5-Fu inclusion complex capped gold nanoparticles for breast cancer therapy
- Lakkakula, Jaya R, Krause, Rui W M, Divakaran, Deepika, Barage, Sagar, Srivastava, Rohit
- Authors: Lakkakula, Jaya R , Krause, Rui W M , Divakaran, Deepika , Barage, Sagar , Srivastava, Rohit
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/191713 , vital:45150 , xlink:href="https://doi.org/10.1016/j.molliq.2021.117262"
- Description: We have attempted to prolong the circulation time and increase the solubility of 5-Fluorouracil by complexing it with cyclodextrin and then further conjugating onto the gold nanoparticle to form 5Fu ICAu. The 1H NMR and molecular docking studies suggested that 5-Fu was included within the 2HP-β-CD cavity and H-5 proton probably serves as the binding site for stabilization of the inclusion complex. The 5Fu-ICAu showed higher cell inhibition rate when studied on MDA-MB-231 and MCF-7 breast cancer cell lines due to the enhanced permeability and retention (EPR) effect by allowing the selective accumulation of nanoparticles at tumor site. This unique system can serve as a novel nanocarrier for delivery of hydrophobic drugs.
- Full Text:
- Authors: Lakkakula, Jaya R , Krause, Rui W M , Divakaran, Deepika , Barage, Sagar , Srivastava, Rohit
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/191713 , vital:45150 , xlink:href="https://doi.org/10.1016/j.molliq.2021.117262"
- Description: We have attempted to prolong the circulation time and increase the solubility of 5-Fluorouracil by complexing it with cyclodextrin and then further conjugating onto the gold nanoparticle to form 5Fu ICAu. The 1H NMR and molecular docking studies suggested that 5-Fu was included within the 2HP-β-CD cavity and H-5 proton probably serves as the binding site for stabilization of the inclusion complex. The 5Fu-ICAu showed higher cell inhibition rate when studied on MDA-MB-231 and MCF-7 breast cancer cell lines due to the enhanced permeability and retention (EPR) effect by allowing the selective accumulation of nanoparticles at tumor site. This unique system can serve as a novel nanocarrier for delivery of hydrophobic drugs.
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Anti-malarial synergy of secondary metabolites from Morinda lucida Benth.
- Lakkakula, Jaya R, Matshaya, Thabo, Krause, Rui W M
- Authors: Lakkakula, Jaya R , Matshaya, Thabo , Krause, Rui W M
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125609 , vital:35800 , https://doi.org/10.1016/j.msec.2016.08.073
- Description: Ethnopharmacological relevance The roots, stem and leaves of Morinda lucida are used in some African countries as treatment against different types of fevers including yellow fever, malaria, trypanosomiasis and feverish conditions during child birth. Aim of the study To determine the in vitro cell toxicity and anti-malarial activity of the extracts of stem bark of M. lucida and to identify the secondary metabolites in the extract that may be responsible for this activity. Materials and methods The cell toxicity studies of crude extract [dichloromethane (DCM): Methanol (MeOH) in a ratio of1:1 (v/v)] as well as compounds isolated from the same extract were carried out using human cervix adenocarcinoma cells (HeLa cells); while the anti-malarial activities of the same samples were performed against Plasmodium falciparum strain 3D7 using the parasite lactate dehydrogenase (pLDH) assay. The isolation of the active compounds was carried out using chromatographic techniques (column and thin layer chromatography) where as mass spectrometry (MS), Fourier transform infrared spectroscopy (FTIR) as well as 1D- and 2D- nuclear magnetic resonance (NMR) analyses were employed in the characterisation and identification of the isolated secondary metabolites. Results The pLDH and cell toxicity assays for the crude extract and the fractions of M. lucida indicated that some fractions reduced the malaria parasite viability by approximately 50% at 100 μg/mL and they were not significantly cytotoxic. An IC50 done on the crude extract gave a value of 25 μg/mL. The % cell viability for the crude extract in cell toxicity assay remained at 100%. Seven chemical constituents i.e. asperuloside (1), asperulosidic acid (2), stigmasterol (3a), β-sitosterol (3b), cycloartenol (3c), campesterol (3d) and 5,15-O-dimethylmorindol (4) were isolated from the DCM-MeOH extract of stem bark. The isolated compounds tested were not that active by themselves individually at 20 μM but their activities were increased when the isolated compounds were combined. As seen when compounds 2, 3 and 4 (% viability: 93, 123 and 101 respectively) were combined yielding an IC50 value of 17 μM. Furthermore, this is the first report of compounds 1, 2, 3c, 3d and 4 isolated from M. lucida. Conclusion The crude extract completely suppressed the growth of P. falciparum. This indicates that the crude extract contains many compounds that might be acting in synergy. The observed activity of the crude extract and the samples containing a mixture of different compounds support the traditional use of M. lucida for the treatment of malaria.
