• 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.

• 한국당과학회:학술대회논문집
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• 한국당과학회 2006년도 제1회 연례학술대회
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• pp.57-57
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• 2006

• Archives of Pharmacal Research
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• 제16권4호
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• pp.312-317
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• 1993

To confirm a new evaluation tedhnique for biodegradability of biopolymer microsphers in vivo condition, magnetic microsphere sytem was adopted for tracing the microspheres injected and lodged in micr. Microsphers of poly(DL-lactic acid), poly(L-alctic acid) and poly(DL-lactide-coglycolide)(PLGA) were prepared by solvent-extraction method and their organ distribution and biodegradation in mice was examined. Magnetic microspheres lodged in mice organs were recollected from the homogenates of mice organs with a constant flow magnetic separation apparatus. Recollected microspheres were observed by scanning electron microscopy and also were assayed for their magnetite ocntent by atomic absorption spectrophotometry to evaluate the biodegradability of polymeric microspheres. This method seems to be practical and simple to estimate the biodegradability of biopolymers over the conventional methods.

• Journal of Pharmaceutical Investigation
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• 제29권4호
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• pp.315-321
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• 1999

Poly (lactide-co-glycolide) (PLGA) microspheres containing ovalbumin (OVA) as a model protein drug were prepared by double emulsification method, and various conditions such as mixing rate, volume of outer phase and isopropyl alcohol concentration in outer phase during secondary emulsification were observed to control the size of microspheres. In addition, entrapment efficiency of OVA and protein denaturation were also evaluated. As the rate of stirring was increased, the size of particles was decreased. But excessive stirring increased the particle size of microspheres. In a preparation condition of small volume of outer phase, the particle size was decreased but the entrapment efficiency was increased. Adding isopropyl alcohol to outer phase decreased the size of particles, but increased the entrapment efficiency. Microparticles should have smaller size than $10\;{\mu}m$ to be uptaked by Peyer's patch in small intestine. High speed of mixing and relatively small volume of outer phase are needed to reduce the size. In addition, appropriate amount of isopropyl alcohol in outer phase also plays an important role in size reduction of PLGA microspheres.

• 폴리머
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• 제29권1호
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• pp.69-73
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• 2005

비바이러스성 유전자 전달체의 주요 단점인 낮은 transfection 효율에 기인한 반복투여 등을 극복하기 위하여 poly (D,L-lactide-co-glycolide)를 이용하여 DNA가 봉입된 미립구를 제조하였다. pDNA 그 자체 또는 여러 비율의 키토산/pDNA 복합체를 사용하여 봉입하였고, 그 결과 44%(pDNA 그 자체), 5%(0.7:1 미토산/pDNA 복합체), 그리고 8%(1:1 키토산/pDNA 복합체)의 봉입효율을 나타내었다. 주사전자현미경(SEM)을 통해 본 표면구조에서는 미립구 제조 직후에서는 매우 매끈한 구형을 보이다가 제조 후 41일 경에는 찌그러진 다공성의 구조를 보였는데 이는 미립구 제조에 사용한 poly(D,L-lactic-co-glycolic acid)(PLGA) 고분자의 분해에 의한 것으로 생각된다. 시험관내 방출실험에서는 0.7:1 키토산/pDNA 복합체를 사용한 미립구에서 47%의 pDNA가 26일만에 방출된데 반해, pDNA 그 자체 혹은 1:1 키토산/pDNA 복합체를 사용한 미립구에서는 각각 15% 혹은 32%의 pDNA 방출을 나타내었다.

• Archives of Pharmacal Research
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• 제23권4호
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• pp.385-390
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• 2000

To demonstrate the effect of formulation conditions on the controlled release of protein from poly(lactide-co-glycolide) (PLGA) microspheres for use as a parenteral drug carrier, ovalbumin (OVA) microspheres were prepared using the W/O/W multiple emulsion solvent evaporation and extraction method. Methylene chloride or ethyl acetate was applied as an organic phase and poly(vinyl alcohol) as a secondary emulsion stabilizer. Low loading efficiencies of less than 20％ were observed and the in vitro release of OVA showed a burst effect in all batches of different microspheres, followed by a gradual release over the next 6 weeks. Formulation processes affected the size and morphology, drug content, and the controlled release of OVA from PLGA microspheres.

