Low molecular weight chitosan–protamine conjugate for siRNA delivery with enhanced stability and transfection efficiency

Patil, Sushilkumar; Bhatt, Priyanka; Lalani, Rohan; Amrutiya, Jitendra; Vhora, Imran; Kolte, Atul; Misra, Ambikanandan

doi:10.1039/c6ra24058e

Cited by 37 publications

(21 citation statements)

References 29 publications

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“…This huge development and evaluation of chitosan-based siRNA delivery systems has allowed the identification of several limitations. For example, their poor stability at physiological pH, due to the loss of positive charge, their weak buffering capacity, which is insufficient to ensure the endosomal escape, and their lack of cell specificity to enhance their preferential internalization in the target cells over the non-targeted ones [77]. However, the understanding of these limitations, together with the perspective of the advantages of the use of this natural polymer (e.g., biocompatibility, biodegradability, low cytotoxicity, and mucoadhesive properties) has encouraged research into alternative derivatives of chitosan that endow the delivery systems with improved or new properties [22,53].…”

Section: Chitosan For Sirna Deliverymentioning

confidence: 99%

“…The addition of specific chemical groups, such as acyl [81,83,113] and carboxymethyl groups, [99,114], into chitosan’s structure to improve its solubility in aqueous media at neutral and alkaline pH has been explored to improve siRNA delivery. Furthermore, the partial quaternization of chitosan amino groups produces trimethylchitosan (TMC), which has stable positive charges, making it soluble over a wider pH range and concurrently conferring enhanced mucoadhesive properties, although it may negatively affect its buffering capacity and increase cytotoxicity [77,84,92,104,115].…”

Section: Chitosan For Sirna Deliverymentioning

confidence: 99%

“…Some authors used low molecular weight chitosan to improve the solubility due to the reduced inter-chain interactions between short chains [77]. While others used ionic or covalent cross-linking of chitosan chains to make the resulting nanocarriers more compact and thus more resistant to polyanion competition in vivo, avoiding the siRNA displacement by other negatively charged molecules present in physiological tissues [84,85,86,104,116,117].…”

Section: Chitosan For Sirna Deliverymentioning

confidence: 99%

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Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

et al. 2019

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Natural polysaccharides are frequently used in the design of drug delivery systems due to their biocompatibility, biodegradability, and low toxicity. Moreover, they are diverse in structure, size, and charge, and their chemical functional groups can be easily modified to match the needs of the final application and mode of administration. This review focuses on polysaccharidic nanocarriers based on chitosan and hyaluronic acid for small interfering RNA (siRNA) delivery, which are highly positively and negatively charged, respectively. The key properties, strengths, and drawbacks of each polysaccharide are discussed. In addition, their use as efficient nanodelivery systems for gene silencing applications is put into context using the most recent examples from the literature. The latest advances in this field illustrate effectively how chitosan and hyaluronic acid can be modified or associated with other molecules in order to overcome their limitations to produce optimized siRNA delivery systems with promising in vitro and in vivo results.

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Section: Chitosan For Sirna Deliverymentioning

confidence: 99%

Section: Chitosan For Sirna Deliverymentioning

confidence: 99%

Section: Chitosan For Sirna Deliverymentioning

confidence: 99%

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Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

et al. 2019

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“…Four samples were analyzed: the polymer, the pure sunitinib drug, the physical mixture of sunitinib and the MPEG-PCL polymer, and the SM-MPEG-PCL formulation. Five milligrams of each sample were taken and placed inside of an aluminum pan specifically made for DSC analysis [26]. Samples were then heated to approximately 30-300 • C at a rate of 10 • C while simultaneously being under a nitrogen purge at a rate of 50 mL/min [27].…”

Section: Differential Scanning Calorimetrymentioning

confidence: 99%

Sunitinib-Loaded MPEG-PCL Micelles for the Treatment of Age-Related Macular Degeneration

et al. 2020

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Age-related macular degeneration (AMD) will be responsible for the vision impairment of more than five million late-aged adults in the next 30 years. Current treatment includes frequent intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents. However, there are methods of drug delivery that can decrease the frequency of intravitreal injections by sustaining drug release. MPEG-PCL ((methoxypoly(ethylene glycol) poly(caprolactone)) has been reported as biocompatible and biodegradable. Polymeric micelles of MPEG-PCL can be useful in efficiently delivering anti-VEGF drugs such as sunitinib to the posterior segment of the eye. In this study, the novel micellar formulation exhibited an average dynamic light scattering (DLS) particle size of 134.2 ± 2.3 nm with a zeta potential of −0.159 ± 0.07 mV. TEM imaging further confirmed the nanoscopic size of the micelles. A sunitinib malate (SM)-MPEG-PCL formulation exhibited a sustained release profile for up to seven days with an overall release percentage of 95.56 ± 2.7%. In addition to their miniscule size, the SM-MPEG-PCL formulation showed minimal cytotoxicity onto the ARPE-19 human retinal pigment epithelial cell line, reporting a percent viability of more than 88% for all concentrations tested at time intervals of 24 h. The SM-MPEG-PCL micelles also exhibited exceptional performance during an anti-VEGF ELISA that decreased the overall VEGF protein expression in the cells across a 24–72 h period. Furthermore, it can be concluded that this type of polymeric vehicle is a promising solution to symptoms caused by AMD and improving the management of those suffering from AMD.

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“…There are many methods were developed to prepared the liposomes such as detergent removal, ethanol injection, solvent removal and emulsion removal 9,17 . The characteristics like size, shape, efficiency 18 and stability of drug loading are affected to liposomes by the preparation of the methods. Initially, solvent removal or Thin lipid film hydration is the most popular method to prepare the liposomes 19 .…”

Section: Design and Development Of The Liposomesmentioning

confidence: 99%

Applications liposome in cancer drug delivery and treatment: A review

Pathak¹,

Pathak²

2019

Asian J Pharm Res Dev

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In the world the biggest challenges to cure the cancer because of the abnormal cancer cells growth in the human body which is near to uncontrollable. These cells known as the malignant cell because it produced the cancer. There are several treatments for cancer such as surgery, chemotherapy, radiation treatment etc. however such treatments have major side effects like normal cell got killed, loss of hair, the surgery person skill also in consideration and high chances of reoccurrences. Due to such side effects these treatment drugs are less popular. To reduces such side effects the liposomal based treatments are the most preferable solution. The liposomes are the phospholipid bilayer vesicles and it has high encapsulation capacity. Therefore, liposomal based treatment plays significant role in the cancer treatment with less toxicity and other many advantages. The liposomal based drug pegylated liposomal doxorubicin and daunorubicin have advanced effect in the body. Furthermore, the development of the liposomes as immunoliposomes, ligand targeted and molecular targeting. This review explores the liposomal based drug delivery system, its advance effect on the cancer cells and clinically approve liposomes formulations.

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Low molecular weight chitosan–protamine conjugate for siRNA delivery with enhanced stability and transfection efficiency

Abstract: Chitosan is among the few polymers with high biocompatibility and low cytotoxicity.

Cited by 37 publications

References 29 publications

Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

Sunitinib-Loaded MPEG-PCL Micelles for the Treatment of Age-Related Macular Degeneration

Applications liposome in cancer drug delivery and treatment: A review

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