Publications by authors named "Partha Laskar"

14 Publications

  • Page 1 of 1

Regression of Melanoma Following Intravenous Injection of Plumbagin Entrapped in Transferrin-Conjugated, Lipid-Polymer Hybrid Nanoparticles.

Int J Nanomedicine 2021 6;16:2615-2631. Epub 2021 Apr 6.

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK.

Background: Plumbagin, a naphthoquinone extracted from the officinal leadwort presenting promising anti-cancer properties, has its therapeutic potential limited by its inability to reach tumors in a specific way at a therapeutic concentration following systemic injection. The purpose of this study is to assess whether a novel tumor-targeted, lipid-polymer hybrid nanoparticle formulation of plumbagin would suppress the growth of B16-F10 melanoma in vitro and in vivo.

Methods: Novel lipid-polymer hybrid nanoparticles entrapping plumbagin and conjugated with transferrin, whose receptors are present in abundance on many cancer cells, have been developed. Their cellular uptake, anti-proliferative and apoptosis efficacy were assessed on various cancer cell lines in vitro. Their therapeutic efficacy was evaluated in vivo after tail vein injection to mice bearing B16-F10 melanoma tumors.

Results: The transferrin-bearing lipid-polymer hybrid nanoparticles loaded with plumbagin resulted in the disappearance of 40% of B16-F10 tumors and regression of 10% of the tumors following intravenous administration. They were well tolerated by the mice.

Conclusion: These therapeutic effects, therefore, make transferrin-bearing lipid-polymer hybrid nanoparticles entrapping plumbagin a highly promising anti-cancer nanomedicine.
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http://dx.doi.org/10.2147/IJN.S293480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039437PMC
April 2021

Nanotechnology synergized immunoengineering for cancer.

Eur J Pharm Biopharm 2021 Jun 24;163:72-101. Epub 2021 Mar 24.

Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA. Electronic address:

Novel strategies modulating the immune system yielded enhanced anticancer responses and improved cancer survival. Nevertheless, the success rate of immunotherapy in cancer treatment has been below expectation(s) due to unpredictable efficacy and off-target effects from systemic dosing of immunotherapeutic(s). As a result, there is an unmet clinical need for improving conventional immunotherapy. Nanotechnology offers several new strategies, multimodality, and multiplex biological targeting advantage to overcome many of these challenges. These efforts enable programming the pharmacodynamics, pharmacokinetics, and delivery of immunomodulatory agents/co-delivery of compounds to prime at the tumor sites for improved therapeutic benefits. This review provides an overview of the design and clinical principles of biomaterials driven nanotechnology and their potential use in personalized nanomedicines, vaccines, localized tumor modulation, and delivery strategies for cancer immunotherapy. In this review, we also summarize the latest highlights and recent advances in combinatorial therapies availed in the treatment of cold and complicated tumors. It also presents key steps and parameters implemented for clinical success. Finally, we analyse, discuss, and provide clinical perspectives on the integrated opportunities of nanotechnology and immunology to achieve synergistic and durable responses in cancer treatment.
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http://dx.doi.org/10.1016/j.ejpb.2021.03.010DOI Listing
June 2021

Octadecyl chain-bearing PEGylated poly(propyleneimine)-based dendrimersomes: physicochemical studies, redox-responsiveness, DNA condensation, cytotoxicity and gene delivery to cancer cells.

Biomater Sci 2021 Feb 6;9(4):1431-1448. Epub 2021 Jan 6.

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.

