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Development of PLGA micro-and nanorods with high capacity of surface ligand conjugation for enhanced targeted delivery

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Asian Journal of Pharmaceutical Sciences 2019年第1期14卷 86-94页

作者： Jiafu Cao Jin-Seok Choi Murtada A.Oshi Juho Lee Nurhasni Hasan Jihyun Kim Jin-Wook Yoo College of Pharmacy Pusan National UniversityBusan 46241South Korea Department of Medical Management Chodang UniversityMuan-gun 58530South Korea College of Nanoscience&Nanotechnology Pusan National UniversityBusan 46241South Korea

Particle shape has been recognized as one of the key properties of nanoparticles in biomedical applications including targeted drug *** ability of shape-engineered particles depends largely on targeting ligands conjugated on the particle ***,poor capacity for surface ligand conjugation remains a problem in anisotropic nanoparticles made with biodegradable polymers such as *** this study,we prepared anisotropic PLGA nanoparticles with abundant conjugatable surface functional groups by a film stretching-based fabrication method with poly(ethylene-alt-maleic acid)(PEMA).Scanning electron microscopy images showed that microrods and nanorods were successfully fabricated by the PEMA-based film stretching *** presence of surface carboxylic acid groups was confirmed by confocal microscopy and zeta potential *** the improved film-stretching method,the amount of protein conjugated to the surface of nanorods was increased ***-conjugated,nanorods fabricated by the improved method exhibited higher binding and internalization than unmodified ***,the PEMA-based film-stretching system presented in this study would be a promising fabrication method for non-spherical biodegradable polymeric micro-and nanoparticles with high capacity of surface modifications for enhanced targeted delivery.

关键词： Particle shape PLGA nanoparticles Film-stretching method Surface modification Targeted drug delivery

Mode of delivery by an ulcerative colitis mother in a case of twins: Immunological differences in cord blood and placenta

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World Journal of Gastroenterology 2018年第42期24卷 4787-4797页

作者： Garett Dunsmore Petya Koleva Reed Taylor Sutton Lindsy Ambrosio Vivian Huang Shokrollah Elahi Department of Dentistry and Department of Medical Microbiology and Immunology University of Alberta Department of Dentistry University of Alberta Division of Gastroenterology University of Alberta Division of Gastroenterology University of TorontoMount Sinai HospitalSinai Health System

AIM To understand the effects of delivery mode on the immune cells frequency and function in cord blood and *** We evaluated immunological differences in cord blood and placental tissues for a case of twins one of which delivered vaginally while the other delivered by caesarian section(C-section). Cord blood mononuclear cells were isolated and placenta tissues were processed for cell isolation. Immune phenotyping was performed by flow cytometry methods following staining for T cells, natural killer(NK) cells, monocytes, neutrophils and CD71^+erythroid cells in both cord blood and placenta tissues. In addition, fetal calprotectin of twins was measured 12 wk after *** We found lower percentages of immune cells(e.g. T cells, monocytes and neutrophils) in the cord blood of C-section delivered compared to vaginally delivered newborn. In contrast, percentages of monocytes and neutrophils were > 2 folds higher in the placental tissues of C-section delivered newborn. More importantly, we observed lower percentages of CD71^+ erythroid cells in both cord blood and placental tissues of C-section delivered case. Lower CD71^+ erythroid cells were associated with a more pro-inflammatory milieu at the fetomaternal interface reflected by higher expression of inhibitory receptors on CD4^+ T cells, higher frequency of monocytes and neutrophils. Furthermore, type of delivery impacted the gene expression profile in CD71^+erythroid cells. Finally, we found that C-section delivered child had > 20-fold higher FCP in his fecal sample at 12 wk of *** Mode of delivery impacted immune cells profile in cord blood/placenta. In particular frequency of immunosuppressive CD71^+ erythroid cells was reduced in C-section delivered newborn.

关键词： Caesarian section Twins Vaginal delivery Immunophenotyping CD71+erythroid cells Cord blood Placental tissues

Transdermal drug delivery systems in diabetes management: A review

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Asian Journal of Pharmaceutical Sciences 2020年第1期15卷 13-25页

作者： Li Ching Ng Manish Gupta School of Pharmacy Monash University MalaysiaBandar Sunway 47500Malaysia Faculty of Pharmacy DIT UniversityDehradun 248009India

Diabetes mellitus is a chronic disease in which there is an insufficient production of insulin by the pancreas, or the insulin produced is unable to be utilized effectively by the body. Diabetes affects more than 415 million people globally and is estimated to strike about 642 million people in 2040. The WHO reported that diabetes will become the seventh biggest cause of mortality in 2030. Insulin injection and oral hypoglycemic agents remain the primary treatments in diabetes management. These often present with poor patient compliance. However, over the last decade, transdermal systems in diabetes management have gained increasing attention and emerged as a potential hope in diabetes management owing to the advantages that they offer as compared to invasive injection and oral dosage forms. This review presents the recent advances and developments in transdermal research to achieve better diabetes management. Different technologies and approaches have been explored and applied to the transdermal systems to optimize diabetes management. Studies have shown that these transdermal systems demonstrate higher bioavailability compared to oral administration due to the avoidance of first-pass hepatic metabolism and a sustained drug release pattern. Besides that, transdermal systems have the advantage of reducing dosing frequency as drugs are released at a predetermined rate and control blood glucose level over a prolonged time, contributing to better patient compliance. In summary, the transdermal system is a field worth exploring due to its significant advantages over oral route in administration of antidiabetic drugs and biosensing of blood glucose level to ensure better clinical outcomes in diabetes management.

