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Article ; Online: Applications of peptides in nanosystems for diagnosing and managing bacterial sepsis.

Gafar, Mohammed A / Omolo, Calvin A / Elhassan, Eman / Ibrahim, Usri H / Govender, Thirumala

2024 Volume 31, Issue 1, Page(s) 40

Abstract: Sepsis represents a critical medical condition stemming from an imbalanced host immune response to infections, which is linked to a significant burden of disease. Despite substantial efforts in laboratory and clinical research, sepsis remains a prominent ...

Abstract	Sepsis represents a critical medical condition stemming from an imbalanced host immune response to infections, which is linked to a significant burden of disease. Despite substantial efforts in laboratory and clinical research, sepsis remains a prominent contributor to mortality worldwide. Nanotechnology presents innovative opportunities for the advancement of sepsis diagnosis and treatment. Due to their unique properties, including diversity, ease of synthesis, biocompatibility, high specificity, and excellent pharmacological efficacy, peptides hold great potential as part of nanotechnology approaches against sepsis. Herein, we present a comprehensive and up-to-date review of the applications of peptides in nanosystems for combating sepsis, with the potential to expedite diagnosis and enhance management outcomes. Firstly, sepsis pathophysiology, antisepsis drug targets, current modalities in management and diagnosis with their limitations, and the potential of peptides to advance the diagnosis and management of sepsis have been adequately addressed. The applications have been organized into diagnostic or managing applications, with the last one being further sub-organized into nano-delivered bioactive peptides with antimicrobial or anti-inflammatory activity, peptides as targeting moieties on the surface of nanosystems against sepsis, and peptides as nanocarriers for antisepsis agents. The studies have been grouped thematically and discussed, emphasizing the constructed nanosystem, physicochemical properties, and peptide-imparted enhancement in diagnostic and therapeutic efficacy. The strengths, limitations, and research gaps in each section have been elaborated. Finally, current challenges and potential future paths to enhance the use of peptides in nanosystems for combating sepsis have been deliberately spotlighted. This review reaffirms peptides' potential as promising biomaterials within nanotechnology strategies aimed at improving sepsis diagnosis and management.
MeSH term(s)	Humans ; Drug Delivery Systems ; Peptides/therapeutic use ; Nanotechnology ; Anti-Infective Agents ; Sepsis/diagnosis ; Sepsis/drug therapy
Chemical Substances	Peptides ; Anti-Infective Agents
Language	English
Publishing date	2024-04-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1193378-1
ISSN	1423-0127 ; 1021-7770
ISSN (online)	1423-0127
ISSN	1021-7770
DOI	10.1186/s12929-024-01029-2
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Article ; Online: Nano delivery systems to the rescue of ciprofloxacin against resistant bacteria "E. coli; P. aeruginosa; Saureus; and MRSA" and their infections.

Nwabuife, Joshua C / Omolo, Calvin A / Govender, Thirumala

Journal of controlled release : official journal of the Controlled Release Society

2022 Volume 349, Page(s) 338–353

Abstract: Ciprofloxacin (CIP) a broad-spectrum antibiotic, is used extensively for the treatment of diverse infections and diseases of bacteria origin, and this includes infections caused by E. coli; P. aeruginosa; S. aureus; and MRSA. This extensive use of CIP ... ...

