• Advances in nano research
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• 제7권4호
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• pp.241-248
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• 2019

Recent researches demonstrated well promising anticancer activities for antibiotics. Such effects would be significantly increased while nanoparticle based delivery systems were applied. In this study, the goal was aim to improve anticancer and antitoxic effects of Streptomycin by loading on special kind of dendrimer (anionic-linear-globular second generation). In the current study, Size and zeta potential as well as AFM techniques have been used to prove the fact that the loading was performed correctly. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of the drug loaded on dendrimer nanoparticle were determined and compared with both of dendrimer alone and free drug with respect to staphylococcus aureus as the test microorganism. The anticancer activity among three groups including Streptomycin, Streptomycin -G2 dendrimer, and control was measured in vitro. In vitro studies showed that G2 anionic linear-globular polyethylene-glycol-based dendrimer, which loaded on Streptomycin was able to significantly improve the treatment efficacy over clinical Streptomycin alone with respect to proliferation assay. Maximal inhibitory concentration (IC50) was calculated to be $257{\mu}g/mL$ for streptomycin alone and $55{\mu}g/mL$ for Streptomycin -G2 dendrimer. In addition, Streptomycin -G2 dendrimer conjugate prevented the growth of MCF-7 cancerous cells in addition to enhance the number of apoptotic and necrotic cells as demonstrated by an annexin V-fluorescein isothiocyanate assay. Streptomycin -G2 dendrimer conjugate was able to increase Bcl-2/Bax ratio in a large scale compared with the control group and Streptomycin alone. Based on results a new drug formulation based nano-particulate was improved against S. aureus with sustained release and enhanced antibacterial activity as well as anticancer activity shown for functional cancer treatment with low side effects.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.49-54
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• 2014

Background: Hydrogels are a class of polymers that can absorb water or biological fluids and swell to several times their dry volume, dependent on changes in the external environment. In recent years, hydrogels and hydrogel nanocomposites have found a variety of biomedical applications, including drug delivery and cancer treatment. The incorporation of nanoparticulates into a hydrogel matrix can result in unique material characteristics such as enhanced mechanical properties, swelling response, and capability of remote controlled actuation. Materials and Methods: In this work, synthesis of hydrogel nanocomposites containing magnetic nanoparticles are studied. At first, magnetic nanoparticles ($Fe_3O_4$) with an average size 10 nm were prepared. At second approach, thermo and pH-sensitive poly (N-isopropylacrylamide -co-methacrylic acid-co-vinyl pyrrolidone) (NIPAAm-MAA-VP) were prepared. Swelling behavior of co-polymer was studied in buffer solutions with different pH values (pH=5.8, pH=7.4) at $37^{\circ}C$. Magnetic iron oxide nanoparticles ($Fe_3O_4$) and doxorubicin were incorporated into copolymer and drug loading was studied. The release of drug, carried out at different pH and temperatures. Finally, chemical composition, magnetic properties and morphology of doxorubicin-loaded magnetic hydrogel nanocomposites were analyzed by FT- IR, vibrating sample magnetometry (VSM), scanning electron microscopy (SEM). Results: The results indicated that drug loading efficiency was increased by increasing the drug ratio to polymer. Doxorubicin was released more at $40^{\circ}C$ and in acidic pH compared to that $37^{\circ}C$ and basic pH. Conclusions: This study suggested that the poly (NIPAAm-MAA-VP) magnetic hydrogel nanocomposite could be an effective carrier for targeting drug delivery systems of anti-cancer drugs due to its temperature sensitive properties.

• Journal of Pharmaceutical Investigation
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• 제31권4호
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• pp.241-256
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• 2001

Alginate microspheres, containing fluorescein isothiocyanate-bovine serum albumin (FITC-BSA) or green fluorescent protein (GFP) were prepared and used as a model drug to develop the oral vaccine delivery system. The alginate microspheres were coated with poly-L-lysine or chitosan. Two methods, w/o-emulsion and spray, were used to prepare alginate microspheres. To optimize preparation conditions, effects of several factors on the particle size and particle morphology of microsphere, and loading efficiency of model antigen were investigated. In both preparation methods, the particle size and the loading efficiency were enhanced when the concentration of sodium alginate increased. In the w/o-emulsion preparation method, as the concentration of Span 80 was increased from 0.5% to 2%, the particle size was decreased, but the loading efficiency was increased. The higher the emulsification speed was, the smaller the particle size and loading efficiency were. The concentration of calcium chloride did not show any effect on the particle size and loading efficiency. In the spray preparation method, the particle size was increased as the nozzle pressure $(from\;1\;kgf/m^2\;to\;3\;kgf/m^2)$ and spray rate was raised. Increasing calcium chloride concentration (<7%) decreased the particle size, in contrast to no effect of calcium chloride concentration on the w/o-emulsion preparation method. Alginate microspheres prepared by two methods were different in the particle size and loading efficiency, the particle size of microspheres prepared by the spray method was about $2-6\;{\mu}m$, larger than that prepared by the w/o emulsion method $(about\;2{\mu}m)$, and the loading efficiency was also higher with spray method. Furthermore, drying process for the microspheres prepared by the spray was simpler and easier, compared with the w/o emulsion preparation. Therefore, the spray method was chosen to prepare alginate microspheres for further experiments. Release pattern of FITC-BSA in alginate microspheres was evaluated in simulated intestinal fluid and PBS (phosphate buffered saline). Dissolution rate of FITC-BSA from alginate/chitosan microsphere was lower than that from alginate microsphere and alginate/poly-L-lysine microsphere. By confocal laser scanning microscope, it was revealed that alginate/FITC-poly-L-lysine microspheres were present in close apposition epithelium of the Peyer's patches of rabbits following inoculation into lumen of intestine, which proved that microspheres could be taken up by Peyer's patch. In conclusion, it is suggested that alginate microsphere prepared by spray method, showing a particle size of & $10\;{\mu}m$ and a high loading efficiency, can be used as a model drug for the development of oral vaccine delivery system.

