• Title/Summary/Keyword: Drug Delivery System

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Transdermal Delivery of Bufexamac using Microneedle System (마이크로니들시스템을 이용한 부펙사막의 경피전달)

  • Mo, Jong Hyun;Kim, Yun Tae;Park, Jung Soo;Lee, Jun Hee;Lee, Tae-Wan;Khang, Gilson;Rhee, John Moon;Lee, Han-Koo;Lee, Hai Bang
    • Korean Chemical Engineering Research
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    • v.46 no.2
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    • pp.211-216
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    • 2008
  • Bufexamac which was used for treatment of atopic dermatitis is the drug which was made as the ointment. However, penetration rate of bufexamac was very low for the barrier effect of stratum corneum. Microneedle was used to increase transdermal delivery rate of the bufexamac. We tried to conjugate bufexamac and FITC for the detection of penetration rate of bufexamac. FITC-bufexamac was mixed in hydrogel for the treatment skin surface. Fluorescent spectrophotometer was used to analysis the concentration of FITC-bufexamac. Microscope using fluorescent filter was used to capture the image about location of FITC-bufexamac in the skin. We confirmed that permeation rate of bufexamac was increased with the treatment by microneedle and was increased by the increasing number treatment of microneedle.

Recombinant Human Epidermal Growth Factor (rhEGF)-loaded Solid Lipid Nanoparticles: Fabrication and Their Skin Accumulation Properties for Topical rhEGF Delivery

  • Hwang, Hee-Jin;Han, Sunhui;Jeon, Sangok;Seo, Joeun;Oh, Dongho;Cho, Seong-Wan;Choi, Young Wook;Lee, Sangkil
    • Bulletin of the Korean Chemical Society
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    • v.35 no.8
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    • pp.2290-2294
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    • 2014
  • For the present study, rhEGF was encapsulated into solid lipid nanoparticles (SLNs). The SLNs were prepared by the $W_1/O/W_2$ double emulsification method combined with the high pressure homogenization method and the physical properties such as particle size, zeta-potential and encapsulation efficiency were measured. The overall particle morphology of SLNs was investigated using a transmission electron microscopy (TEM). The percutaneous skin permeation and accumulation property of rhEGF was evaluated using Franz diffusion cell system along with confocal laser scanning microscopy (CLSM). The mean particle size of rhEGF-loaded SLNs was $104.00{\pm}3.99nm$ and the zeta-potential value was in the range of -$36.99{\pm}0.54mV$, providing a good colloidal stability. The TEM image revealed a spherical shape of SLNs about 100 nm and the encapsulation efficiency was $18.47{\pm}0.22%$. The skin accumulation of rhEGF was enhanced by SLNs. CLSM image analysis provided that the rhEGF rat skin accumulation is facilitated by an entry of SLNs through the pores of skin.

3D Printing-Based Ultrafast Mixing and Injecting Systems for Time-Resolved Serial Femtosecond Crystallography (시간 분해 직렬 펨토초 결정학을 위한 3차원 프린팅 기반의 초고속 믹싱 및 인젝팅 시스템)

  • Ji, Inseo;Kang, Jeon-Woong;Kim, Taeyung;Kang, Min Seo;Kwon, Sun Beom;Hong, Jiwoo
    • Korean Chemical Engineering Research
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    • v.60 no.2
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    • pp.300-307
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    • 2022
  • Time-resolved serial femtosecond crystallography (TR-SFX) is a powerful technique for determining temporal variations in the structural properties of biomacromolecules on ultra-short time scales without causing structure damage by employing femtosecond X-ray laser pulses generated by an X-ray free electron laser (XFEL). The mixing rate of reactants and biomolecule samples, as well as the hit rate between crystal samples and x-ray pulses, are critical factors determining TR-SFX performance, such as accurate image acquisition and efficient sample consumption. We here develop two distinct sample delivery systems that enable ultra-fast mixing and on-demand droplet injecting via pneumatic application with a square pulse signal. The first strategy relies on inertial mixing, which is caused by the high-speed collision and subsequent coalescence of droplets ejected through a double nozzle, while the second relies on on-demand pneumatic jetting embedded with a 3D-printed micromixer. First, the colliding behaviors of the droplets ejected through the double nozzle, as well as the inertial mixing within the coalesced droplets, are investigated experimentally and numerically. The mixing performance of the pneumatic jetting system with an integrated micromixer is then evaluated by using similar approaches. The sample delivery system devised in this work is very valuable for three-dimensional biomolecular structure analysis, which is critical for elucidating the mechanisms by which certain proteins cause disease, as well as searching for antibody drugs and new drug candidates.

