Asymmetric cationic lipid based non-viral vectors for an efficient nucleic acid delivery

Meka, Rakeshchandra R.; Sudhakar, Gangarajula; Marepally, Srujan; Thorat, Ketan; Rachamalla, Hari Krishnareddy; Dhayani, Ashish; Hiwale, Ankita A.; Banerjee, Rajkumar; Chaudhuri, Arabinda; Vemula, Praveen Kumar

doi:10.1039/c6ra07256a

Cited by 17 publications

(13 citation statements)

References 25 publications

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“…Consequently, to improve drug efficacy and minimize systemic toxicity, we developed a PEGylated liposomal formulation of N19 (LN19). In our study we used a novel asymmetric cationic lipid (labeled as D1) synthesized in our laboratory to make an efficient PEGylated liposome and simultaneously to increase cellular uptake by tumor cells due to the total positive charge of the liposomes . These experiments demonstrate that all of the liposomal formulations have a mean diameter of less than 100 nm (Table ), which is excellent for penetrating the blood vessels surrounding the tumor and subsequent endocytosis by the tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Design and Evaluation of PEGylated Liposomal Formulation of a Novel Multikinase Inhibitor for Enhanced Chemosensitivity and Inhibition of Metastatic Pancreatic Ductal Adenocarcinoma

Madamsetty¹,

Pal²,

Dutta³

et al. 2019

Bioconjugate Chem.

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Pancreatic ductal adenocarcinoma (PDAC) has one of the highest mortality rates among cancers. Chemotherapy is the standard first-line treatment, but only modest survival benefits are observed. With the advent of targeted therapies, epidermal growth factor receptor (EGFR) has been acknowledged as a prospective target in PDAC since it is overexpressed in up to 60% of cases. Similarly, the tyrosine-protein kinase Met (cMET) is also overexpressed in PDAC (27−60%) and is a prognostic marker for poor survival. Interestingly, EGFR and cMET share some common signaling pathways including PI3K/Akt and MAPK pathways. Small molecule inhibitors or bispecific antibodies that can target both EGFR and cMET are therefore emerging as novel options for cancer therapy. We previously developed a dual EGFR and cMET inhibitor (N19) that was able to inhibit tumor growth in nonsmall cell lung cancer models resistant to EGFR tyrosine kinase inhibitors (TKI). Here, we report the development of a novel liposomal formulation of N19 (LN19) and showed significant growth inhibition and increased sensitivity toward gemcitabine in the pancreatic adenocarcinoma orthotopic xenograft model. Taken together, our results suggest that LN19 can be valued as an effective combination therapy with conventional chemotherapy such as gemcitabine for PDAC patients.

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Section: Discussionmentioning

confidence: 99%

Design and Evaluation of PEGylated Liposomal Formulation of a Novel Multikinase Inhibitor for Enhanced Chemosensitivity and Inhibition of Metastatic Pancreatic Ductal Adenocarcinoma

Madamsetty¹,

Pal²,

Dutta³

et al. 2019

Bioconjugate Chem.

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“…Although the permanent positive charges bring cationic lipids high transfection efficiency and endosomal escape ability, they may cause severe cytotoxicity and short systemic circulation time [ 149 ]. To solve this problem, researchers proposed adjusting the charge ratio of lipid to nucleic acids [ 173 , 174 , 175 ]. However, the consequences of those attempts are not satisfying.…”

Section: Modifications Of Lipid-based Nanoparticlesmentioning

confidence: 99%

Modification of Lipid-Based Nanoparticles: An Efficient Delivery System for Nucleic Acid-Based Immunotherapy

Zhang

et al. 2022

Molecules

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Lipid-based nanoparticles (LBNPs) are biocompatible and biodegradable vesicles that are considered to be one of the most efficient drug delivery platforms. Due to the prominent advantages, such as long circulation time, slow drug release, reduced toxicity, high transfection efficiency, and endosomal escape capacity, such synthetic nanoparticles have been widely used for carrying genetic therapeutics, particularly nucleic acids that can be applied in the treatment for various diseases, including congenital diseases, cancers, virus infections, and chronic inflammations. Despite great merits and multiple successful applications, many extracellular and intracellular barriers remain and greatly impair delivery efficacy and therapeutic outcomes. As such, the current state of knowledge and pitfalls regarding the gene delivery and construction of LBNPs will be initially summarized. In order to develop a new generation of LBNPs for improved delivery profiles and therapeutic effects, the modification strategies of LBNPs will be reviewed. On the basis of these developed modifications, the performance of LBNPs as therapeutic nanoplatforms have been greatly improved and extensively applied in immunotherapies, including infectious diseases and cancers. However, the therapeutic applications of LBNPs systems are still limited due to the undesirable endosomal escape, potential aggregation, and the inefficient encapsulation of therapeutics. Herein, we will review and discuss recent advances and remaining challenges in the development of LBNPs for nucleic acid-based immunotherapy.

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“…The particle size was measured ten-times in triplicate using dynamic light scattering and applying zero-field correction. Similarly, zeta potential was measured ten-times by assessing the viscosity, 0.89 cP; dielectric constant, 79; and temperature, 25 • C, and then Smoluchowski approximation was used to derive the average value [33]. To assess the stability of liposomes, FITC-/DEX-containing liposomes were prepared and then stored at RT.…”

Section: Zatasizer-based Determination Of Liposomal Size Potential and Stabilitymentioning

confidence: 99%

Peptide-targeted Liposomal Delivery of Dexamethasone for Arthritis Therapy

Meka

Venkatesha

Acharya

et al. 2019

Nanomedicine (Lond.)

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Aim: Rheumatoid arthritis is an autoimmune disease affecting the joints. Antiarthritic drugs are given systemically, thereby exposing various healthy organs to these drugs, resulting in adverse reactions. Accordingly, there is an urgent need for targeted drug delivery methods for inflamed joints. Materials & methods: We developed a liposomal drug delivery system using a novel peptide ligand (CKPFDRALC) named ART-2, which homes to the inflamed joints when injected intravenously to rats with adjuvant-induced arthritis. Results: The ART-2-coated liposomes encapsulating an antiarthritic drug, dexamethasone (DEX), were more effective in inhibiting arthritis progression than control-DEX liposomes or free DEX, despite a comparable safety profile. Conclusion: Peptide-targeted therapy has advantages over conventional drug delivery and can be adapted for rheumatoid arthritis therapy.

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Asymmetric cationic lipid based non-viral vectors for an efficient nucleic acid delivery

Abstract: Cationic lipids have been extensively studied for their ability to complex with nucleic acids to condense and consequently deliver them into the cells.

Cited by 17 publications

References 25 publications

Design and Evaluation of PEGylated Liposomal Formulation of a Novel Multikinase Inhibitor for Enhanced Chemosensitivity and Inhibition of Metastatic Pancreatic Ductal Adenocarcinoma

Design and Evaluation of PEGylated Liposomal Formulation of a Novel Multikinase Inhibitor for Enhanced Chemosensitivity and Inhibition of Metastatic Pancreatic Ductal Adenocarcinoma

Modification of Lipid-Based Nanoparticles: An Efficient Delivery System for Nucleic Acid-Based Immunotherapy

Peptide-targeted Liposomal Delivery of Dexamethasone for Arthritis Therapy

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