Stimuli-responsive nanocarriers have become increasingly important for nucleic acid and drug delivery in cancer therapy. Here, we report the synthesis, characterization and evaluation of disulphide-linked, octadecyl (C18 alkyl) chain-bearing PEGylated generation 3-diaminobutyric polypropylenimine dendrimer-based vesicles (or dendrimersomes) for gene delivery. The lipid-bearing PEGylated dendrimer was successfully synthesized through in situ two-step reaction. It was able to spontaneously self-assemble into stable, cationic, nanosized vesicles, with low critical aggregation concentration value, and also showed redox-responsiveness in presence of a glutathione concentration similar to that of the cytosolic reducing environment. In addition, it was able to condense more than 70% of DNA at dendrimer: DNA weight ratios of 5 : 1 and higher. This dendriplex resulted in an enhanced cellular uptake of DNA at dendrimer: DNA weight ratios of 10 : 1 and 20 : 1, by up to 16-fold and by up to 28-fold compared with naked DNA in PC-3 and DU145 prostate cancer cell lines respectively. At a dendrimer: DNA weight ratio of 20 : 1, it led to an increase in gene expression in PC-3 and DU145 cells, compared with DAB dendriplex. These octadecyl chain-bearing, PEGylated dendrimer-based vesicles are therefore promising redox-sensitive drug and gene delivery systems for potential applications in combination cancer therapy.
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http://dx.doi.org/10.1039/d0bm01441aDOI Listing
February 2021

"Tomorrow Never Dies": Recent Advances in Diagnosis, Treatment, and Prevention Modalities against Coronavirus (COVID-19) amid Controversies.

Diseases 2020 Aug 6;8(3). Epub 2020 Aug 6.

Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA.

The outbreak of novel coronavirus disease (2019-nCoV or COVID-19) is responsible for severe health emergency throughout the world. The attack of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found to be responsible for COVID-19. The World Health Organization has declared the ongoing global public health emergency as a pandemic. The whole world fights against this invincible enemy in various capacities to restore economy, lifestyle, and safe life. Enormous amount of scientific research work(s), administrative strategies, and economic measurements are in place to create a successful step against COVID-19. Furthermore, differences in opinion, facts, and implementation methods laid additional layers of complexities in this battle against survival. Thus, a timely overview of the recent, important, and overall inclusive developments against this pandemic is a pressing need for better understanding and dealing with COVID-19. In this review, we have systematically summarized the epidemiological studies, clinical features, biological properties, diagnostic methods, treatment modalities, and preventive measurements related to COVID-19.
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http://dx.doi.org/10.3390/diseases8030030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563589PMC
August 2020

Anti-Tumor Activity of Intravenously Administered Plumbagin Entrapped in Targeted Nanoparticles.

J Biomed Nanotechnol 2020 Jan;16(1):85-100

Plumbagin, a natural naphthoquinone from the officinal leadwort, has recently been shown to exert promising anti-cancer effects. However, its therapeutic use is hampered by its failure to specifically reach tumors after intravenous administration, without secondary effects on normal tissues. Its poor solubility in water and rapid elimination following administration further limit its potential use. We hypothesize that the entrapment of plumbagin within PEGylated PLGA nanoparticles conjugated with transferrin, whose receptors are overexpressed on many types of cancer cells, could lead to a selective delivery of the drug to tumors following intravenous administration and enhance its chemotherapeutic effects. The objectives of this study were therefore to prepare and characterize transferrin-conjugated, PEGylated PLGA nanoparticles entrapping plumbagin, and to assess their anti-cancer efficacy as well as in tumor-bearing mice. The intravenous administration of transferrin-conjugated PEGylated PLGA nanoparticles resulted in the complete suppression of 10% of B16-F10 tumors and regression of 30% of the tumors, with improvement of the animal survival compared to controls. The treatment was well tolerated by the animals. Transferrin-bearing PEGylated PLGA nanoparticles entrapping plumbagin are therefore highly promising therapeutic systems, able to lead to tumor regression and even suppression after intravenous administration without visible toxicity.
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http://dx.doi.org/10.1166/jbn.2020.2874DOI Listing
January 2020

Camptothecin-based dendrimersomes for gene delivery and redox-responsive drug delivery to cancer cells.

Nanoscale 2019 Nov 15;11(42):20058-20071. Epub 2019 Oct 15.

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.

