Smart chemistry-based nanosized drug delivery systems for systemic applications: A comprehensive review

Ramasamy, T.,Ruttala, H.B.,Gupta, B.,Poudel, B.K.,Choi, H.G.,Yong, C.S.,Kim, J.O. Elsevier Science Publishers 2017 Journal of controlled release Vol.258 No.-

<P>This review focuses on the smart chemistry that has been utilized in developing polymer-based drug delivery systems over the past 10 years. We provide a comprehensive overview of the different functional moieties and reducible linkages exploited in these systems, and outline their design, synthesis, and application from a therapeutic efficacy viewpoint. Furthermore, we highlight the next generation nanomedicine strategies based on this novel chemistry.</P>

Engineering of a lipid-polymer nanoarchitectural platform for highly effective combination therapy of doxorubicin and irinotecan

Ramasamy, T.,Ruttala, H. B.,Choi, J. Y.,Tran, T. H.,Kim, J. H.,Ku, S. K.,Choi, H. G.,Yong, C. S.,Kim, J. O. The Royal Society of Chemistry 2015 Chemical communications Vol.51 No.26

<P>We developed a highly stable lipid-polymer nanoarchitectural platform for effective combination therapy of doxorubicin and irinotecan in the polyelectrolyte complex nanoparticle core, followed by incorporation of the whole assembly into a lecithin bilayer. It shows great potential for the treatment of a broad range of cancers.</P> <P>Graphic Abstract</P><P>We developed a highly stable lipid-polymer nanoarchitectural platform for effective combination therapy of doxorubicin and irinotecan in the polyelectrolyte complex nanoparticle core, followed by incorporation of the whole assembly into a lecithin bilayer. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c5cc00482a'> </P>

Medicinal Chemistry : COMMUNICATION ; Engineering of a lipid-polymer nanoarchitectural platform for highly effective combination therapy of doxorubicin and irinotecan

( T. Ramasamy ),( H. B. Ruttala ),( J. Y. Choi ),( T. H. Tran ),( J. H. Kim ),( S. K. Ku ),( H. G. Choi ),( C. S. Yong ),( J. O. Kim ) 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-

We developed a highly stable lipid-polymer nanoarchitectural platform for effective combination therapy of doxorubicin and irinotecan in the polyelectrolyte complex nanoparticle core, followed by incorporation of the whole assembly into a lecithin bilayer. It shows great potential for the treatment of a broad range of cancers.

Cationic drug-based self-assembled polyelectrolyte complex micelles: Physicochemical, pharmacokinetic, and anticancer activity analysis

Ramasamy, T.,Poudel, B.K.,Ruttala, H.,Choi, J.Y.,Hieu, T.D.,Umadevi, K.,Youn, Y.S.,Choi, H.G.,Yong, C.S.,Kim, J.O. Elsevier 2016 Colloids and Surfaces B Vol.146 No.-

<P>Nanofabrication of polymeric micelles through self-assembly of an ionic block copolymer and oppositely charged small molecules has recently emerged as a promising method of formulating delivery systems. The present study therefore aimed to investigate the interaction of cationic drugs doxorubicin (DOX) and mitoxantrone (MTX) with the anionic block polymer poly(ethylene oxide)-block-poly(acrylic acid) (PEO-b-PAA) and to study the influence of these interactions on the pharmacokinetic stability and antitumor potential of the formulated micelles in clinically relevant animal models. To this end, individual DOX and MTX-loaded polyelectrolyte complex micelles (PCM) were prepared, and their physicochemical properties and pH-responsive release profiles were studied. MTX-PCM and DOX-PCM exhibited a different release profile under all pH conditions tested. MTX-PCM exhibited a monophasic release profile with no initial burst, while DOX-PCM exhibited a biphasic release. DOX-PCM showed a higher cellular uptake than that shown by MTX-PCM in A-549 cancer cells. Furthermore, DOX-PCM induced higher apoptosis of cancer cells than that induced by MTX-PCM. Importantly, both MTX-PCM and DOX-PCM showed prolonged blood circulation. MTX-PCM improved the AUC(all) of MTX 4-fold compared to a 3-fold increase by DOX-PCM for DOX. While a definite difference in blood circulation was observed between MTX-PCM and DOX-PCM in the pharmacokinetic study, both MTX-PCM and DOX-PCM suppressed tumor growth to the same level as the respective free drugs, indicating the potential of PEGylated polymeric micelles as effective delivery systems. Taken together, our results show that the nature of interactions of cationic drugs with the polyionic copolymer can have a tremendous influence on the biological performance of a delivery system. (C) 2016 Elsevier B.V. All rights reserved.</P>