• Archives of Pharmacal Research
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• 제20권4호
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• pp.324-329
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• 1997

AB-type amphiphilic copolymers (abbreviated as LE) composed of poly (L-leucine) (PLL) as the A component and poly (ethylene oxide) (PEO) as the B component were synthesized by the ring-opening polymerization of L-leucine N-carboxy-anhydride initiated by methoxy polyoxyethylene amine $(Me-PEO-NH_2)$ and characterized. Core-shell type nanoparticles were prepared by the diafiltration method. Particle size distribution obtained by dynamic light scattering was dependent on PLL composition and the size for LE-1, LE-2 and LE-3 was $369.6{\pm}267$, $523.4{\pm}410$ and $561.2{\pm}364 nm$, respectively. Shapes of the nanoparticies observed by transmission electron microscope (TEM) were almostly spherical. The critical micelle concentration (CMC) of the nanoparticles determined by a fluorescence probe technique was dependent on the composition of hydrophobic PLL, and the CMC for LE-1, LE-2 and LE-3 was $2.0{\times}10^{-6},1.7{\times}10^{-6}$ and $1.5{\times}10^{-6}(mol/l) $, respectively. Clonazepam release from core-shell type nanoparticles in vitro was dependent on PLL composition and drug loading content.

• 한국재료학회지
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• 제31권6호
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• pp.367-374
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• 2021

This paper presents the characteristics of gentamicin-loaded into cetyl trimethyl ammonium intercalated montmorillonite (GtM/CTMA/Mt) as a hybrid composite for a slow-released antibacterial delivery systems. The work describes the successful immobilization of gentamicin into the interlayers of surfactant-modified montmorillonite. Physicochemical characterization of the material is carried out by means of X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. The kinetics of the gentamicin release is investigated by in vitro study and analyzed based on UV-Vis spectrometry. In addition, antibacterial study is performed towards Klebsiella pneumoniae Staphylococcus aureus, Escherichia coli, and Streptococcus pyogenes. The results show that the gentamicin loading into CTMA/Mt increases the effectiveness of the antibacterial activity, as shown by the higher inhibition zone for all tested bacteria, compared to gentamicin as a positive control. The kinetics study suggests that the gentamicin release obeys the modified Korsmeyer-Peppas model. The physicochemical study and activity test demonstrate the feasibility of the GtM/CTMA/Mt for practical applications.

• 폴리머
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• 제32권5호
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• pp.421-426
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• 2008

pH감응형 P(MAA-co-EGMA) 수화젤을 분산 광중합을 이용하여 마이크로 크기의 미세입자로 합성하고 화장품 제형으로서의 응용 가능성을 평가하기 위하여 모델 탑재물질인 Rh-B와 화장품 분야에서 기능성 물질로 사용되는 ascorbic acid, adenosine, EGCG, arbutin을 이용하여 탑재 및 방출 거동을 조사하였다. Rh-B 탑재의 경우, pH 6.5인 수용액에서 이온화에 의한 P(MAA-co-EGMA) 수화젤의 음전하와 Rh-B의 양전하 사이의 정전기적 인력으로 인하여 가장 높은 탑재효율을 나타내었다. 그러나 화장품 기능성 물질들의 경우, pH 6.5 수용액에서 이온화된 P(MAA-co-EGMA) 수화젤의 음전하와 기능성 물질들이 나타내는 음전하 사이의 정전기적 반발력 때문에 상대적으로 낮은 탑재효율을 나타내었다. Rh-B를 사용한 방출실험 결과, p(MAA-co-EGMA) 수화젤 미세입자는 높은 pH에서는 다량의 Rh-B를 그리고 낮은 pH에서는 소량의 Rh-B를 방출하는 pH 감응성 방출거동을 나타내었다.