关键词： Transdermal Diabetes Antidiabetic Insulin Drug delivery system

Film forming systems for topical and transdermal drug delivery

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Asian Journal of Pharmaceutical Sciences 2017年第6期12卷 487-497页

作者： Kashmira Kathe Harsha Kathpalia Department of Pharmaceutics Vivekanand Education Society’s College of Pharmacy Chembur

Skin is considered as an important route of administration of drugs for both local and systemic effects. The effectiveness of topical therapy depends on the physicochemical properties of the drug and adherence of the patient to the treatment regimen as well as the system’s ability to adhere to skin during the therapy so as to promote drug penetration through the skin *** formulations for topical and dermatological administration of drugs have certain limitations like poor adherence to skin, poor permeability and compromised patient *** the treatment of diseases of body tissues and wounds, the drug has to be maintained at the site of treatment for an effective period of time. Topical film forming systems are such developing drug delivery systems meant for topical application to the skin, which adhere to the body, forming a thin transparent film and provide delivery of the active ingredients to the body tissue. These are intended for skin application as emollient or protective and for local action or transdermal penetration of medicament for systemic action. The transparency is an appreciable feature of this polymeric system which greatly influences the patient *** the current discussion, the film forming systems are described as a promising choice for topical and transdermal drug delivery. Further the various types of film forming systems (sprays/solutions, gels and emulsions) along with their evaluation parameters have also been reviewed.

关键词： Film forming polymers Topical drug delivery Gelling agents

Apoptosis of A549 cells by small interfering RNA targeting survivin delivery using poly-β-amino ester/guanidinylated O-carboxymethyl chitosan nanoparticles

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Asian Journal of Pharmaceutical Sciences 2020年第1期15卷 121-128页

作者： Yue Tang Yun Liu Yuwen Xie Jing Chen Yushun Dou Department of Pharmacy China Pharmaceutical UniversityNanjing 211198China

Gene-based therapeutics has emerged as a promising approach for human cancer therapy. Among a variety of non-viral vectors, polymer vectors are particularly attractive due to their safety and multivalent groups on their surface. This study focuses on guanidinylated O-carboxymethyl chitosan(GOCMCS) along with poly-β-amino ester(PBAE) for si RNA delivery. Binding efficiency of PBAE/si RNA/GOCMCS nanoparticles were characterized by gel electrophoresis. The si RNA-loaded nanoparticles were found to be stable in the presence of RNase A, serum and BALF respectively. Fine particle fraction(FPF) which was determined by a two-stage impinger(TSI) was 57.8% ± 2.6%. The particle size and zeta potential of the nanoparticles were 153.8 ± 12.54 nm and + 12.2 ± 4.94 m V. In vitro cell transfection studies were carried out with A549 cells. The cellular uptake was significantly increased. When the cells were incubated with si Survivin-loaded nanoparticles, it could induce 26.83% ± 0.59% apoptosis of A549 cells and the gene silencing level of survivin expression in A549 cells were 30.93% ± 2.27%. The results suggested that PBAE/GOCMCS nanoparticle was a very promising gene delivery carrier.

关键词： Poly-β-amino ester Guanidinylated O-carboxymethyl chitosan Nanoparticles Gene delivery

Poly(NIPAM-co-MPS)-grafted multimodal porous silica nanoparticles as reverse thermoresponsive drug delivery system

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Asian Journal of Pharmaceutical Sciences 2017年第3期12卷 279-284页

作者： Sushilkumar A.Jadhav Valentina Brunella Dominique Scalarone Gloria Berlier Department of Chemistry and NIS Research Centre University of Torino

Hybrid drug delivery systems(DDS) have been prepared by grafting poly(NIPAM-co-MPS) chains on multimodal porous silica nanoparticles having an inner mesoporous structure and an outer thin layer of micropores. The hybrid thermoresponsive DDS were fully characterized and loaded with a model drug. The in vitro drug release tests are carried out at below and above the lower critical solution temperature(LCST) of the copolymer. The results have revealed that due to the presence of small diameter(~1.3 nm) micropores at the periphery of the particles, the collapsed globules of the thermoresponsive copolymer above its LCST hinders the complete release of the drug which resulted in a reverse thermoresponsive drug release profile by the hybrid DDS.

