• Journal of Pharmaceutical Investigation
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• 제34권2호
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• pp.101-106
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• 2004

This work aims at examining the cellular uptake behavior of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles derivatized with a protein transduction domain (PTD) using HeLa cells. For this purpose, $Tat_{49-57}$ peptide derived from transcriptional activation (Tat) protein of HIV type-1 was covalently conjugated to the terminal end of PLGA. Nanoparticles were ten prepared with the $Tat_{49-57}-PLGA$ conjugates by a spontaneous phase inversion method. The prepared particles had a mean diameter of ca. 84 nm, as measured by dynamic light scattering. The interaction of the Tat-PLGA nanoparticles with cells was examined by using confocal laser scanning microscopy. It was found tat Tat-PLGA nanoparticles incubated with HeLa cells could efficiently translocate into cytoplasm, while plain PLGA nanoparticles showed negligible cellular uptake. In addition, even at $4^{\circ}C$ or in the presence of sodium azide significant cellular internalization of Tat-PLGA nanoparticles was still observed. These results indicate that a non-endocytotic translocation mechanism might be involved in the cellular uptake of Tat-PLGA nanoparticles.

• 폴리머
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• 제36권6호
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• pp.789-794
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• 2012

생체적합성 및 생분해성의 장점을 지닌 PLGA는 우수한 기계적 성질과 분해속도를 조절할 수 있는 장점을 가지고 있지만 소수성으로 인해 세포의 초기부착률이 낮고, 지지체 내부에 영양액의 공급이 원활하지 않다. 본 연구에서는 이러한 단점을 보완하고자 탈미네랄화된 골분(DBP, demineralized bone particle) 젤을 PLGA 지지체에 함침시켰다. 다양한 형태의 지지체 압축강도를 측정한 결과 PLGA/DBP 지지체가 연골과 비슷한 강도를 가지고 있었으며, 이를 바탕으로 DBP젤을 함침시킨 PLGA/DBP젤 지지체를 제작하였다. 연골세포를 파종하여 in vivo 실험을 진행하였고 조직화 정도를 확인하기 위해 H&E, Safranin-O, Alcian blue, Collagen type I 및 Collagen type II 염색을 실시하였다. 그 결과 DBP를 함침시킨 PLGA 지지체에서 GAG, Collagen type I 및 Collagen type II의 높은 발현과 조직화를 보여 연골조직으로 대체할 수 있는 가능성을 확인하였다.

• 폴리머
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• 제33권1호
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• pp.7-12
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• 2009

PLGA미립구는 주사제형과 같은 형태로 조직공학적 응용에 이용할 수 있다. 본 연구에서는 미립구 제조시 에밀젼 형성조건에 대한 영향과 미립구 표면에 세포를 부착시키는 방법에 대하여 연구하였다. BSA를 함유하는 PLGA미립구는 수중유형(O/W)과 수중유중수형(W/O/W) 용매증발법을 이용하여 제조하였다. 미립구의 초기방출효과제어와 PLGA분해의 과정에서 발생되는 지연시간을 개선시키기 위하며 알긴산나트륨을 수상에 용해시켜 사용하였다. 미립구에 부착된 세포의 형태를 전자주사현미경(SEM)을 이용하여 분석하였고 PLGA미립구에 배양된 인간디스크세포의 증식은 MTT분석을 이용하였으며 이를 통하여 PLGA미립구 표면에 세포가 부착되었음을 확인하였다. 본 연구는 BSA가 함유된 알긴산/PLGA미립구를 이용하여 조직공학적 응용이 가능한 주사제형으로서의 가능성을 제안하였다.

• 폴리머
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• 제34권4호
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• pp.333-340
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• 2010

잘토프로펜은 프로피온산 유도체인 비스테로이드성 소염진통제로서 아급성 및 만성염증에 큰 억제 효과를 가지고 있다. 지속적인 약물의 방출을 위해서 PLGA의 분자량과 보조계면활성제의 농도를 달리하여 O/W 용매 증발법에 의해 잘토프로펜이 함유된 PLGA 미립구를 제조하였다. 잘토프로펜이 함유된 PLGA 미립구의 물리화학적 성질 및 표면형태를 조사하기 위해 주사현미경, X선 회절 분석법 그리고 시차 주사 열량계를 이용하였다. PLGA 분자량과 보조계면활성제의 농도가 증가할수록 미립구의 크기도 증가한다. PLGA 분자량과 보조계면활성제의 농도 가 증가할수록 미립구의 다공성이 줄어들고, 느린 약물의 방출을 보인다. 본 연구에서는 PLGA의 분자량과 보조계 면활성제의 농도를 조절하여 약물이 함유된 미립구의 방출 계수를 제어할 수 있을 것으로 사료된다.

• Archives of Pharmacal Research
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• 제12권2호
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• pp.88-93
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• 1989

In order to obtain some informations about the effect of molecular weight on the release rate of drug from drug carrier, two types of poly-L-glutamic acid (PLGA)-cytarabine (ara-C) conjugates, PLGA-ara-C:I and PLGA-ara-C:II, were synthesized using two types of PLGA having different average molecular weight, 43,000 and 77,800, respectively. The PLGA-ara-C conjugates were synthesized by mixed anhydride method and found to be covalently linked. Both types of conjugates charged negatively at biological pH. The pH-dependent release rate of ara-C was observed in both cases, and the release rate was accelerated in basic, acidic conditions (the k values were 0.015 $day^{-1}$ at pH 7.0, 0.024 $day^{-1}$ at pH 5.0, and 0.059 $day^{-1}$ at pH 9.0 in the case of PLGA-ara-C:I) and in the presence of pretense. The time required for the release of 16.5% of ara-C from PLGA-ara-C:I were 8 hr and 144 hr in the presence and absence of protease, respectively. Although both types of conjugates showed similar drug substitution ratio, they showed different release rates. Between the two types of conjugates, PLGA-ara-C:II showed the faster release rate (0.030 vs 0.042 $day^{-1}$ in pH 7.4 phosphate buffer solution at $37^{\circ}C$) and the smaller activation energy for the release of drug (12.5 vs 7.7 Kcal/mol) than PLGA-ara-C:I. The characteristic effect of molecular weight on the release rates of PLGA-ara-C conjugates suggests that the drug release rate might be effectively controlled over a prolonged period of time by the combined use of the different types of PLGA-ara-C conjugates having different molecular weights.