- Full Text:
- Authors: Lakkakula, Jaya R , Matshaya, Thabo , Krause, Rui W M
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125609 , vital:35800 , https://doi.org/10.1016/j.msec.2016.08.073
- Description: Ethnopharmacological relevance The roots, stem and leaves of Morinda lucida are used in some African countries as treatment against different types of fevers including yellow fever, malaria, trypanosomiasis and feverish conditions during child birth. Aim of the study To determine the in vitro cell toxicity and anti-malarial activity of the extracts of stem bark of M. lucida and to identify the secondary metabolites in the extract that may be responsible for this activity. Materials and methods The cell toxicity studies of crude extract [dichloromethane (DCM): Methanol (MeOH) in a ratio of1:1 (v/v)] as well as compounds isolated from the same extract were carried out using human cervix adenocarcinoma cells (HeLa cells); while the anti-malarial activities of the same samples were performed against Plasmodium falciparum strain 3D7 using the parasite lactate dehydrogenase (pLDH) assay. The isolation of the active compounds was carried out using chromatographic techniques (column and thin layer chromatography) where as mass spectrometry (MS), Fourier transform infrared spectroscopy (FTIR) as well as 1D- and 2D- nuclear magnetic resonance (NMR) analyses were employed in the characterisation and identification of the isolated secondary metabolites. Results The pLDH and cell toxicity assays for the crude extract and the fractions of M. lucida indicated that some fractions reduced the malaria parasite viability by approximately 50% at 100 μg/mL and they were not significantly cytotoxic. An IC50 done on the crude extract gave a value of 25 μg/mL. The % cell viability for the crude extract in cell toxicity assay remained at 100%. Seven chemical constituents i.e. asperuloside (1), asperulosidic acid (2), stigmasterol (3a), β-sitosterol (3b), cycloartenol (3c), campesterol (3d) and 5,15-O-dimethylmorindol (4) were isolated from the DCM-MeOH extract of stem bark. The isolated compounds tested were not that active by themselves individually at 20 μM but their activities were increased when the isolated compounds were combined. As seen when compounds 2, 3 and 4 (% viability: 93, 123 and 101 respectively) were combined yielding an IC50 value of 17 μM. Furthermore, this is the first report of compounds 1, 2, 3c, 3d and 4 isolated from M. lucida. Conclusion The crude extract completely suppressed the growth of P. falciparum. This indicates that the crude extract contains many compounds that might be acting in synergy. The observed activity of the crude extract and the samples containing a mixture of different compounds support the traditional use of M. lucida for the treatment of malaria.
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Cationic cyclodextrin/alginate chitosan nanoflowers as 5-fluorouracil drug delivery system
- Lakkakula, Jaya R, Matshaya, Thabo, Krause, Rui W M
- Authors: Lakkakula, Jaya R , Matshaya, Thabo , Krause, Rui W M
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125587 , vital:35798 , https://doi.org/10.1016/j.msec.2016.08.073
- Description: Cyclodextrins (CDs) have widely been used as component of drug delivery systems. However unmodified cyclodextrins are associated with cytotoxicity and poor water solubility thus limiting their use in pharmaceutical industry. The cationic-β-cyclodextrin (Cat-β-CD) polymer cores were synthesized using β-CD, epichlorohydrin and choline chloride via a one-step polycondensation process. The main aim of this study was to synthesize hierarchical nanoflowers composed of cationic-β-CD as polymeric core along with alginate and chitosan “petals” (Cat-β-CD/Alg-Chi nanoflowers) as carriers for oral delivery of 5-Fluorouracil (5-FU) via an ionic-gelation technique. The drug loading capacity, particle size, zeta potential and surface morphology of the synthesized nanoflowers were determined. The prepared nanoflowers were formed with an average size of 300 nm and a zeta potential of + 9.90 mV with good encapsulation efficiency of up to 77.3%. In vitro release of 5-FU from the loaded nanoflowers showed controlled and sustained release compared to the inclusion complex alone. Cat-β-CD/Alg-Chi nanoflowers were assessed against L929 cells and found to be effectively inhibiting the growth of L929 cells in a concentration dependent manner.
