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신규 합성 당지질 함유 리포솜의 In Vitro 안정성
송충길,정순화,성하수,조선행,신병철,Song, Chung-Kil,Jung, Soon-Hwa,Seong, Ha-Soo,Cho, Sun-Hang,Shin, Byung-Cheol 대한화학회 2007 대한화학회지 Vol.51 No.1
리포솜은 수십~수백 나노미터 크기의 소포체(small vesicle)로서 약물전달에 유용한 구조체이나 체내 혈류 순환계(blood circulatory system)에서 구조적 불안정성에 의해 체내 순환시간이 짧고 세망내피계(reticuloendothelial system)에 의해 소실되어 이를 개선하기 위한 다양한 연구가 시도되고 있다. 본 연구에서는 이당류(disaccharide)로서 락토오스와 슈크로스가 1,2-디스테아로일-sn-글리세로-3-포스포에탄올아민(1,2-Distearoylsn-glycero-3-phosphoethanolamine, DSPE)과 공유결합된 새로운 당-DSPE 유도체를 합성하고 이를 리포솜의 구성성분으로 하는 리포솜을 제조함으로써 리포솜의 표면이 이당으로 수식된 리포솜을 제조하였다. 제조된 리포솜의 입자크기는 대략 100 nm였으며, 표면전하 값은 당이 수식되지 않은 대조군 리포솜이 -10 mV를 나타내었으나 당-DSPE 유도체를 함유한 리포솜의 경우 리포솜 표면에 존재하는 당의 수산화기에 의하여 표면전하의 값은 -25 mV를 나타내었다. 리포솜 내부에 모델약물인 독소루비신(doxorubicin)의 로딩효율은 약 90%를 나타내었다. 당-DSPE 유도체 함유 리포솜의 in vitro 안정성은 혈청 내에서 단백흡착량의 변화 및 리포솜의 입자크기를 관찰하여 평가하였다. 당-인지질 유도체를 함유한 리포솜은 당-인지질 유도체를 함유하지 않은 리포솜 또는 폴리에틸렌글리콜(PEG) 수식 리포솜에 비해 단백흡착의 양과 혈청 내 입자크기의 변화가 적은 것으로 관찰되었다. 이당이 결합된 DSPE와 이를 함유한 리포솜은 혈액내 안정성이 향상되어 체순환계 내에서 장시간 순환이 가능한 약물전달체로서 유용할 것이라 사료된다. Liposomes having particle size from several tens to hundreds nanometers are efficient carriers for injectable drug delivery. Enhancement of liposome stability in bloodstream has been studied because of its relatively short circulation time and fast clearance from human body by reticuloendothelial system (RES) in blood vessel. In this study, new disaccharide-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) derivatives in which lactose or sucrose as the disaccharide molecule was conjugated covalently to DSPE were synthesized. Liposomes of which surface had disaccharide molecules were prepared by incorporating the disaccharide-DSPE into liposomes as one of their lipid components. Particle size of the prepared liposomes was approximately 100 nm. The liposomes of which surface were modified with the disaccharide-DSPE showed -25 mV of zeta potential value due to the presence of hydroxyl groups on their surface, while the unmodified control liposomes showed -10 mV of zeta potential value. Loading efficiency of model drug, doxorubicin, into liposomes was about 90%. Stability of the disaccharide-modified liposomes in vitro was evaluated by monitoring the amount of protein adsorption and particle size of the liposomes in serum. Disaccharide-modified liposomes were more stable in serum than unmodified control liposomes or polyethyleneglycol (PEG)-modified liposomes due to less adsorption of serum protein and hence less increase of their particle size. The liposomes of which surface was modified with disaccharide-DSPE conjugate can be used as long-circulating carriers for drugs having high toxicity or short half-life time due to their enhanced stability in blood circulatory system.
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이중 가교제 또는 알긴산에 의해 물리적인 안정성이 향상된 히알루론산 마이크로입자의 제조
김동환(Dong-Hwan Kim),최애진(Ae-Jin Choi),박충근(Chun-Geon Park),Prabagar Balakrishnan,송충길(Chung Kil Song),심창구(Chang-Koo Shim),김대덕(Dae-Duk Kim),정석재(Suk-Jae Chung) 大韓藥學會 2011 약학회지 Vol.55 No.1
Hyaluronic acid (HA) is a natural polymer consisting of disaccharide units of D-glucuronic acid and N-acetyl- D-glucosamine. It has a great potential and success in cosmetic and biomedical applications. However, native HA is highly soluble and easily metabolized by enzymes such as hyaluronidase. Thus, various studies have been reported on modifying the physicochemical properties of HA, while maintaining its biocompatibility. For controlled drug delivery, many trials for fabricating HA microspheres were achieved under chemical reaction. The HA microspheres fabricated to improve the physical stability of HA using adipic acid dihydrazide (ADH) by cross-linking reaction has been reported earlier, however it lacks the desired physical stability and rapidly decomposes by swelling or enzymes. Therefore, we prepared double cross-linked HA microspheres (DC-HA microspheres) and alginate containing HA microspheres (AC-HA microspheres) to enhance its physicochemical properties. DC-HA microspheres were prepared using trisodium trimetaphosphate (STMP) under crosslinking reaction after ADH cross-linking reaction. AC-HA microspheres were prepared by adding alginate as a networking polymer. These microspheres were characterized by morphology, particle size, zeta potential, stability against hyaluronidase. Results showed that the DC-HA and AC-HA microspheres are more stable than that of HA microspheres.
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최민수,한희동,김태우,송충길,박은석,신병철 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.1
Depot system for local drug delivery using chitosan hydrogel has been developed to enhance the therapeutic efficacy and to prevent the severe side effect in whole body. Thus, we have prepared an injectable chitosan hydrogel containing liposomes to treat cancers clinically. Anionic liposomes incorporated to improve sustained release efficiency within chitosan hydrogel. The chitosan solution containing liposomes was designed to form a hydrogel complex at body temperature. The released behavior of doxonibicin from liposomes in chitosan hydrogel showed sustained-release caused by diffusion of doxorubicin from temperature responsive liposome into chitosan hydrogel. The chitosan hydorgel containing liposomes enhanced the therapeutic potency for the solid tumor in vivo system. Our results indicate that the liposomes in chitosan hydrogel represent a depot system for local drug delivery.
ScienceON
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