• Biomolecules & Therapeutics
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• 제16권4호
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• pp.425-430
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• 2008

The objectives of this study were to prepare PLGA film onto the surface of the capsular tension ring (CTR) for controlled drug release and investigate the influence of plasticizers, the test drug and measurement conditions on flexibility of the film. Film solutions were prepared by dissolving PLGA, plasticizer (triethyl citrate, TEC or polyethylene glycol, PEG), test drug (dexamethasone) in ethyl acetate then films were prepared by spray coating and evaporation method. Then, the flexibility of PLGA film was determined by elongation test. The addition of plasticizer, PEG or TEC to PLGA copolymer caused a depression of glass transition temperature ($T_g$) and the elasticity of PLGA films increased. The addition of dexamethasone to the PLGA/TEC matrix decreased the flexibility of film. Dimensional factors of the PLGA films such as width and thickness were significantly influenced on flexibility of films and film length and elongation speed had no considerable influence on elongation of films. In this study, sufficiently flexible and stable PLGA films capable of being coated onto CTR could be prepared. This PLGA films can be used as a platform for local drug delivery.

• 폴리머
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• 제24권5호
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• pp.728-735
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• 2000

지속적인 국소 마취의 가능성을 연구하기 위하여 펜타닐이 함유된 생분해성 poly(L-lactide-glycolide) (75 : 25 락타이드와 글리콜라이드의 몰 비, PLGA) 미립구를 제조하였다. 펜타닐 베이스가 함유된 PLGA 미립구는 일반적인 O/W 용매 증발법으로 제조하였으며 미립구의 크기는 10에서 150 $\mu\textrm{m}$의 범위에 있었다. 미립구의 표면과 단면 형태를 전자현미경으로 관찰하였고 생체외 펜타닐 베이스 방출량은 HPLC로 분석하였다. 젤라틴 유화제의 사용으로 가장 낮은 다공성 단면의 형태와 가장 높은 포접율을 가질 수 있었다. 펜타닐의 방출 패턴은 유화제의 종류, PLGA의 분자량 및 농도, 초기 약물 loading양 등과 같은 제조 조건들의 영향이 미치는 것으로 관찰되었다. 생체외에서 펜타닐 베이스의 방출은 제조 조건을 조절함으로써 거의 zero-order 형태로 25일 이상으로 지속적이었다. 또한 XRD와 DSC로 펜타닐이 함유된 PLGA 미립구의 물리화학적인 성질을 조사하였다.

• KSBB Journal
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• 제18권2호
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• pp.107-110
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• 2003

스텐트 재질인 stainless steel 표면에 모델 약물인 rose bengal을 포함한 생분해성 고분자 PLGA, PHB, MCL-PHA를 코팅하여 약물방출 특성을 조사하였다. PLGA의 농도가 낮을수록, rose bengal의 농도가 높을수록, dip-coating 시간이 길수록 약물방출이 증가하였으며, PHB > PLGA > MCL-PHA의 순서로 약물이 빨리 방출되었다. 이는 생분해성 고분자의 농도 및 종류, 약물의 농도, dip-coating 시간 등을 변화시켜 약물방출을 조절할 수 있음을 나타낸다.

• 한국정밀공학회지
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• 제33권1호
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• pp.63-67
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• 2016

We present a method of fabricating poly (lactic-co-glycolic acid) (PLGA) porous microfibers using a pore template. PLGA microfibers were synthesized using a glass capillary tube in a poly-(dimethylsiloxane) (PDMS) microfluidic chip. Gelatin solution was used as a porous template to prepare pores in microfibers. Two phases of PLGA solutions in different solvents-DMSO (dimethyl sulfoxide) and DCM (dichloromethane)-were used to control the porosity and strength of the porous microfibers. The porosity of the PLGA microfibers differed depending on the ratio of flow rates in the two phases. The porous structure was formed in a spiral shape on the microfiber. The porous structure of the microfiber is expected to improve transfer of oxygen and nutrients, which is important for cell viability in tissue engineering.

• Journal of Pharmaceutical Investigation
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• 제40권4호
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• pp.251-254
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• 2010

The formation of acylated peptide impurities in poly(lactide-co-glycolide) (PLGA) formulations is one of the major challenges to the development of successful sustained-release product. Octreotide, synthetic analogue of somatostatin, has been identified to be acylated in PLGA microsphere formulations. The purpose of this study was to investigate the pH effect on the formation of acylated octreotides by PLGA. In the incubation with PLGA in 0.1 M phosphate buffer at pH 7.4, approximately 98% of octreotide adsorbed to PLGA through 14 days and 66.3% of acylated octreotides were produced after 42 days, whereas the interaction of octreotide with PLGA was significantly inhibited in the incubation at pH 4, in which the acylated octreotides were observed to be 9.2% after 42 days. In the interaction study at pH 4.1-7.4, the production of acylated octreotides was demonstrated to be dependent on environmental pH. Below pH 5.0, the acylation of octreotide was significantly inhibited. This study indicates that the pH is the major factor for the formation of acylated octreotide in PLGA formulations.