Nitric oxide-releasing poly(lactic- <i>co</i> -glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity

Nurhasni, Hasan,Cao, Jiafu,Choi, Moonjeong,Kim, Il,Lee, Bok Luel,Jung, Yunjin,Yoo, Jin-Wook Dove Medical Press 2015 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.10 No.-

<P>Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-<I>co</I>-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-<I>co</I>-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant <I>Staphylococcus aureus</I> (MRSA) and <I>Pseudomonas aeruginosa</I> concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections.</P>

Recent advancements of nitric oxide-releasing hydrogels for wound dressing applications

Hasan Nurhasni,Jiafu Cao,Mustopa Apon Zaenal,Himawan Achmad,Umami Rifqiyah Nur,Ullah Muneeb,Wathoni Nasrul,유진욱 한국약제학회 2023 Journal of Pharmaceutical Investigation Vol.53 No.6

Background Hydrogels are three-dimensional (3D) polymer networks that can absorb significant volumes of water inside their interstices and continue connecting these interstices while maintaining an inflated network structure; this capability is due to their unusual 3D crosslinked polymer meshwork structure. Hydrogels are promising wound dressings, particularly for chronic wounds, owing to their wound-healing properties, such as flexibility, adhesion, moisture control, biocompatibility, and biodegradability. Nitric oxide (NO) is a small molecule that has been thoroughly investigated for its wound-healing activity. The diverse roles of NO in wound healing require its stable delivery to the wound site. Thus, hydrogels have been evaluated as promising scaffolds for storing and releasing NO in a controlled manner to promote and accelerate wound healing. Area covered This review sought to introduce the types of polymers used to prepare hydrogel-based wound dressings and the types of NO donors used as wound healing promoters. The preparation method of the hydrogels and their physical and chemical properties were presented herein, and recent studies on NO-releasing hydrogels for wound therapy were summarized and discussed. Selected hydrogels with unique characteristics and significant findings for wound healing were also emphasized. Expert opinion Owing to the importance of chronic wounds in healthcare, the development of functional materials that support proper and rapid wound healing is required. NO-releasing hydrogels can be employed for wound dressing applications owing to their controlled NO releasability and antibacterial and wound healing activities.

Hormone Therapy and Delivery Strategies against Cardiovascular Diseases

Acharya, Gayathri,Hasan, Nurhasni,Yoo, Jin-Wook,H. Lee, Chi Bentham Science Publishers Ltd. 2017 CURRENT PHARMACEUTICAL BIOTECHNOLOGY Vol. No.

Colon-targeted dexamethasone microcrystals with pH-sensitive chitosan/alginate/Eudragit S multilayers for the treatment of inflammatory bowel disease

Oshi, Murtada A.,Naeem, Muhammad,Bae, Junhwan,Kim, Jihyun,Lee, Juho,Hasan, Nurhasni,Kim, Wooseong,Im, Eunok,Jung, Yunjin,Yoo, Jin-Wook Elsevier 2018 Carbohydrate Polymers Vol.198 No.-

<P><B>Abstract</B></P> <P>Oral colon-targeted drug delivery has gained popularity as an effective strategy for treatment of inflammatory bowel disease (IBD). In this study, we prepared colon-targeted dexamethasone microcrystals (DXMCs) coated with multilayers of chitosan oligosaccharide (CH), alginate (AG), and finally Eudragit S 100 (ES) (ES<SUB>1</SUB>AG<SUB>4</SUB>CH<SUB>5</SUB>-DXMCs) using a layer-by-layer (LBL) coating technique. Particle size, surface charge, <I>in vitro</I> drug release, and <I>in vivo</I> anti-inflammatory activity of ES<SUB>1</SUB>AG<SUB>4</SUB>CH<SUB>5</SUB>-DXMCs were evaluated. ES<SUB>1</SUB>AG<SUB>4</SUB>CH<SUB>5</SUB>-DXMCs had an average particle size of 2.34 ± 0.19 μm and a negative surface charge of - 48 ± 9 mV. ES<SUB>1</SUB>AG<SUB>4</SUB>CH<SUB>5</SUB>-DXMCs demonstrated pH-dependent dexamethasone release, avoiding initial burst drug release in acidic pH conditions of the stomach and small intestine, and providing subsequent sustained drug release in the colonic pH. Importantly, ES<SUB>1</SUB>AG<SUB>4</SUB>CH<SUB>5</SUB>-DXMCs exhibited a significant therapeutic activity in a mouse model of colitis compared to other DXMCs. Overall, the LBL-coated DXMCs presented here could be a promising colon-targeted therapy for IBD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Dexamethasone microcrystals with colon-targeted chitosan/alginate/Eudragit S multilayers were fabricated. </LI> <LI> Unwanted burst release of dexamethasone was prevented in the upper gastrointestinal tract pH. </LI> <LI> Dexamethasone was released in a sustained manner after reaching the colonic pH. </LI> <LI> Excellent therapeutic activity was found in a mouse model of colitis. </LI> </UL> </P>

pH-triggered surface charge-reversal nanoparticles alleviate experimental murine colitis via selective accumulation in inflamed colon regions