Combination therapy involving chemotherapeutic drugs and genes is emerging as a promising strategy to provide a synergistic therapeutic effect, to overcome drug resistance while reducing the severe side effects associated with conventional chemotherapeutic drugs. However, the lack of nanomedicines able to simultaneously carry anti-cancer drugs and nucleic acids limits the application of this therapeutic strategy. To overcome this issue, we proposed to synthesize a pro-drug dendrimer by conjugating the PEGylated, positively charged generation 3-diaminobutyric polypropylenimine dendrimer to the anti-cancer drug camptothecin with a redox-sensitive disulphide linkage, and evaluate its efficacy to co-deliver the complexed DNA and camptothecin to cancer cells. This PEGylated pro-drug dendrimer was found to spontaneously self-assemble into cationic (∼3-5 mV) vesicles at pH 7.4, at a critical aggregation concentration of about 200 μg mL. These vesicles (dendrimersomes) became smaller (150-200 nm) with increasing dendrimer concentration and remained stable over 7 days. They were able to release about 70% of the conjugated camptothecin in presence of 50 mM glutathione (equivalent to the intracellular environment of tumor tissue). They could also condense more than 85% of the DNA at dendrimer : DNA weight ratios of 5 : 1 and higher. DNA condensation occurred instantly and was found to be stable for at least 24 h. This led to an enhanced cellular uptake of DNA (by up to 1.6-fold) and increased gene transfection (by up to 2.4-fold) in prostate cancer cells in comparison with the unmodified dendrimer. These novel dendrimersomes are therefore promising for single carrier-based combination cancer therapy.
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http://dx.doi.org/10.1039/c9nr07254cDOI Listing
November 2019

Transferrin-bearing liposomes entrapping plumbagin for targeted cancer therapy.

J Interdiscip Nanomed 2019 Jun 26;4(2):54-71. Epub 2019 Jun 26.

Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde 161 Cathedral Street Glasgow G4 0RE UK.

The therapeutic potential of plumbagin, a naphthoquinone extracted from the officinal leadwort with anticancer properties, is hampered by its failure to specifically reach tumours at a therapeutic concentration after intravenous administration, without secondary effects on normal tissues. Its use in clinic is further limited by its poor aqueous solubility, its spontaneous sublimation, and its rapid elimination . We hypothesize that the entrapment of plumbagin within liposomes grafted with transferrin, whose receptors are overexpressed on many cancer cells, could result in a selective delivery to tumours after intravenous administration. The objectives of this study were therefore to prepare and characterize transferrin-targeted liposomes entrapping plumbagin and to evaluate their therapeutic efficacy and . The entrapment of plumbagin in transferrin-bearing liposomes led to an increase in plumbagin uptake by cancer cells and improved antiproliferative efficacy and apoptosis activity in B16-F10, A431, and T98G cell lines compared with that observed with the drug solution. the intravenous injection of transferrin-bearing liposomes entrapping plumbagin led to tumour suppression for 10% of B16-F10 tumours and tumour regression for a further 10% of the tumours. By contrast, all the tumours treated with plumbagin solution or left untreated were progressive. The animals did not show any signs of toxicity. Transferrin-bearing liposomes entrapping plumbagin are therefore highly promising therapeutic systems that should be further optimized as a therapeutic tool for cancer treatment.
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http://dx.doi.org/10.1002/jin2.56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619241PMC
June 2019

Redox-sensitive, cholesterol-bearing PEGylated poly(propylene imine)-based dendrimersomes for drug and gene delivery to cancer cells.

Nanoscale 2018 Dec 29;10(48):22830-22847. Epub 2018 Nov 29.

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.