关键词： Porous silica nanoparticles Thermoresponsive polymer Drug delivery system Ibuprofen Drug loading Drug release profile

Preparation and characterization of β-cyclodextrin grafted N-maleoyl chitosan nanoparticles for drug delivery

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Asian Journal of Pharmaceutical Sciences 2017年第6期12卷 558-568页

作者： Xinyu Hou Wenjuan Zhang Muye He Yiben Lu Kaiyan Lou Feng Gao Shanghai Key Laboratory of Functional Materials Chemistry East China University of Science and TechnologyShanghai 200237China Department of Pharmaceutics School of PharmacyEast China University of Science and TechnologyShanghai 200237China Shanghai Key Laboratory of New Drug Design East China University of Science and TechnologyShanghai 200237China

β-cyclodextrin (CD) grafted N-maleoyl chitosan (CD-g-NMCS) with two different degrees of substitution (DS) of N-maleoyl (DS = 21.2% and 30.5%) were synthesized from maleic anhydride and chitosan bearing pendant cyclodextrin (CD-g-CS). CD-g-NMCS based nanoparticles were prepared via an ionic gelation method together with chitosan and CD-g-CS *** size and zeta potential of prepared CD-g-NMCS nanoparticles were 179.2~274.0 nm and 36.2~42.4 m V, respectively. In vitro stability test indicated that CD-g-NMCS nanoparticles were more stable in phosphate-buffered saline compared with chitosan nanoparticles. Moreover, a poorly water-soluble drug, ketoprofen (KTP), was selected as a model drug to study the obtained nanoparticle’s potentials as drug delivery carriers. The drug loading efficiency of CD-g-NMCS20 nanoparticles were 14.8% for KTP. MTT assay showed that KTP loaded CD-g-NMCS nanoparticles were safe drug carriers. Notably, in vitro drug release studies showed that KTP was released in a sustained-release manner for the nanoparticles. The pharmacokinetic of drug loaded CD-g-NMCS20 nanoparticles were evaluated in rats after intravenous administration. The results of studies revealed that, compared with free KTP, KTP loaded CD-g-NMCS20 nanoparticles exhibited a significant increase in AUC0→24h and mean residence time by 6.6-fold and 2.9-fold, respectively. Therefore, CD-g-NMCS nanoparticles could be used as a novel promising nanoparticle-based drug delivery system for sustained release of poorly water-soluble drugs. The carboxylic acid groups of the CD-g-NMCS molecule provide convenient sites for further structural modifications including introduction of tissue-or disease-specific targeting groups.

关键词： β-cyclodextrin Chitosan Nanoparticle drug delivery system Ketoprofen

Amino acid transporters: Emerging roles in drug delivery for tumor-targeting therapy

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Asian Journal of Pharmaceutical Sciences 2020年第2期15卷 192-206页

作者： Ling Zhang Chengguang Sui Wenhan Yang Qiuhua Luo Department of Biotherapy The First Affiliated Hospital of China Medical UniversityShenyang 110001China Department of Pharmacy The First Affiliated Hospital of China Medical UniversityShenyang 110001China Department of Pharmacy China Medical UniversityShenyang 110001China

Amino acid transporters,which play a vital role in transporting amino acids for the biosynthesis of mammalian cells,are highly expressed in types of *** studies have shown the feasibility of amino acid transporters as a component of tumortargeting *** this review,we focus on tumor-related amino acid transporters and their potential use in tumor-targeting ***,the expression characteristics of amino acid transporters in cancer and their relationship with tumor growth are ***,the recognition requirements are discussed,focusing on the“acidbase”properties,conformational isomerism and structural ***,recent developments in amino acid transporter-targeting drug delivery strategies are highlighted,including prodrugs and nanocarriers,with special attention to the latest findings of molecular mechanisms and targeting efficiency of transporter-mediated *** aim to offer related clues that might lead to valuable tumor-targeting strategies by the utilization of amino acid transporters.

关键词： Amino acid transporter Tumor-targeting Drug delivery Prodrug Nanocarriers

Biohybrid Micro-and Nanorobots for Intelligent Drug delivery

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Cyborg and Bionic Systems 2022年第1期2022卷 187-199页

作者： Jinhua Li Lukas Dekanovsky Bahareh Khezri Bing Wu Huaijuan Zhou Zdenek Sofer School of Medical Technology Beijing Institute of TechnologyBeijing 100081China Department of Inorganic Chemistry University of Chemistry and Technology PragueTechnicka 516628 Prague 6Czech Republic

Biohybrid mico-and nanorobots are integrated tiny machines from biological components and artificial *** can poss ess the advantages of onboard actuation,sensing,control,and implementation of multiple medical tasks such as targeted drug delivery,single-cell manipulation,and cell *** review paper is to give an overview of biohybrid micro-and nanorobots for smart drug delivery ***,a wide range of biohybrid micro-and nanorobots comprising different biological components are reviewed in ***,the applications of biohybrid mico-and nanorobots for active drug delivery are introduced to demonstrate how such biohybrid micro-and nanorobots are being exploited in the field of medicine and ***,key challenges to be overcome are discussed to pave the way for the clinical translation and application of the biohybrid micro-and nanorobots.

关键词： overcome artificial delivery