TY  - JOUR
AU  - Kuzmanović Nedeljković, Snežana
AU  - Ćujić Nikolić, Nada
AU  - Radan, Milica
AU  - Milivojević, Dušan
AU  - Stević, Tatjana
AU  - Pljevljakušić, Dejan
AU  - Nikodinović-Runić, Jasmina
AU  - Bigović, Dubravka
AU  - Šavikin, Katarina
AU  - Filipić, Brankica
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5642
AB  - Within the global rise of antimicrobial resistance enhanced by the COVID-19 pandemic, where Acinetobacter baumannii has been distinguished as an emerging multi-resistant pathogen, essential oils, become the focus of novel therapeutic approaches. Hypothesizing that encapsulated Origanum heracleoticum L. and Thymus vulgaris L. essential oils could express multi-target approach against A. baumannii, this study aimed to develop microencapsulated systems with optimal technological qualities using 2-hydroxypropyl-β-cyclodextrin as a carrier, and to evaluate their pharmacological potential against A. baumannii, and their morphological and physicochemical characteristics, safety and stability profiles. The highest yield and encapsulation efficiency were obtained with 1:10 essential oil to carrier, and 1.5:10 carrier to water w/w ratios. The formation of inclusion complexes was confirmed by Fourier Transform Infrared Spectroscopy. Both microencapsulates achieved improved homogeneity, particle surface, and thermal stability compared with the pure carrier. Dominant bioactive compounds (carvacrol and p-cymene in O. heracleoticum essential oil, and thymol and p-cymene in T. vulgaris essential oil) remained the most abundant after encapsulation. While non-encapsulated essential oils revealed similar antimicrobial activity towards clinical A. baumannii isolates obtained from COVID-19 patients, encapsulated O. heracleoticum essential oil inhibited the bacterial growth at lower concentrations than T. vulgaris essential oil microencapsulate. All samples significantly reduced the formation of A. baumannii biofilm, for at least 53.90% towards the most infective isolate according to the Caenorhabditis elegans assay. Further, in silico molecular docking study revealed strong interaction pattern of carvacrol and thymol with the outer membrane protein A, which is the main factor for the A. baumannii biofilm formation. Cytotoxicity investigation on human lung A549 cells showed high survival rate in the presence of all tested concentrations, and the stability study revealed notable preservation of the bioactives’ content and pharmacological potential. Altogether, microencapsulated essential oils exhibited a multi-target approach towards A. baumannii, with satisfactory preserving capability during storage.
PB  - Elsevier B.V.
T2  - Industrial Crops and Products
T1  - Microencapsulation of Origanum heracleoticum L. and Thymus vulgaris L. essential oils – Novel strategy to combat multi-resistant Acinetobacter baumannii
VL  - 216
DO  - 10.1016/j.indcrop.2024.118762
ER  - 

@article{
author = "Kuzmanović Nedeljković, Snežana and Ćujić Nikolić, Nada and Radan, Milica and Milivojević, Dušan and Stević, Tatjana and Pljevljakušić, Dejan and Nikodinović-Runić, Jasmina and Bigović, Dubravka and Šavikin, Katarina and Filipić, Brankica",
year = "2024",
abstract = "Within the global rise of antimicrobial resistance enhanced by the COVID-19 pandemic, where Acinetobacter baumannii has been distinguished as an emerging multi-resistant pathogen, essential oils, become the focus of novel therapeutic approaches. Hypothesizing that encapsulated Origanum heracleoticum L. and Thymus vulgaris L. essential oils could express multi-target approach against A. baumannii, this study aimed to develop microencapsulated systems with optimal technological qualities using 2-hydroxypropyl-β-cyclodextrin as a carrier, and to evaluate their pharmacological potential against A. baumannii, and their morphological and physicochemical characteristics, safety and stability profiles. The highest yield and encapsulation efficiency were obtained with 1:10 essential oil to carrier, and 1.5:10 carrier to water w/w ratios. The formation of inclusion complexes was confirmed by Fourier Transform Infrared Spectroscopy. Both microencapsulates achieved improved homogeneity, particle surface, and thermal stability compared with the pure carrier. Dominant bioactive compounds (carvacrol and p-cymene in O. heracleoticum essential oil, and thymol and p-cymene in T. vulgaris essential oil) remained the most abundant after encapsulation. While non-encapsulated essential oils revealed similar antimicrobial activity towards clinical A. baumannii isolates obtained from COVID-19 patients, encapsulated O. heracleoticum essential oil inhibited the bacterial growth at lower concentrations than T. vulgaris essential oil microencapsulate. All samples significantly reduced the formation of A. baumannii biofilm, for at least 53.90% towards the most infective isolate according to the Caenorhabditis elegans assay. Further, in silico molecular docking study revealed strong interaction pattern of carvacrol and thymol with the outer membrane protein A, which is the main factor for the A. baumannii biofilm formation. Cytotoxicity investigation on human lung A549 cells showed high survival rate in the presence of all tested concentrations, and the stability study revealed notable preservation of the bioactives’ content and pharmacological potential. Altogether, microencapsulated essential oils exhibited a multi-target approach towards A. baumannii, with satisfactory preserving capability during storage.",
publisher = "Elsevier B.V.",
journal = "Industrial Crops and Products",
title = "Microencapsulation of Origanum heracleoticum L. and Thymus vulgaris L. essential oils – Novel strategy to combat multi-resistant Acinetobacter baumannii",
volume = "216",
doi = "10.1016/j.indcrop.2024.118762"
}