Au Electrode Characteristics and Fabrication of Si Drug Reservoirs for a Transdermal Drug Delivery System (경피 약물전달시스템을 위한 약물 저장용 Si 구조물 제작 및 Au 전극 특성)

  • Song, Tae-Eun;Kim, Dong-Bok;Han, Seung-Ho;Kim, Sang-Bum;Lee, Byoung-Kab;Oh, Sang-Woo;Yang, Sang-Sik;Pak, Jung-Ho
    • Proceedings of the KIEE Conference
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    • 2004.07c
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    • pp.2143-2145
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    • 2004
  • 본 논문은 미세공정을 이용하여 다중전극을 배열하여 전압 인가에 의해 선택적으로 약물 방출이 가능한 구역화된 약물 저장용 구조물의 설계 및 제작에 관한 것이다. 두께 525${\mu}m$ 언 (100) Si wafer를 이용하여 TMAH 용액의 조성 및 온도에 따라 Si 식각 기초실험을 하고 그 결과를 이용하여 최적 식각조건을 설정하였다. 구조물 opening 크기를 다양하게 설계하여 미량의 약물을 선택적으로 방출할 수 있게 하고자 역 피라미드 형태의 약물 저장용 구조물을 제작하였다. 전압 인가에 의한 약물 방출시 Au 전극의 특성을 고찰하고자 저장 구조물 위에 anode의 면적과 anode 전극간 거리를 변화시켜서 설계 및 제작하였고, polyimide를 전극 사이의 절연막으로 이용하였다. 제작된 구조품의 전극 특성은 5V의 설정전압을 인가하였을 경우 2500s 동안 0.25mA로 안정적으로 유지되었으나 10V, 15V, 20V일 경우 전극의 산화현상으로 Au 전극이 부식이 되어 전류가 안정적으로 흐르지 않는 것을 알 수 있었으며, 약물전달시스템에서 안정적인 전류 공급을 위해서는 Au 전극이 산화 되지 않는 전압 인가 조건 및 시간은 설정해야 함을 알 수 있었다.

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Recent Advancements of Treatment for Leptomeningeal Carcinomatosis

  • Gwak, Ho-Shin;Lee, Sang Hyun;Park, Weon Seo;Shin, Sang Hoon;Yoo, Heon;Lee, Seung Hoon
    • Journal of Korean Neurosurgical Society
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    • v.58 no.1
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    • pp.1-8
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    • 2015
  • Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques.