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- Authors: Lakkakula, Jaya R , Matshaya, Thabo , Krause, Rui W M
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125587 , vital:35798 , https://doi.org/10.1016/j.msec.2016.08.073
- Description: Cyclodextrins (CDs) have widely been used as component of drug delivery systems. However unmodified cyclodextrins are associated with cytotoxicity and poor water solubility thus limiting their use in pharmaceutical industry. The cationic-β-cyclodextrin (Cat-β-CD) polymer cores were synthesized using β-CD, epichlorohydrin and choline chloride via a one-step polycondensation process. The main aim of this study was to synthesize hierarchical nanoflowers composed of cationic-β-CD as polymeric core along with alginate and chitosan “petals” (Cat-β-CD/Alg-Chi nanoflowers) as carriers for oral delivery of 5-Fluorouracil (5-FU) via an ionic-gelation technique. The drug loading capacity, particle size, zeta potential and surface morphology of the synthesized nanoflowers were determined. The prepared nanoflowers were formed with an average size of 300 nm and a zeta potential of + 9.90 mV with good encapsulation efficiency of up to 77.3%. In vitro release of 5-FU from the loaded nanoflowers showed controlled and sustained release compared to the inclusion complex alone. Cat-β-CD/Alg-Chi nanoflowers were assessed against L929 cells and found to be effectively inhibiting the growth of L929 cells in a concentration dependent manner.
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Synthesis of silver nanoparticles from a Desmodium adscendens extract and its antibacterial evaluation on wound dressing material
- Lakkakula, Jaya R, Ndinteh, Derek T, van Vuuren, Sandy F, Olivier, Denise K, Krause, Rui W M
- Authors: Lakkakula, Jaya R , Ndinteh, Derek T , van Vuuren, Sandy F , Olivier, Denise K , Krause, Rui W M
- Date: 2017
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/195025 , vital:45520 , xlink:href="https://doi.org/10.1049/iet-nbt.2017.0084"
- Description: The one-pot synthesis of silver nanoparticles (AgNPs) using the medium-polar extract of Desmodium adscendens (Sw.) DC. is presented here as an alternative synthesis of metal NPs. Characterisation of the formed NPs showed polydispersed AgNPs ranging from 15 to 100 nm where the concentration of metal ions was found to play a role in the size and shape of the prepared NPs. It could be established that the flavonoids, saponins, and alkaloids present in the extract acted as both reducing and stabilising agents during the formation of the capped metal NPs. This means of NP synthesis was also employed during the in situ immobilisation of AgNPs on gauze and plaster. An evaluation of the antibacterial activity of the medium-polar D. adscendens extract, AgNPs suspended in solution, and the immobilised AgNPs against Staphylococcus aureus (ATCC 25923), Bacillus cereus (ATCC 11778), and Escherichia coli (ATCC 25922) showed high efficacy against the latter in particular. This suggests that gauze, dilute silver nitrate solutions, and D. adscendens extract could be used successfully in the simple in situ preparation of effective antibacterial wound dressings.