Kuzmanović Nedeljković, S., Ćujić Nikolić, N., Radan, M., Milivojević, D., Stević, T., Pljevljakušić, D., Nikodinović-Runić, J., Bigović, D., Šavikin, K.,& Filipić, B.. (2024). Microencapsulation of Origanum heracleoticum L. and Thymus vulgaris L. essential oils – Novel strategy to combat multi-resistant Acinetobacter baumannii. in Industrial Crops and Products
Elsevier B.V.., 216.
https://doi.org/10.1016/j.indcrop.2024.118762

Kuzmanović Nedeljković S, Ćujić Nikolić N, Radan M, Milivojević D, Stević T, Pljevljakušić D, Nikodinović-Runić J, Bigović D, Šavikin K, Filipić B. Microencapsulation of Origanum heracleoticum L. and Thymus vulgaris L. essential oils – Novel strategy to combat multi-resistant Acinetobacter baumannii. in Industrial Crops and Products. 2024;216.
doi:10.1016/j.indcrop.2024.118762 .

Kuzmanović Nedeljković, Snežana, Ćujić Nikolić, Nada, Radan, Milica, Milivojević, Dušan, Stević, Tatjana, Pljevljakušić, Dejan, Nikodinović-Runić, Jasmina, Bigović, Dubravka, Šavikin, Katarina, Filipić, Brankica, "Microencapsulation of Origanum heracleoticum L. and Thymus vulgaris L. essential oils – Novel strategy to combat multi-resistant Acinetobacter baumannii" in Industrial Crops and Products, 216 (2024),
https://doi.org/10.1016/j.indcrop.2024.118762 . .

TY  - CONF
AU  - Kuzmanović Nedeljković, Snežana
AU  - Ćujić Nikolić, Nada
AU  - Bigović, Dubravka
AU  - Petrović, Predrag
AU  - Pljevljakušić, Dejan
AU  - Šavikin, Katarina
AU  - Filipić, Brankica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5120
AB  - Among plant natural products, Oregano and Thyme essential oils (EOs) are well-known for 
their antimicrobial and antioxidant activity. The biological activities of EOs may be reduced 
due to oxidation and volatilization. Stability and preservation of EOs can be assured with the 
microencapsulation method based on complex coacervation technology. Cyclodextrins are 
suitable as carriers for volatile substances insoluble in water, and hydroxypropyl-β cyclodextrin (HPCD) leads the group considering the aqueous solubility and safe toxicity 
profile. The aim of this study was to find conditions for preparing Oregano and Thyme EOs 
microencapsulates with the best technological properties.Oregano and Thyme EOs were 
encapsulated by the freeze drying (lyophilization) method. Nine different combinations were 
prepared, where HPCD content (10, 15 and 20%) and EO:HPCD mass ratio (1:1, 1:5 and 
1:10) were varied. After stirring (200 rpm) for 24 h at a room temperature, suspensions were 
filtered through 0.45 mm PTFE filters. Samples were evaporated under vacuum and frozen (-
80 °C for 1 h), then main drying was carried out (-60 °C, pressure of 0.011 mbar for 40 h), 
and final drying (-65 °C, pressure of 0.054 mbar for 1 h). To ensure the particle purity, 
lyophilizates were washed with acetonitrile and dried at 25 °C. The content of each EO was 
determined spectrophotometrically, encapsulation efficiency (EE%) and yield were 
calculated. Duncan’s post hoc test was used to evaluate the differences between samples. 
The best conditions for both EOs were obtained with 15% HPCD and EO:HPCD mass ratio 
of 1:10. Yields of EOs for chosen Oregano and Thyme EOs complexes were 86.81 ± 2.20% 
and 89.83 ± 2.80%, respectively, with the following EE% of 49.08 ± 1.80% and 49.29 ± 
0.18%. Microencapsulation is a promising method for improving the EOs stability profile, 
and these results could be very useful in the pharmaceutical and food industry for the 
implementation of new products.
PB  - Belgrade : Institute of Technical Sciences of SASA
C3  - Twentieth Young Researchers Conference – Materials Science and Engineering, November 30 - December 2, 2022, Belgrade, Serbia - Programme and the Book of Abstracts
T1  - Microencapsulation of Oregano and Thyme essential oils with hydroxypropyl-β cyclodextrin
SP  - 14
EP  - 14
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5120
ER  - 