Effect of DC Bias on Dielectric Properties of Nanocrystalline CuAlO2

T. Prakash,S. Ramasamy,B.S. Murty 대한금속·재료학회 2013 ELECTRONIC MATERIALS LETTERS Vol.9 No.2

Grain boundary effect on the room temperature dielectric behavior in mechanically alloyed nanocrystalline CuAlO2 has been investigated using impedance spectroscopy under the applied DC bias voltages 0 V to 4.8 V in a periodic interval of 0.2 V. Analysis of impedance data confirms the existence of double Schottky potential barrier heights (Φb) between two adjacent grains (left and right side) with grain boundary and its influences in dielectric relaxation time (τ), dielectric constant (ε') and dielectric loss (tan δ) factor. Also, clear evidence on the suppression of Φb was demonstrated in the higher applied bias voltages with the parameter τ. At equilibrium state, τ is 0.63 ms and it was reduced to 0.13 ms after the 3.2 V applied DC bias. These observed DC bias voltage effects are obeying ‘brick layer model’ and also elucidates Φb is playing a crucial role in controlling dielectric properties of nanomaterials.

Effect of Applied Bias Voltage on Grain Boundary Potential Barrier Height (Φb) in Semiconductor Nanocrystals

T. Prakash,S. Ramasamy 대한금속·재료학회 2013 ELECTRONIC MATERIALS LETTERS Vol.9 No.2

Carrier transport through electrically active grain boundaries was studied under biased condition using impedance spectroscopy in the frequency range 1 Hz to 1 MHz for a model system nanocrystalline CuSCN. Since,grain boundaries of semiconductors contain defects which often trap charge carriers and cause to form a potential barrier around them also plays a crucial role in the electrical properties of nanomaterials. The influence of bias voltage on relaxation times of grain (τg) and grain boundary (τgb) for our wet chemically prepared nanocrystalline CuSCN was estimated at a periodic increment of 0.35 V from 0 V to −4.2 V. In the static case with no applied bias voltage the grain boundary potential barrier height was found to be 0.144 eV. During each periodic increment of applied bias voltages, both the grain and grain boundary relaxation times are decreases it gives direct and unambiguous evidence on the suppression of grain boundary potential barrier height (Φb).

중소형 사업장에서 발생한 유해/비유해 고형폐기물 관리와 처분

( Rajamani S ),( Suthanthararajan R ),( Ramasami T ) 한국폐기물자원순환학회 2002 APLAS Vol.2002 No.2