• 약학회지
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• 제44권4호
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• pp.293-299
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• 2000

Biodegradable microspheres made from poly-lactide-co-glycolide polymers have been considered as a new delivery system for single-dose vaccine. Purified tetanus toxoid (TT) was encapsulated in poly-lactide(PLA) and poly-lactide-co-glycolide (PLGA) microparticles using a solvent evaporation method in a multiple emulsion system (water-in oil-in water). The morphology of 77-loaded microparticles was spherical and the suface of them was smooth. The particle size was in a range of 2-10. Protein loading efficiency was 68-97.8%. PLGA (85:15) microparticle showed the highest efficiency. Protein release pattern was influenced by polymer molecular weight and composition. The release rate of PLA(Mw 100,000) microsphere was higher than any other microspheres. In consequence of the hydrolysis of PLGA(50:50) microspheres, environmental pH decreased from 7.4 to 5.0. The PLA, PLGA (75:25) and PLGA (85:15) microshperes showed no significant pH change. The antigenicity or n in microshperes was assayed by indirect sandwich ELISA using equine polyclonal tetanus antitoxin for capture antibody and human polyclonal tetanus antitoxin for primary antibody. The antigenicity of TT in PLA (Mw 100,000), PLGA(50:50, Mw 100,000) and PLGA (75:25, Mw 73,300) after 30 days incubation showed 54, 40.9 and 76.7%, respectively.

• 한국재료학회:학술대회논문집
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• 한국재료학회 2009년도 추계학술발표대회
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• pp.38.2-38.2
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• 2009

Regeration of natural tissuesor to create biological substitutes for defective or lost tissues and organs through the use of cells. In addition to cells and their porous, drugs are required to promote tissue regeneration. Therefore, the present studies were prepared using simvastatim loaded porous poly(lactide-co-glycolide) (PLGA) by double emulsion solvent evaporation water-in-oil-in-water technique (W/O/W) as drug delivery system strategies for injuring tissue. The resulting microspheres were evaluated for morphology, particle size, encapsulation efficiency, degradation of PLGA microspheres in vitro drug release and in vitro cell viability. Scanning electronic microscopic (SEM) showed that the porosities of the particles was changed by experimental conditions and cultured cells were attached well on porous microspheres surface. The X-ray diffraction (XRD) and differential scanning calometry (DSC) analysis indicate thatsimvastatim was highly dipersed in the microsphere at amorphousstate.

• Archives of Pharmacal Research
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• 제28권9호
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• pp.1092-1096
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• 2005

Huperzine A-loaded microspheres composed of poly(D,L-lactide-co-glycolide) were prepared by an O/w emulsion solvent evaporation method. The characterization of the microspheres such as drug loading, size, shape and release profile was described. The in vitro release in the initial 7 days was nearly linear with $10\%$ released per day. Thereafter drug release rate became slow gradually and about $90\%$ drug released at day 21. The in vitro release rate determined by dialysis bag method had a good correlation with the in vivo release rate. Huperzine A aqueous solution was intramuscularly injected (i.m.) at 0.4mg/kg and microspheres were intra­muscularly injected at 8.4 mg eq huperzine A/kg in rats. The maxium plasma concentration $(C_{max})$ after i.m. microspheres was only $32\%$ of that after i.m. solution. Drug in plasma could be detectd until day 14 and about $5\%$ of administered dose was residued at the injection site at day 14. The relative bioavailability of huperzine A microspheres over a period of 14 days was $94.7\%$. Inhibition of acyecholinesterase activity (AchE) in rat's cortex, hippocampus and striatum could sustain for about 14 days. In conclusion, huperzine A-loaded microspheres possessed a prolonged and complete drug release with significant inhibition of AchE for 2 weeks in rats.

• Macromolecular Research
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• 제8권2호
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• pp.80-88
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• 2000

Biodegradable microspheres were prepared with poly(L-lactide-co-glycolide) (PLGA, 75 : 25 by mole ratio) by an oil/oil solvent evaporation method for the sustained release of anti-AIDS virus agent, AZT The microspheres of relatively narrow size distribution (7.6$\pm$ 3.8 ㎛) were obtained by controlling the fabrication conditions. The shape of microspheres prepared was smooth and spherical. The efficiency of AZT loading into the PLGA microsphere was over 93% compared to that below 15% for microspheres by a conventional water/oil/water method. The effects of Preparation conditions on the morphology and in vitro AZT release pattern were investigated. in vitro release studies showed that different release pattern and release rates could be achieved by simply modifying factors in the fabrication conditions such as the type and amount of surfactant, initial amount of loaded drug, the temperature of solvent evaporation, and so on. PLCA microspheres prepared by 5% of initial drug loading, 1.0% (w/w) of surfactant concentration, and 25$\^{C}$ of solvent evaporation temperature were free from initial burst effect and a near-zero order sustained release was observed. Possible mechanisms of the near-zero order sustained release for our system have been proposed.