@conference{
author = "Kuzmanović Nedeljković, Snežana and Ćujić Nikolić, Nada and Bigović, Dubravka and Petrović, Predrag and Pljevljakušić, Dejan and Šavikin, Katarina and Filipić, Brankica",
year = "2022",
abstract = "Among plant natural products, Oregano and Thyme essential oils (EOs) are well-known for 
their antimicrobial and antioxidant activity. The biological activities of EOs may be reduced 
due to oxidation and volatilization. Stability and preservation of EOs can be assured with the 
microencapsulation method based on complex coacervation technology. Cyclodextrins are 
suitable as carriers for volatile substances insoluble in water, and hydroxypropyl-β cyclodextrin (HPCD) leads the group considering the aqueous solubility and safe toxicity 
profile. The aim of this study was to find conditions for preparing Oregano and Thyme EOs 
microencapsulates with the best technological properties.Oregano and Thyme EOs were 
encapsulated by the freeze drying (lyophilization) method. Nine different combinations were 
prepared, where HPCD content (10, 15 and 20%) and EO:HPCD mass ratio (1:1, 1:5 and 
1:10) were varied. After stirring (200 rpm) for 24 h at a room temperature, suspensions were 
filtered through 0.45 mm PTFE filters. Samples were evaporated under vacuum and frozen (-
80 °C for 1 h), then main drying was carried out (-60 °C, pressure of 0.011 mbar for 40 h), 
and final drying (-65 °C, pressure of 0.054 mbar for 1 h). To ensure the particle purity, 
lyophilizates were washed with acetonitrile and dried at 25 °C. The content of each EO was 
determined spectrophotometrically, encapsulation efficiency (EE%) and yield were 
calculated. Duncan’s post hoc test was used to evaluate the differences between samples. 
The best conditions for both EOs were obtained with 15% HPCD and EO:HPCD mass ratio 
of 1:10. Yields of EOs for chosen Oregano and Thyme EOs complexes were 86.81 ± 2.20% 
and 89.83 ± 2.80%, respectively, with the following EE% of 49.08 ± 1.80% and 49.29 ± 
0.18%. Microencapsulation is a promising method for improving the EOs stability profile, 
and these results could be very useful in the pharmaceutical and food industry for the 
implementation of new products.",
publisher = "Belgrade : Institute of Technical Sciences of SASA",
journal = "Twentieth Young Researchers Conference – Materials Science and Engineering, November 30 - December 2, 2022, Belgrade, Serbia - Programme and the Book of Abstracts",
title = "Microencapsulation of Oregano and Thyme essential oils with hydroxypropyl-β cyclodextrin",
pages = "14-14",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5120"
}

Kuzmanović Nedeljković, S., Ćujić Nikolić, N., Bigović, D., Petrović, P., Pljevljakušić, D., Šavikin, K.,& Filipić, B.. (2022). Microencapsulation of Oregano and Thyme essential oils with hydroxypropyl-β cyclodextrin. in Twentieth Young Researchers Conference – Materials Science and Engineering, November 30 - December 2, 2022, Belgrade, Serbia - Programme and the Book of Abstracts
Belgrade : Institute of Technical Sciences of SASA., 14-14.
https://hdl.handle.net/21.15107/rcub_farfar_5120

Kuzmanović Nedeljković S, Ćujić Nikolić N, Bigović D, Petrović P, Pljevljakušić D, Šavikin K, Filipić B. Microencapsulation of Oregano and Thyme essential oils with hydroxypropyl-β cyclodextrin. in Twentieth Young Researchers Conference – Materials Science and Engineering, November 30 - December 2, 2022, Belgrade, Serbia - Programme and the Book of Abstracts. 2022;:14-14.
https://hdl.handle.net/21.15107/rcub_farfar_5120 .

Kuzmanović Nedeljković, Snežana, Ćujić Nikolić, Nada, Bigović, Dubravka, Petrović, Predrag, Pljevljakušić, Dejan, Šavikin, Katarina, Filipić, Brankica, "Microencapsulation of Oregano and Thyme essential oils with hydroxypropyl-β cyclodextrin" in Twentieth Young Researchers Conference – Materials Science and Engineering, November 30 - December 2, 2022, Belgrade, Serbia - Programme and the Book of Abstracts (2022):14-14,
https://hdl.handle.net/21.15107/rcub_farfar_5120 .