Stimuli-responsive nanocarriers have attracted increased attention as materials that can facilitate drug and gene delivery in cancer therapy. The present study reports the development of redox-sensitive dendrimersomes comprising disulfide-linked cholesterol-bearing PEGylated dendrimers, which can be used as drug and gene delivery systems. Two disulfide-linked cholesterol-bearing PEGylated generation 3 diaminobutyric polypropylenimine dendrimers have been successfully synthesized via an in situ two-step reaction. They were able to spontaneously self-assemble into stable, cationic, nanosized vesicles (or dendrimersomes) with lower critical aggregation concentration values for high-cholesterol-bearing vesicles. These dendrimersomes were able to entrap both hydrophilic and hydrophobic dyes, and they also showed a redox-responsive sustained release of the entrapped guests in the presence of a glutathione concentration similar to that of a cytosolic reducing environment. The high-cholesterol-bearing dendrimersomes were found to have a higher melting enthalpy, increased adsorption tendency on mica surface, entrapping ability for a larger amount of hydrophobic drugs, and increased resistance to redox-responsive environments in comparison with their low-cholesterol counterpart. In addition, both dendrimersomes were able to condense more than 85% of the DNA at all the tested ratios for the low-cholesterol vesicles, and at dendrimer : DNA weight ratios of 1 : 1 and higher for the high-cholesterol vesicles. These vesicles resulted in an enhanced cellular uptake of DNA, by up to 15-fold when compared with naked DNA with low-cholesterol vesicles. As a result, they increased the gene transfection on the PC-3 prostate cancer cell line, with the highest transfection being obtained with low-cholesterol vesicle complexes at a dendrimer : DNA weight ratio of 5 : 1 and high-cholesterol vesicle complexes at a dendrimer : DNA weight ratio of 10 : 1. These transfection levels were about 5-fold higher than those observed when treated with naked DNA. These cholesterol-bearing PEGylated dendrimer-based vesicles are, therefore, promising as redox-sensitive drugs and gene delivery systems for potential applications in combination cancer therapies.
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http://dx.doi.org/10.1039/c8nr08141gDOI Listing
December 2018

PEGylation of polypropylenimine dendrimers: effects on cytotoxicity, DNA condensation, gene delivery and expression in cancer cells.

Sci Rep 2018 06 20;8(1):9410. Epub 2018 Jun 20.

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, United Kingdom.

Diaminobutyric polypropylenimine (DAB) dendrimers have been shown to be highly efficient non-viral gene delivery systems for cancer therapy. However, their cytotoxicity currently limits their applications. To overcome this issue, PEGylation of DAB dendrimer, using various PEG molecular weights and dendrimer generations, has been attempted to decrease the cytotoxicity and enhance the DNA condensation, size and zeta potential, cellular uptake and transfection efficacy of these dendriplexes. Among all the PEGylated dendrimers synthesized, generation 3- and generation 4-DAB conjugated to low molecular weight PEG (2 kDa) at a dendrimer: DNA ratio of 20:1 and 10:1 resulted in an increase in gene expression on almost all tested cancer cells lines (by up to 3.2-fold compared to unmodified dendrimer in A431 cells). The highest level of β-galactosidase gene expression (10.07 × 10 ± 0.09 × 10 U/mL) was obtained following treatment of B16F10-Luc cells with G4-dendrimer PEGylated with PEG2K at a dendrimer: DNA ratio of 20:1. These delivery systems significantly decreased cytotoxicity on B16F10-Luc cells, by more than 3.4-fold compared to unmodified dendrimer. PEGylated generations 3- and 4-DAB dendrimers are therefore promising gene delivery systems for cancer therapy, combining low cytotoxicity and high transfection efficacy.
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http://dx.doi.org/10.1038/s41598-018-27400-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010408PMC
June 2018

Spontaneously formed redox- and pH-sensitive polymersomes by mPEG based cytocompatible random copolymers.

J Colloid Interface Sci 2017 Sep 12;501:22-33. Epub 2017 Apr 12.

Department of Biotechnology, Indian Institute of Technology Kharagpur, 721 302, India.

