scholarly journals pH-Responsive i-motif Conjugated Hyaluronic Acid/Polyethylenimine Complexes for Drug Delivery Systems

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 247 ◽  
Author(s):  
Gyeong Jin Lee ◽  
Tae-il Kim

i-motif is cytosine (C)-rich oligonucleotide (ODN) which shows pH-responsive structure change in acidic condition. Therefore, it has been utilized for the trigger of intercalated drug release, responding to environmental pH change. In this study, 2.76 molecules of i-motif binding ODNs (IBOs) were conjugated to each hyaluronic acid (HA) via amide bond linkages. Synthesis of HA-IBO conjugate (HB) was confirmed by FT-IR and agarose gel electrophoresis with Stains-All staining. After hybridization of HB with i-motif ODN (IMO), it was confirmed that doxorubicin (DOX) could be loaded in HB-IMO hybrid structure (HBIM) with 65.6% of drug loading efficiency (DLE) and 25.0% of drug loading content (DLC). At pH 5.5, prompt and significant DOX release from HBIM was observed due to the disruption of HBIM hybrid structure via i-motif formation of IMO, contrary to pH 7.4 condition. Then, HBIM was complexed with low molecular weight polyethylenimine (PEI1.8k), forming positively charged nanostructures (Z-average size: 126.0 ± 0.4 nm, zeta-potential: 16.1 ± 0.3 mV). DOX-loaded HBIM/PEI complexes displayed higher anticancer efficacy than free DOX in A549 cells, showing the potential for pH-responsive anticancer drug delivery systems.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yongtai Zhang ◽  
Qing Xia ◽  
Tong Wu ◽  
Zehui He ◽  
Yanyan Li ◽  
...  

Abstract Background A red blood cell membrane (RBCm)-derived drug delivery system allows prolonged circulation of an antitumor treatment and overcomes the issue of accelerated blood clearance induced by PEGylation. However, RBCm-derived drug delivery systems are limited by low drug-loading capacities and the lack of tumor-targeting ability. Thus, new designs of RBCm-based delivery systems are needed. Results Herein, we designed hyaluronic acid (HA)–hybridized RBCm (HA&RBCm)-coated lipid multichambered nanoparticles (HA&RBCm-LCNPs) to remedy the limitations of traditional RBCm drug delivery systems. The inner core co-assembled with phospholipid-regulated glycerol dioleate/water system in HA&RBCm-LCNPs met the required level of blood compatibility for intravenous administration. These newly designed nanocarriers had a honeycomb structure with abundant spaces that efficiently encapsulated paclitaxel and IR780 for photochemotherapy. The HA&RBCm coating allowed the nanocarriers to overcome the reticuloendothelial system barrier and enhanced the nanocarriers specificity to A549 cells with high levels of CD44. These properties enhanced the combinatorial antitumor effects of paclitaxel and IR780 associated with microtubule destruction and the mitochondrial apoptotic pathway. Conclusions The multifunctional HA&RBCm-LCNPs we designed expanded the functionality of RBCm and resulted in a vehicle for safe and efficient antitumor treatment. Graphical abstract


2019 ◽  
Vol 26 (14) ◽  
pp. 2502-2513 ◽  
Author(s):  
Md. Iqbal Hassan Khan ◽  
Xingye An ◽  
Lei Dai ◽  
Hailong Li ◽  
Avik Khan ◽  
...  

The development of innovative drug delivery systems, versatile to different drug characteristics with better effectiveness and safety, has always been in high demand. Chitosan, an aminopolysaccharide, derived from natural chitin biomass, has received much attention as one of the emerging pharmaceutical excipients and drug delivery entities. Chitosan and its derivatives can be used for direct compression tablets, as disintegrant for controlled release or for improving dissolution. Chitosan has been reported for use in drug delivery system to produce drugs with enhanced muco-adhesiveness, permeation, absorption and bioavailability. Due to filmogenic and ionic properties of chitosan and its derivative(s), drug release mechanism using microsphere technology in hydrogel formulation is particularly relevant to pharmaceutical product development. This review highlights the suitability and future of chitosan in drug delivery with special attention to drug loading and release from chitosan based hydrogels. Extensive studies on the favorable non-toxicity, biocompatibility, biodegradability, solubility and molecular weight variation have made this polymer an attractive candidate for developing novel drug delivery systems including various advanced therapeutic applications such as gene delivery, DNA based drugs, organ specific drug carrier, cancer drug carrier, etc.


2020 ◽  
Vol 26 (33) ◽  
pp. 4174-4184
Author(s):  
Marina P. Abuçafy ◽  
Bruna L. da Silva ◽  
João A. Oshiro-Junior ◽  
Eloisa B. Manaia ◽  
Bruna G. Chiari-Andréo ◽  
...  

Nanoparticles as drug delivery systems and diagnostic agents have gained much attention in recent years, especially for cancer treatment. Nanocarriers improve the therapeutic efficiency and bioavailability of antitumor drugs, besides providing preferential accumulation at the target site. Among different types of nanocarriers for drug delivery assays, metal-organic frameworks (MOFs) have attracted increasing interest in the academic community. MOFs are an emerging class of coordination polymers constructed of metal nodes or clusters and organic linkers that show the capacity to combine a porous structure with high drug loading through distinct kinds of interactions, overcoming the limitations of traditional drug carriers explored up to date. Despite the rational design and synthesis of MOFs, structural aspects and some applications of these materials like gas adsorption have already been comprehensively described in recent years; it is time to demonstrate their potential applications in biomedicine. In this context, MOFs can be used as drug delivery systems and theranostic platforms due to their ability to release drugs and accommodate imaging agents. This review describes the intrinsic characteristics of nanocarriers used in cancer therapy and highlights the latest advances in MOFs as anticancer drug delivery systems and diagnostic agents.