Naeem, Muhammad,Oshi, Murtada A.,Kim, Jihyun,Lee, Juho,Cao, Jiafu,Nurhasni, Hasan,Im, Eunok,Jung, Yunjin,Yoo, Jin-Wook Elsevier 2018 Nanomedicine Vol.14 No.3

<P><B>Abstract</B></P> <P>In this study, we developed pH-triggered surface charge-reversal lipid nanoparticles (LNPs), loaded with budesonide, which could precisely deliver the drug to inflamed colon segments for the treatment of ulcerative colitis. Polyethyleneimine (PEI) was used to render LNPs cationic (PEI-LNPs), and Eudragit® S100 (ES) was coated on PEI-LNPs to obtain pH-triggered charge-reversal LNPs (ES-PEI-LNPs). ES coating avoided a burst drug release under acidic conditions mimicking the stomach and early small intestine environments and showed a sustained release in the colon. The surface charge of ES-PEI-LNPs switched from negative to positive under colonic conditions owing to pH-triggered removal of the ES coating. Bioimaging of the mouse gastrointestinal tract and confocal analysis of colon tissues revealed that ES-PEI-LNPs selectively accumulated in an inflamed colon. Furthermore, ES-PEI-LNPs mitigated experimental colitis in mice. These results suggest that the pH-triggered charge-reversal LNPs could be a promising drug carrier for ulcerative colitis therapy and other colon-targeted treatments.</P> <P><B>Graphical Abstract</B></P> <P>In this study, we developed, through intelligent design, pH-triggered surface charge-reversal lipid nanoparticles, which were shown to precisely deliver a corticosteroid drug to inflamed colon segments in an ulcerative colitis mouse model. The results of the study suggest that the pH-triggered charge-reversal lipid nanoparticles are a promising drug nanocarrier for colon-targeted therapy, including ulcerative colitis treatments.</P> <P>[DISPLAY OMISSION]</P>

산화질소가 미생물에 미치는 영향 및 이를 이용한 항균전략

최은영,노진기,핫산눌하스니,유진욱,Choi, Eun Young,Noh, Jin-Ki,Hasan, Nurhasni,Yoo, Jin-Wook 한국미생물학회 2014 미생물학회지 Vol.50 No.2

인체의 항상성 유지에 필수적인 물질로 알려진 산화질소는 인체를 침입한 미생물로부터 보호하는 면역반응에서 매우 중요한 역할을 담당하고 있다. 산화질소는 미생물에 직간접적으로 작용하여 다양한 기전으로 항균작용을 나타낸다. 항생제의 심각한 내성이 심각한 사회적 문제로 대두되면서 새로운 계열의 항생제 개발이 절실한 시점에서 항균물질로서의 산화질소에 대한 연구가 활발히 진행되고 있다. 하지만 매우 짧은 반감기와 기체분자인 산화질소를 항생제로 이용하기 위해서는 산화질소의 저장과 방출을 제어할 전략 필요하다. 본 총설에서는 산화질소의 체내에서의 생화학적 특성과 항균작용을 나타내는 다양한 기전에 대해 설명하였다. 또한 산화질소 방출을 조절하여 항균작용을 향상시키는 최근의 연구에 대해 알아보았다. Nitric oxide (NO), which has been recognized as an integral molecule in maintaining homeostasis, plays an important role in host defense against microbes. NO has diverse antimicrobial mechanisms by directly and/or indirectly interacting with microbes. Under the circumstance that there is an urgent need for a new class of antimicrobial agents due to antibiotic resistance, much effort has been made to develop a NO-based antimicrobial agent. In order to make it possible, strategies to store and release NO in a controlled manner are required because NO has a gaseous property and a very short half-life. In this review, we described NO biochemistry and its mechanisms of antimicrobial activity. In additions, we introduced various NO-releasing systems that improve NO's antimicrobial activity.