Direct Action of Genistein on the Hypothalamic Neuronal Circuits in Female Rats

  • Lee, Woo-Cheol;Lee, Sung-Ho
    • Development and Reproduction
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    • v.14 no.1
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    • pp.35-41
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    • 2010
  • Mammalian reproduction is regulated by a feedback circuit of the key reproductive hormones such as GnRH, gonadotropin and sex steroids on the hypothalamic-pituitary-gonadal axis. In particular, the onset of female puberty is triggered by gain of a pulsatile pattern and increment of GnRH secretion from hypothalamus. Previous studies including our own clearly demonstrated that genistein (GS), a phytoestrogenic isoflavone, altered the timing of puberty onset in female rats. However, the brain-specific actions of GS in female rats has not been explored yet. The present study was performed to examine the changes in the activities of GnRH neurons and their neural circuits by GS in female rats. Concerning the drug delivery route, intracerebroventricular (ICV) injection technique was employed to eliminate the unwanted actions on the extrabrain tissues which can be occurred if the testing drug is systemically administered. Adult female rats (PND 100, 210-230 g BW) were anaesthetized, treated with single dose of GS ($3.4{\mu}g$/animal), and sacrificed at 3 hrs post-injection. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). ICV infusion of GS significantly raised the transcriptional activities of enhanced at puberty1 (EAP-1, p<0.05), glutamic acid decarboxylase (GAD67, p<0.01) which are known to modulate GnRH secretion in the hypothalamus. However, GS infusion could not change the mRNA level of nitric oxide synthase 2 (NOS-2). GS administration significantly increased the mRNA levels of KiSS-1 (p<0.001), GPR54 (p<0.001), and GnRH (p<0.01) in the hypothalami, but decreased the mRNA levels of LH-$\beta$ (p<0.01) and FSH-$\beta$ (p<0.05) in the pituitaries. Taken together, the present study indicated that the acute exposure to GS could directly activate the hypothalamic GnRH modulating system, suggesting the GS's disrupting effects such as the early onset of puberty in immature female rats might be derived from premature activation of key reproduction related genes in hypothalamus-pituitary neuroendocrine circuit.

Evaluating Appropriateness of Medication Use in the Operating Rooms of a Tertiary Hospital: Based on Survey (일개 병원의 수술실 약제관련 업무 적정화 방안연구: 설문조사를 중심으로)

  • Lee, Ye Ji;Jeong, Kyeong Hye;Kim, Young Nam;Kim, Eun Young
    • Korean Journal of Clinical Pharmacy
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    • v.26 no.3
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    • pp.230-237
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    • 2016
  • Background: Since the use of opioid analgesics is frequent in operation rooms (OR), the risk of medication error is high; however the use of medication in the OR has been operating independently with the hospital pharmacy. Therefore, the assessment on management of medication use in operation and the pharmacist's role is needed. Methods: We conducted the literature review and survey from anesthesiologists, operating nurses at Chung-Ang Hospital on management of medication for operation use, awareness on need for medication management efficiency, need for satellite pharmacy in the operating room and its effect. Results: 56% of medical staffs responded that management of medication in the operating room is efficient; however, 82.6% responded that they felt the inconvenience in medication delivery to the OR when additional prescription was ordered. 51.5% also responded that extra time was required for management of narcotics and inventory/record keeping. 80% agreed that there could be lost costs due to prescription missed. Medical staffs responded improving the drug management system could increase the OR efficiency (87%), and eventually bring the increase in hospital revenue (80.4%). Those who responded that implementation of OR satellite pharmacy was needed include physicians (84.6%), nurses (63.6%), and also responded that it'd bring more profit to the hospital by increasing the efficiency in OR (60.9%). Conclusion: For efficient management of medications, implementation of OR satellite pharmacy would lead to improved drug management and increased efficiency in OR and reduced cost and improved patient care.

Improved Antitumor Efficacy of Hyaluronic Acid-Complexed Paclitaxel Nanoemulsions in Treating Non-Small Cell Lung Cancer

  • Kim, Joo-Eun;Park, Young-Joon
    • Biomolecules & Therapeutics
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    • v.25 no.4
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    • pp.411-416
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    • 2017
  • Paclitaxel (PTX) is a effectively chemotherapeutic agent which is extensively able to treat the non-small cell lung, pancreatic, breast and other cancers. But it is a practically insoluble drug with water solubility less than $1{\mu}g/mL$, which restricts its therapeutic application. To overcome the problem, hyaluronic acid-complexed paclitaxel nanoemulsions (HPNs) were prepared by ionic complexation of paclitaxel (PTX) nanoemulsions and hyaluronic acid (HA) to specifically target non-small cell lung cancer. HPNs were composed of ${\small{DL}}-{\alpha}$-tocopheryl acetate, soybean oil, polysorbate 80, ferric chloride, and HA and fabricated by high-pressure homogenization. The HPNs were $85.2{\pm}7.55nm$ in diameter and had a zeta potential of $-35.7{\pm}0.25mV$. The encapsulation efficiency was almost 100%, and the PTX content was 3.0 mg/mL. We assessed the in vivo antitumor efficacy of the HPNs by measuring changes in tumor volume and body weight in nude mice transplanted with CD44-overexpressing NCI-H460 xenografts and treated with a bolus dose of saline, $Taxol^{(R)}$, PTX nanoemulsions (PNs), or HPNs at a dose of 25 mg/kg. Suppression of cancer cell growth was higher in the PN- and HPN-treated groups than in the $Taxol^{(R)}$ group. In particular, HPN treatment dramatically inhibited tumor growth, likely because of the specific tumor-targeting affinity of HA for CD44-overexpressed cancer cells. The loss of body weight and organ weight did not vary significantly between the groups. It is suggest that HPNs should be used to effective nanocarrier system for targeting delivery of non-small cell lung cancer overexpressing CD44 and high solubilization of poorly soluble drug.