유해한 범주로 분류된 가죽 분야를 포함하여, 중소형 사업장으로부터의 고형폐기물 처분에 대해서 관심이 증가되고 있다. 200개의 Effluent Treatment Plants (ETPs)와17개의 Common Effluent Treatment Plants (CETPs) 로부터 발생한 유해범주에 속한 탈수 슬러지 200,000ton 의 처분은 인도에서는 중요한 문제 중에 하나이다. 전통적으로 크롬의 50-60%만이 가죽공장 크롬염료 제혁법에 적용되어지며, 그 나머지는 폐수로 배출되어진다. 남 아시아 제혁법은 BCS(Basic Chromium Sulfate)의 형태로 200,000 ton의 크롬이 해마다 사용되며, 약 그 중 80,000 ton의 크롬염은 폐수형태로 배출되어진다. 슬러지 처분문제를 최소화 하는 관점에서, 인도와 다른 남아시아 국가에서는 적절-간단하게 운영되는 크롬 회수 및 재사용 시스템을 개발 및 추진되어졌다. 크롬의 농도가 2-3%인 농도에서 0.5%(Cr)이하로 감소함에 따라, 그 슬러지는 환경부와 산림부 (MoEF) 분류에 의하여 비유해물질로 분류 되어진다. 본 논문은 인도에서 비유해물질 뷴류인 슬러지 및 고형폐기물 뿐만이 아니라 유해범주에 속한 물질에 대해서 commercial scale의 간단하고 자립 가능한 매립처분 방법을 개발 및 채택되는 것에 다루었다. Solid waste disposal from small and medium scale industries including leather sector, which are classified under hazardous category, has become a matter of increasing concern. The disposal of 200,000 tons of dewatered hazardous category sludge generated annually from 200 Effluent Treatment Plants (ETPs) and 17 Common Effluent Treatment Plants (CETPs) is one of the serious problems in India. More than 80% of the tanneries adopt chrome-tanning practice. In traditional chrome tanning practice only 50-60% of the chromium applied is taken by the leather and the balance is discharged as waste. South Asian tanneries use annually 200,000 tons of chromium in the form of Basic Chromium Sulfate (BCS) and out of this about 80,000 tons of chromium salts are discharged as waste. With a view to minimize the disposal problem of sludge, an appropriate, simple and fully operational commercial scale chrome recovery and reuse system was developed and promoted in India and other South Asian countries. Due to the reduction in chromium concentration from the level of 2 to 3% to less than 0.5% as Cr, the sludge is classified as non-hazardous category as per the Ministry of Environment & Forests (MoEF). This paper deals with the simple and viable land disposal methods developed and adopted in India at commercial scale for hazardous category as well as for non-hazardous category sludge and solid wastes.

HAZARDOUS AND NON-HAZARDOUS CATEGORY SOLID WASTE MANAGEMENT AND DISPOSAL FROM SMALL AND MEDIUM SCALE INDUSTRIES

( Rajamani S ),( Suthanthararajan R ),( Ramasami T ) 한국폐기물자원순환학회 2002 APLAS Vol.2002 No.1

Solid waste disposal from small and medium scale industries including leather sector, which are classified under hazardous category, has become a matter of increasing concern. The disposal of 200,000 tons of dewatered hazardous category sludge generated annually from 200 Effluent Treatment Plants (ETPs) and 17 Common Effluent Treatment Plants (CETPs) is one of the serious problems in India. More than 80% of the tanneries adopt chrome-tanning practice. In traditional chrome tanning practice only 50-60% of the chromium applied is taken by the leather and the balance is discharged as waste. South Asian tanneries use annually 200,000 tons of chromium in the form of Basic Chromium Sulfate (BCS) and out of this about 80,000 tons of chromium salts are discharged as waste. With a view to minimize the disposal problem of sludge, an appropriate, simple and fully operational commercial scale chrome recovery and reuse system was developed and promoted in India and other South Asian countries. Due to the reduction in chromium concentration from the level of 2 to 3% to less than 0.5% as Cr, the sludge is classified as non-hazardous category as per the Ministry of Environment & Forests (MoEF). This paper deals with the simple and viable land disposal methods developed and adopted in India at commercial scale for hazardous category as well as for non-hazardous category sludge and solid wastes.