2020 ◽  
Vol 21 (11) ◽  
pp. 902-909
Author(s):  
Jingxin Zhang ◽  
Weiyue Shi ◽  
Gangqiang Xue ◽  
Qiang Ma ◽  
Haixin Cui ◽  
...  

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.


2019 ◽  
Vol 9 (1) ◽  
pp. 2-14
Author(s):  
Sahil Kumar ◽  
Bandna Sharma ◽  
Kiran Thakur ◽  
Tilak R. Bhardwaj ◽  
Deo N. Prasad ◽  
...  

Background: Many efforts have been explored in the last decade to treat colon cancer but nanoparticulate drug delivery systems are making a vital contribution in the improvement of drug delivery to colon cancer cells. Objective: In this review, we attempt to highlight recent advancements in the development of novel drug delivery systems of nanoparticles for the targeted drug delivery to colon. Polymers like Epithelial Cell Adhesion Molecule (EpCAM) aptamer chitosan, Hyaluronic Acid (HA), Chitosan (CS)– Carboxymethyl Starch (CMS), silsesquioxane capped mesoporous silica, Near IR (NIR) fluorescent Human Serum Albumin (HAS), poly(ethylene glycol)-conjugated hyaluronic acid etc. have been discussed by employing various anticancer drugs like doxorubicin, oxaliplatin, paclitaxel, 5-fluorouracil etc. Conclusion: These novel drug delivery systems have been determined to be more efficacious in terms of stability, sustained and targeted drug delivery, therapeutic efficacy, improved bioavailability and enhanced anticancer activity.


Author(s):  
Daniela Díaz-Zepeda ◽  
René D. Peralta-Rodríguez ◽  
Bertha Puente-Urbina ◽  
Gladis Cortez-Mazatan ◽  
H. Iván Meléndez-Ortiz

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 460
Author(s):  
Minja Mladenović ◽  
Ibrahim Morgan ◽  
Nebojša Ilić ◽  
Mohamad Saoud ◽  
Marija V. Pergal ◽  
...  

Ruthenium complexes are attracting interest in cancer treatment due to their potent cytotoxic activity. However, as their high toxicity may also affect healthy tissues, efficient and selective drug delivery systems to tumour tissues are needed. Our study focuses on the construction of such drug delivery systems for the delivery of cytotoxic Ru(II) complexes upon exposure to a weakly acidic environment of tumours. As nanocarriers, mesoporous silica nanoparticles (MSN) are utilized, whose surface is functionalized with two types of ligands, (2-thienylmethyl)hydrazine hydrochloride (H1) and (5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)hydrazine (H2), which were attached to MSN through a pH-responsive hydrazone linkage. Further coordination to ruthenium(II) center yielded two types of nanomaterials MSN-H1[Ru] and MSN-H2[Ru]. Spectrophotometric measurements of the drug release kinetics at different pH (5.0, 6.0 and 7.4) confirm the enhanced release of Ru(II) complexes at lower pH values, which is further supported by inductively coupled plasma optical emission spectrometry (ICP-OES) measurements. Furthermore, the cytotoxicity effect of the released metallotherapeutics is evaluated in vitro on metastatic B16F1 melanoma cells and enhanced cancer cell-killing efficacy is demonstrated upon exposure of the nanomaterials to weakly acidic conditions. The obtained results showcase the promising capabilities of the designed MSN nanocarriers for the pH-responsive delivery of metallotherapeutics and targeted treatment of cancer.


Author(s):  
Sunitha M Reddy ◽  
Sravani Baskarla

This article describes current strategies to enhance aqueous solubility and dissolution rate of poor soluble drugs. Most drugs in the market are lipophilic with low or poor water solubility. There are various methods to enhance solubility: co-solvency, particle size reduction, salt formation and Self Nanoemulsifying drug delivery systems, SEDDS is a novel approach to enhance solubility, dissolution rate and bioavailability of drugs. The study involves formulation and evaluation of solid self-Nano emulsifying drug delivery system (S-SNEDDS) to enhance aqueous solubility and dissolution rate. Oral route is the most convenient route for non-invasive administration. S-SNEDDS has more advantages when compared to the liquid self-emulsifying drug delivery system. Excipients were selected depends upon the drug compatibility oils, surfactants and co surfactants were selected to formulate Liquid SNEDDS these formulated liquid self-nano emulsifying drug delivery system converted into solid by the help of porous carriers, Melted binder or with the help of drying process. Conversion process of liquid to solid involves various techniques; they are spray drying; freeze drying and fluid bed coating technique; extrusion, melting granulation technique. Liquid SNEDDS has a high ability to improve dissolution and solubility of drugs but it also has disadvantages like incompatibility, decreased drug loading, shorter shelf life, ease of manufacturing and ability to deliver peptides that are prone to enzymatic hydrolysis.  


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