Stimuli-sensitive polymersomes are one of the important vehicles and have been extensively studied as smart drug delivery system. Polymersomes have added advantage over the micelles because of having the ability to carry not only hydrophobic but also hydrophilic guest in their aqueous core. Among various stimuli, the change of pH and redox reaction is very important for drug delivery purpose especially for anticancer drug. Therefore, in this work, two poly(ethylene glycol) methyl ether methacrylate (mPEG) containing hydrophilic random anionic copolymers, poly[(2-hydroxyethyl methacrylate-3,3'-dithiodipropanoic acid)-co-(poly(ethylene glycol) methyl ether methacrylate)], poly[(HEMA-DTDPA)-co-mPEG] with different copolymer ratios were designed and synthesized. The self-assembly behaviour of these copolymers were studied by use of various techniques, including fluorescence spectroscopy, light scattering, and electron and optical microscopy. Both the copolymers were observed to form negatively charged polymersomes spontaneously in aqueous media at pH 7. The polymersomes were shown to successfully encapsulate hydrophobic as well as hydrophilic guests. The polymersomes of both the polymers showed pH- and redox-sensitive release of encapsulated guest leading to a very good system for cytoplasmic delivery. The polymers were found to be nontoxic and hemocompatible up to a reasonably high concentration. Also the polymers did not show any denaturizing effect on the secondary structure of carrier protein, human serum albumin. It was concluded that these two dual stimuli-sensitive cytocompatible polymersomes can have potential use as drug delivery system in cancer chemotherapy.
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http://dx.doi.org/10.1016/j.jcis.2017.04.034DOI Listing
September 2017

In Vitro Drug and Gene Delivery Using Random Cationic Copolymers Forming Stable and pH-Sensitive Polymersomes.

Macromol Biosci 2017 04 23;17(4). Epub 2016 Nov 23.

Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, 721 302, India.

Stimuli-sensitive polymeric vesicles or polymersomes as self-assembled colloidal nanocarriers have received paramount importance for their integral role as delivery system for therapeutics and biotherapeutics. This work describes spontaneous polymersome formation at pH 7, as evidenced by surface tension, steady state fluorescence, dynamic light scattering, and microscopic studies, by three hydrophilic random cationic copolymers synthesized using N,N-(dimethylamino)ethyl methacrylate (DMAEM) and methoxy poly(ethylene glycol) monomethacrylate in different mole ratios. The results suggest that methoxy poly(ethylene glycol) chains constitute the bilayer membrane of the polymersomes and DMAEM projects toward water constituting the positively charged surface. The polymersomes have been observed to release their encapsulated guest at acidic pH as a result of transformation into polymeric micelles. All these highly biocompatible cationic polymers show successful gene transfection ability as nonviral vector on human cell line with different potential. Thus these polymers prove their utility as a potential delivery system for hydrophilic model drug as well as genetic material.
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http://dx.doi.org/10.1002/mabi.201600324DOI Listing
April 2017

Evaluation of zwitterionic polymersomes spontaneously formed by pH-sensitive and biocompatible PEG based random copolymers as drug delivery systems.

Colloids Surf B Biointerfaces 2016 Mar 26;139:107-16. Epub 2015 Nov 26.

Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, India.

The development of stimuli-responsive biocompatible polymersomes is important for the improvement of drug delivery systems. Herein, we report the spontaneous formation of polymersomes by three random copolymers, l-cys-graft-poly[GMA-co-mPEG300], containing different ratios of l-cysteine (Cys) and methoxy poly(ethylene glycol) (mPEG) covalently linked to the polymer backbone. Cysteine was conjugated to the polymeric backbone through metal free thiol-epoxy 'click' chemistry at final step. The copolymers, without having any typical hydrophobe in the backbone, are sufficiently surface active. The self-assembly formation of the copolymers was studied in aqueous solution by steady-state fluorescence probe technique. Spontaneous polymersomes formation, without any help of stimuli and organic solvent, above a relatively low critical aggregation concentration was confirmed by dynamic light scattering and microscopic techniques. Polymersomes were shown to be able to encapsulate not only hydrophilic dye in their aqueous core but also hydrophobic guest molecules in the bilayer membrane constituted by the mPEG chains. The polymersomes are sufficiently stable under physiological condition. These nano-sized polymersomes exhibit pH-triggered release of encapsulated guest under acidic pH. All three copolymers were found to be completely cell viable and hemocompatible up to very high concentration. Their ability to cross cell membrane was demonstrated by use of a fluorescent dye-tagged polymer. Further, these copolymers did not show any denaturising effect on the secondary structure of the human serum albumin, a transport protein in the blood. Based on the results of this study it is concluded that these spontaneously formed stable and biocompatible polymersomes can have potential use as drug delivery systems.
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http://dx.doi.org/10.1016/j.colsurfb.2015.11.042DOI Listing
March 2016