Temperature-sensitive Liposomes Modified with Poly(N-isopropylacrylamide-co-acrylamide) (Poly(N-isopropylacrylamide-co-acrylamide)로 변형된 온도민감성 리포좀)

  • Hee Dong Han;Sung Soo Kim;Ho Suk Choi;Byung Cheol Shin
    • Journal of the Korean Chemical Society
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    • v.47 no.3
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    • pp.257-264
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    • 2003
  • This study has investigated the temperature-sensitive liposomes, which release anticancer drug(doxorubicin) at the hyperthermia temperature$(~40^{\circ}C)$. The temperature-sensitive liposomes were modified with a copolymers of N-isopropylacrylamide(NIPAAm) and acrylamide(AAm), which exhibit a lower critical solution temperature (LCST) at the hyperthermia temperature. The release of doxorubicin from the modified liposomes was determined by measuring the fluorescence intensity with changing temperature and time. The release of doxorubicin from liposomes modified with poly(NIPAAm-co-AAm) copolymer was increased significantly, because poly(NIPAAm-co-AAm) could undergo the conformational transition in the narrow hyperthermia temperature region$(~40{\pm}2^{\circ}C)$. Moreover, we observed that doxorubicin released from liposomes within 5 minutes, and the size of modified liposomes was 120~170 nm. In this study, we have prepared temperature-sensitive liposomes which could be controlled by temperature. They can be applied in the field of a drug delivery system for tumor targeting by temperature control.

Glutamate Receptor Abnormalities in Schizophrenia: Implications for Innovative Treatments

  • Rubio, Maria D.;Drummond, Jana B.;Meador-Woodruff, James H.
    • Biomolecules & Therapeutics
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    • v.20 no.1
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    • pp.1-18
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    • 2012
  • Schizophrenia is a devastating psychiatric illness that afflicts 1% of the population worldwide, resulting in substantial impact to patients, their families, and health care delivery systems. For many years, schizophrenia has been felt to be associated with dysregulated dopaminergic neurotransmission as a key feature of the pathophysiology of the illness. Although numerous studies point to dopaminergic abnormalities in schizophrenia, dopamine dysfunction cannot completely account for all of the symptoms seen in schizophrenia, and dopamine-based treatments are often inadequate and can be associated with serious side effects. More recently, converging lines of evidence have suggested that there are abnormalities of glutamate transmission in schizophrenia. Glutamatergic neurotransmission involves numerous molecules that facilitate glutamate release, receptor activation, glutamate reuptake, and other synaptic activities. Evidence for glutamatergic abnormalities in schizophrenia primarily has implicated the NMDA and AMPA subtypes of the glutamate receptor. The expression of these receptors and other molecules associated with glutamate neurotransmission has been systematically studied in the brain in schizophrenia. These studies have generally revealed region- and molecule-specifi c changes in glutamate receptor transcript and protein expression in this illness. Given that glutamatergic neurotransmission has been implicated in the pathophysiology of schizophrenia, recent drug development efforts have targeted the glutamate system. Much effort to date has focused on modulation of the NMDA receptor, although more recently other glutamate receptors and transporters have been the targets of drug development. These efforts have been promising thus far, and ongoing efforts to develop additional drugs that modulate glutamatergic neurotransmission are underway that may hold the potential for novel classes of more effective treatments for this serious psychiatric illness.