• 폴리머
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• 제27권1호
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• pp.9-16
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• 2003

골다공증 치료제 이프리플라본 (IP)은 조골세포의 분화와 증식을 자극하고 에스트로겐의 존재로 칼시토닌 분비를 강화한다. 조절 가능한 생분해성과 생체적합성으로 인하여 락타이드-글라이콜라이드 공중합체 (PLGA)는 약물방출조절을 연구하는데 가장 적합한 고분자중의 하나이다. 본 연구에서 IP가 함유된 PLGA 미립구는 일반적인 O/W 용매 증발법으로 제조하였으며, 미립구의 크기는 5~200 $mu extrm{m}$의 범위에 있었다. 미립구의 형태는 SEM으로 관찰하였고, 생체외 방출실험에서 IP 방출량은 HPLC로 분석 하였다. 젤라틴 및 PVA등의 유화제 사용으로 가장 높은 약물 포접율을 얻을 수 있었다. 미립구의 형태, 크기 및 약물 방출 패턴은 PLGA의 분자량 (8, 20, 33 및 90 kg/mol), 고분자용액의 농도 (2.5, 5, 10 및 20%), 유화제의 종류 (PVA, gelatin 및 Tween 80), 초기 약물 함유량 (5, 10, 20 및 30%) 및 교반속도 (250, 500 및 1000 rpm) 등과 같은 여러 제조 변수들에 의하여 조절할 수 있음을 알 수 있었다. 생체외 방출실험에서 IP 방출은 제조조건을 조절함으로써 거의 영차방출 형태로 30일 이상으로 지속적이었다 또한, XRD와 DSC로 IP 함유 PLGA 미립구의 물리화학적인 성질을 조사하여 방출메카니즘을 고찰하였다.

• 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.

• 폴리머
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• 제33권4호
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• pp.389-395
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• 2009

저분자량수용성 키토산(LMWSE)을 소수성 항진균제 전달체로 응용하기 위하여, 데옥시콜릭산(deoxycholic acid, DA)을 이용하여 LMWSE를 화학적으로 개질하였다. DA가 결합된 LMWSC 나노입자(WSEDA)의 특성은 동적 광산란기, 투과전자현미경을 이용하여 그 특성을 분석하였다. 제조되어진 나노입자의 크기는 $250{\sim}350\;nm$로 DA의 치환도가 증가함에 따라 입자의 크기가 증가하였다. 항진균제인 이트라코나졸(itraconazole)이 봉입된 WSEDA 나노입자(WSEDA-ITCN)는 소수성 상호작용을 이용한 용매 증발법으로 제조하였다. UV 분광광도계를 이용하여 약물의 함량 및 담지 효율을 측정한 결과 약물의 담지 효율은 $61{\sim}68%$로 우수한 담지 효율을 보였다. 약물방출 거동에서 이트라코나졸이 봉입된 나노파티클의 DA의 함량이 많아질수록 약물이 천천히 방출되었다. 이상의 결과로부터 본 연구에서 제조한 DA가 결합된 저분자량 수용성 키토산 나노파티클이 항진균제 전달체로서 매우 높은 응용 가능성을 나타내고 있음을 확인하였다.

• Biomaterials and Biomechanics in Bioengineering
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• 제2권3호
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• pp.159-172
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• 2015

Treatment of polymicrobial infected musculoskeletal defects continues to be a challenge in orthopaedics. This research investigated single and dual-delivery of two antibiotics, vancomycin and amikacin, targeting different classes of microorganism from a biodegradable calcium sulfate-chitosan-nHA microsphere composite scaffold. The addition of chitosan-nHA was included to provide additional structure for cellular attachment and as a secondary drug-loading device. All scaffolds exhibited an initial burst of antibiotics, but groups containing chitosan reduced the burst for amikacin at 1hr by 50%, and vancomycin by 14-25% over the first 2 days. Extended elution was present in groups containing chitosan; amikacin was above MIC ($2-4{\mu}g/mL$, Pseudomonas aeruginosa) for 7-42 days and vancomycin was above MIC ($0.5-1{\mu}g/mL$ Staphylococcus aureus) for 42 days. The antibiotic activity of the eluates was tested against S. aureus and P. aeruginosa. The elution from the dual-loaded scaffold was most effective against S. aureus (bacteriostatic 34 days and bactericidal 27 days), compared to vancomycin-loaded scaffolds (bacteriostatic and bactericidal 14 days). The dual- and amikacin-loaded scaffolds were effective against P. aeruginosa, but eluates exhibited very short antibacterial properties; only 24 hours bacteriostatic and 1-5 hours bactericidal activity. For all groups, vancomycin recovery was near 100% whereas the amikacin recovery was 41%. In conclusion, in the presence of chitosan-nHA microspheres, the dual-antibiotic loaded scaffold was able to sustain an extended vancomycin elution longer than individually loaded scaffolds. The composite scaffold shows promise as a dual-drug delivery system for infected orthopaedic wounds and overcomes some deficits of other dual-delivery systems by extending the antibiotic release.