In vitro evaluation of pH-sensitive cholesterol-containing stable polymeric micelles for delivery of camptothecin.

J Colloid Interface Sci 2014 Sep 11;430:305-14. Epub 2014 Jun 11.

Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India. Electronic address:

Two novel amphiphilic statistical copolymers poly(cholesteryl acrylate-co-methoxypoly(ethylene glycol) methacrylate), poly[CHOL(y)-co-mPEG(n,x)] (for n=5, x=110 and y=15, and for n=23, x=22 and y=3) with copolymer composition (x:y) of 7:1 were designed and synthesized as a delivery system for water-insoluble anticancer agent, S-(+)-camptothecin (CPT). The polymers were synthesized using reversible addition fragmentation chain transfer (RAFT) polymerization technique and they were found to form stable polymeric micelles in water above a relatively low critical concentration. The polymeric micelles (PMs) were characterized by a number of techniques including surface tension, fluorescence, dynamic light scattering, and electron microscopy. Incorporation of CPT into the micelles and the stability of CPT-loaded micelles were studied by spectrophotometric method. Sustained release of an encapsulated fluorescent guest triggered by hydrolysis of the ester linkages in acidic pH is demonstrated. The polymers are not only hemocompatible and nontoxic in the allowed concentration range, but also they can easily permeate into the cancer cells (MCF7 and HeLa). The in vitro drug delivery assay of CPT-loaded polymeric micelles on cancer cells (HeLa) showed very good chemotherapeutic activity in the biocompatible concentration range of the copolymers.
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http://dx.doi.org/10.1016/j.jcis.2014.05.068DOI Listing
September 2014

Spontaneously formed robust steroidal vesicles: physicochemical characterization and interaction with HSA.

J Phys Chem B 2014 May 17;118(17):4561-70. Epub 2014 Apr 17.

Department of Chemistry, Indian Institute of Technology , Kharagpur - 721 302, West Bengal, India.

Self-assembled multimolecular aggregates, such as vesicles, have earned tremendous attention for their applications as model membranes and drug delivery systems. Over the past decades, enormous efforts have been dedicated to the development of stable and biocompatible vesicles that form spontaneously in aqueous solution. With the aim of preparing highly stable vesicles, we herein report the physicochemical characterization of a novel cholesterol-based chiral surfactant with l-alanine headgroup. Different techniques, such as surface tensiometry, fluorescence spectroscopy, dynamic light scattering, UV-vis spectroscopy, transmission electron microscopy, and confocal fluorescence microscopy were employed to investigate the self-assembly properties of the aforementioned single-tailed steroidal surfactant in aqueous solution. The surfactant molecule is weakly surface-active, but self-assembles to form unilamellar vesicles facilitated by the strong hydrophobic association of the cholesterol moieties, above a very low critical aggregation concentration. The vesicles are fairly stable with respect to aging, temperature, and pH of the aqueous medium. Additionally, the vesicles were found to fuse together, leading to large unilamellar vesicles. The intervesicular fusion pertaining to high stability of the vesicles could be ascribed to large hydrophobic interactions among steroidal skeletons. Furthermore, the interaction of the vesicles with human serum albumin is also investigated.
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http://dx.doi.org/10.1021/jp500323eDOI Listing
May 2014