- Full Text:
- Authors: Lakkakula, Jaya R , Ndinteh, Derek T , van Vuuren, Sandy F , Olivier, Denise K , Krause, Rui W M
- Date: 2017
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/195025 , vital:45520 , xlink:href="https://doi.org/10.1049/iet-nbt.2017.0084"
- Description: The one-pot synthesis of silver nanoparticles (AgNPs) using the medium-polar extract of Desmodium adscendens (Sw.) DC. is presented here as an alternative synthesis of metal NPs. Characterisation of the formed NPs showed polydispersed AgNPs ranging from 15 to 100 nm where the concentration of metal ions was found to play a role in the size and shape of the prepared NPs. It could be established that the flavonoids, saponins, and alkaloids present in the extract acted as both reducing and stabilising agents during the formation of the capped metal NPs. This means of NP synthesis was also employed during the in situ immobilisation of AgNPs on gauze and plaster. An evaluation of the antibacterial activity of the medium-polar D. adscendens extract, AgNPs suspended in solution, and the immobilised AgNPs against Staphylococcus aureus (ATCC 25923), Bacillus cereus (ATCC 11778), and Escherichia coli (ATCC 25922) showed high efficacy against the latter in particular. This suggests that gauze, dilute silver nitrate solutions, and D. adscendens extract could be used successfully in the simple in situ preparation of effective antibacterial wound dressings.
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Cyclodextrin grafted calcium carbonate vaterite particles: efficient system for tailored release of hydrophobic anticancer or hormone drugs
- Lakkakula, Jaya R, Kurapati, Rajendra, Tynga, Ivan, Krause, Rui W M, Abrahamse, Heidi, Raichur, Ashok M
- Authors: Lakkakula, Jaya R , Kurapati, Rajendra , Tynga, Ivan , Krause, Rui W M , Abrahamse, Heidi , Raichur, Ashok M
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125435 , vital:35783 , https://doi.org/10.1039/C6RA12951J
- Description: Porous CaCO3 microparticles have been used earlier for sustained drug release of hydrophilic drugs but have certain drawbacks for use with hydrophobic drugs. Hence, to overcome these drawbacks, a novel composite of CaCO3 along with cyclodextrin (CD–CaCO3) for the delivery of hydrophobic drugs was developed. Cyclodextrins (CDs), when incorporated within CaCO3, increased the porosity and surface area of microparticles thereby enhancing the encapsulation efficiency of hydrophobic drugs (5-Fluorouracil or Na-L-thyroxine) by forming inclusion complexes with cyclodextrin. Thermogravimetric and FTIR studies confirmed the interaction between the cyclodextrin and CaCO3 microparticles. Raman spectra confirmed the peak of vaterite crystals before and after loading of hydrophobic drugs within the composite. In vitro release studies when performed at pH 4.8 (5-Fu) and pH 1.2 (Na-L-thy) showed release at low pH as CaCO3 is soluble at acidic pH unlike slower release at basic pH. Release kinetics followed a Higuchi kinetic model at pH 4.8 (5-Fu) and pH 1.2 (Na-L-thy) respectively.
- Full Text:
- Authors: Lakkakula, Jaya R , Kurapati, Rajendra , Tynga, Ivan , Krause, Rui W M , Abrahamse, Heidi , Raichur, Ashok M
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125435 , vital:35783 , https://doi.org/10.1039/C6RA12951J
- Description: Porous CaCO3 microparticles have been used earlier for sustained drug release of hydrophilic drugs but have certain drawbacks for use with hydrophobic drugs. Hence, to overcome these drawbacks, a novel composite of CaCO3 along with cyclodextrin (CD–CaCO3) for the delivery of hydrophobic drugs was developed. Cyclodextrins (CDs), when incorporated within CaCO3, increased the porosity and surface area of microparticles thereby enhancing the encapsulation efficiency of hydrophobic drugs (5-Fluorouracil or Na-L-thyroxine) by forming inclusion complexes with cyclodextrin. Thermogravimetric and FTIR studies confirmed the interaction between the cyclodextrin and CaCO3 microparticles. Raman spectra confirmed the peak of vaterite crystals before and after loading of hydrophobic drugs within the composite. In vitro release studies when performed at pH 4.8 (5-Fu) and pH 1.2 (Na-L-thy) showed release at low pH as CaCO3 is soluble at acidic pH unlike slower release at basic pH. Release kinetics followed a Higuchi kinetic model at pH 4.8 (5-Fu) and pH 1.2 (Na-L-thy) respectively.
- Full Text:
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