Multiple polysaccharide-drug complex-loaded liposomes: A unique strategy in drug loading and cancer targeting

Ruttala, H.B.,Ramasamy, T.,Gupta, B.,Choi, H.G.,Yong, C.S.,Kim, J.O. Applied Science Publishers ; Elsevier Science Ltd 2017 Carbohydrate Polymers Vol.173 No.-

In the present study, a unique strategy was developed to develop nanocarriers containing multiple therapeutics with controlled release characteristics. In this study, we demonstrated the synthesis of dextran sulfate-doxorubicin (DS-DOX) and alginate-cisplatin (AL-CIS) polymer-drug complexes to produce a transferrin ligand-conjugated liposome. The targeted nanoparticles (TL-DDAC) were nano-sized and spherical. The targeted liposome exhibited a specific receptor-mediated endocytic uptake in cancer cells. The enhanced cellular uptake of TL-DDAC resulted in a significantly better anticancer effect in resistant and sensitive breast cancer cells compared to that of the free drugs. Specifically, DOX and CIS at a molar ratio of 1:1 exhibited better therapeutic performance compared to that of other combinations. The combination of an anthracycline-based topoisomerase II inhibitor (DOX) and a platinum compound (CIS) resulted in significantly higher cell apoptosis (early and late) in both types of cancer cells. In conclusion, treatment with DS-DOX and AL-CIS based combination liposomes modified with transferrin (TL-DDAC) was an effective cancer treatment strategy. Further investigation in clinically relevant animal models is warranted to prove the therapeutic efficacy of this unique strategy.

PEGylated lipid bilayer-supported mesoporous silica nanoparticle composite for synergistic co-delivery of axitinib and celastrol in multi-targeted cancer therapy

Choi, J.Y.,Ramasamy, T.,Kim, S.Y.,Kim, J.,Ku, S.K.,Youn, Y.S.,Kim, J.R.,Jeong, J.H.,Choi, H.G.,Yong, C.S.,Kim, J.O. Elsevier Science B.V. Amsterdam 2016 ACTA BIOMATERIALIA Vol. No.

Small-molecule drug combination therapies are an attractive approach to enhancing cancer chemotherapeutic responses. Therefore, this study aimed to investigate the potential of axitinib (AXT) and celastrol (CST) in targeting angiogenesis and mitochondrial-based apoptosis in cancer. Therefore, we prepared AXT/CST-loaded combination nanoparticles (ACML) with CST loaded in the mesoporous silica nanoparticles (MSN) and AXT in PEGylated lipidic bilayers. We showed that ACML effectively inhibited angiogenesis and mitochondrial function and was efficiently internalized in SCC-7, BT-474, and SH-SY5Y cells. Furthermore, hypoxia-inducible factor (HIF)-1α expression, which increased under hypoxic conditions in all cell lines exposed to ACML, markedly decreased, which may be critical for tumor inhibition. Western blotting showed the superior anticancer effect of combination nanoparticles in different cancer cells. Compared to the cocktail (AXT/CST), ACML induced synergistic cancer cell apoptosis. The AXT/CST-based combination nanoparticle synergism might be mediated by AXT, which controls vascular endothelial growth factor receptors while CST acts on target cell mitochondria. Importantly, ACML-treated mice showed remarkably higher tumor inhibition (64%) than other groups did in tumor xenograft models. Tumor xenograft immunohistochemistry revealed elevated caspase-3 and poly (ADP-ribose) polymerase and reduced CD31 and Ki-67 expression, clearly suggesting tumor apoptosis through mitochondrial and antiangiogenic effects. Overall, our results indicate that ACML potentially inhibited cell proliferation and induced apoptosis by blocking mitochondrial function, leading to enhanced antitumor efficacy. Statement of Significance: In this research, we formulated an anticancer drug combination nanoparticle loaded with axitinib (AXT) in the lipidic bilayer of PEGylated liposomes and celastrol (CST) in mesoporous silica nanoparticles. The anticancer effects of the AXT/CST-loaded combination nanoparticle (ACML) were synergistic and superior to the other formulations and involved more efficient drug delivery to the tumor site with enhanced effects on angiogenesis and mitochondrial function. Therefore, our study demonstrated that the inhibition of cell proliferation and induction of apoptosis by ACML, which was mediated by blockade of mitochondrial function and anti-angiogenesis, led to enhanced antitumor efficacy, which may be potentially useful in the clinical treatment of cancer.