22.5 ㎛, 반복 가압 진폭이 75 MPa, 마찰계수가 0.1103인 경우에 상대 밀도 값이 0.9390으로 최대가 되었다. In this study, the process parameters in ceramics powder compaction are optimized for getting high relative densities of ceramic products. To find optimized parameters, the analytic models of powder compaction are firstly prepared by 2-dimensional rod arrays with random green densities using a quasi-random multiparticle array. Then, using finite element method, the changes in relative densities are analyzed by varying the size of Al₂O₃ particle, the amplitude of cyclic compaction, and the coefficient of friction, which influence the relative density in cyclic compactions. After the analytic function of relative density associated process parameters are formulated by aid of the response surface method, the optimal conditions in powder compaction process are found by the grid search method. When the particle size of Al₂O₃ is 22.5 ㎛, the optimal parameters for the amplitude of cyclic compaction and the coefficient of friction are 75 MPa and 0.1103, respectively. The maximum relative density is 0.9390.

보습상태에서 피부각질의 구조 모델링에 관한 연구

김정래,김혜주,Kim, Jeong-Lae,Kim, Hye-Ju 국제문화기술진흥원 2017 The Journal of the Convergence on Culture Technolo Vol.3 No.3

We are made up to the variation of the structure modeling of the stratum corneum by the skin on the hydration. The given skin structure is consist of the control level of the intercellular route and transcellular route, and is confirmed to the variation of the modeling for algorithm. Hydration condition is consisted to modeling by the size, form and combination, that skin impedance is appeared to result the value of measurement by the several layer such as forms of ${\xi}-R-SC-RH$, ${\xi}-R-SL-RH$, ${\xi}-R-SG-RH$, ${\xi}-R-SS-RH$ and ${\xi}-R-SB-RH$. Hydration condition is showed to the alteration difference value of S-Corneum, S-Lucidum, S-Granulosum, S-Spinosum and S-Basale. And, composition condition was constructed with the alteration modeling that was established to separate the division parts for conversion system. We will be possible to progress the improvement effectiveness of the skin and to consist of the continuous hydration control system for functional on the skin. We will be possible to progress the improvement effectiveness of the skin and to consist of the continuous penetration control system for functional energy on the skin. 본 연구는 보습상태에서 피부의 각질층에 변화상태를 구조적으로 모델링한다. 피부구조에 따라 진행되는 형태는 세포사이와 세포횡단의 조건으로 조절 할 수 있도록 하였고, 구조적인 모델링으로 시스템의 변화상태를 확인하였다. 보습조건에서 크기 형태 조합의 모형을 구성하고, 결과적으로 보습상태의 피부 임피던스는 각층에 따라 피부에 측정 임피던스가 ${\xi}-R-SC-RH$, ${\xi}-R-SL-RH$, ${\xi}-R-SG-RH$, ${\xi}-R-SS-RH$ 와 ${\xi}-R-SB-RH$ 로 다른 형태로 나타났다. 보습조건에서 S-Corneum, S-Lucidum, S-Granulosum, S-Spinosum 과 S-Basale의 변화의 차가 있고, 변환을 제어하는 전달시스템을 구성과 변환모델을 세분화하여 구축하였다. 이를 통하여 보습상태에서 피부의 기능적 효능조절이 가능한 보습조절시스템이 구성되어 지속적인 피부의 개선효과가 진행 될 것으로 예상된다. 투과 조절시스템이 구성되어 지속적인 피부의 개선효과가 진행 될 것으로 예상된다.