Abstract	Ciprofloxacin (CIP) a broad-spectrum antibiotic, is used extensively for the treatment of diverse infections and diseases of bacteria origin, and this includes infections caused by E. coli; P. aeruginosa; S. aureus; and MRSA. This extensive use of CIP has therefore led to an increase in resistance by these infection causing organisms. Nano delivery systems has recently proven to be a possible solution to resistance to these organisms. They have been applied as a strategy to improve the target specificity of CIP against infections and diseases caused by these organisms, thereby maximising the efficacy of CIP to overcome the resistance. Herein, we proffer a brief overview of the mechanisms of resistance; the causes of resistance; and the various approaches employed to overcome this resistance. The review then proceeds to critically evaluate various nano delivery systems including inorganic based nanoparticles; lipid-based nanoparticles; capsules, dendrimers, hydrogels, micelles, and polymeric nanoparticles; and others; that have been applied for the delivery of CIP against E. coli; P. aeruginosa; S. aureus; and MRSA infections. Finally, the review highlights future areas of research, for the optimisation of various nano delivery systems, to maximise the therapeutic efficacy of CIP against these organisms. This review confirms the potential of nano delivery systems, for addressing the challenges of resistance to caused by E. coli; P. aeruginosa; S. aureus; and MRSA to CIP.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacteria ; Ciprofloxacin/pharmacology ; Ciprofloxacin/therapeutic use ; Dendrimers ; Escherichia coli ; Hydrogels ; Lipids ; Methicillin-Resistant Staphylococcus aureus ; Micelles ; Microbial Sensitivity Tests ; Nanoparticle Drug Delivery System ; Pseudomonas aeruginosa ; Staphylococcus aureus
Chemical Substances	Anti-Bacterial Agents ; Dendrimers ; Hydrogels ; Lipids ; Micelles ; Nanoparticle Drug Delivery System ; Ciprofloxacin (5E8K9I0O4U)
Language	English
Publishing date	2022-07-12
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2022.07.003
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Article ; Online: Multi-functional pH-responsive and biomimetic chitosan-based nanoplexes for targeted delivery of ciprofloxacin against bacterial sepsis.

Ismail, Eman A / Omolo, Calvin A / Gafar, Mohammed A / Khan, Rene / Nyandoro, Vincent O / Salifu, Elliasu Y / Govender, Thirumala

International journal of biological macromolecules

2024 Volume 262, Issue Pt 1, Page(s) 130046

Abstract: Bacterial sepsis is a mortal syndromic disease characterized by a complex pathophysiology that hinders effective targeted therapy. This study aimed to develop multifunctional, biomimetic and pH-responsive ciprofloxacin-loaded chitosan (CS)/sodium ... ...

Abstract	Bacterial sepsis is a mortal syndromic disease characterized by a complex pathophysiology that hinders effective targeted therapy. This study aimed to develop multifunctional, biomimetic and pH-responsive ciprofloxacin-loaded chitosan (CS)/sodium deoxycholic acid (SDC) nanoplexes (CS/SDC) nanoplexes with the ability to target and modulate the TLR4 pathway, activated during sepsis. The formulated nanoplexes were characterized in terms of physicochemical properties, in silico and in vitro potential biological activities. The optimal formulation showed good biocompatibility and stability with appropriate physicochemical parameters. The surface charge changed from negative at pH 7.4 to positive at pH 6.0 accompanied with a significantly faster release of CIP at pH 6.0 compared to 7.4. The biomimicry was elucidated by in silico tools and MST and results confirmed strong binding between the system and TLR4. Furthermore, the system revealed 4- and 2-fold antibacterial enhancement at acidic pH, and 3- and 4-fold better antibiofilm efficacy against Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) respectively, compared to bare CIP. In addition, enhanced bacterial efflux pump inhibition was demonstrated by CS/SDC nanoplexes. Finally, the developed nanosystem showed excellent antioxidant activity against DPPH radicals. Taken together, the study confirmed the multi-functionalities of CS/SDC nanoplexes and their potential benefits in improving bacterial sepsis therapy.
MeSH term(s)	Ciprofloxacin/pharmacology ; Ciprofloxacin/therapeutic use ; Chitosan/chemistry ; Methicillin-Resistant Staphylococcus aureus ; Biomimetics ; Toll-Like Receptor 4 ; Anti-Bacterial Agents/chemistry ; Hydrogen-Ion Concentration
Chemical Substances	Ciprofloxacin (5E8K9I0O4U) ; Chitosan (9012-76-4) ; Toll-Like Receptor 4 ; Anti-Bacterial Agents
Language	English
Publishing date	2024-02-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2024.130046
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Article: Photodynamic Antimicrobial Chemotherapy: Advancements in Porphyrin-Based Photosensitize Development.

Oyim, James / Omolo, Calvin A / Amuhaya, Edith K

Frontiers in chemistry

2021 Volume 9, Page(s) 635344

Abstract: The reduction of available drugs with effectiveness against microbes is worsening with the current global crisis of antimicrobial resistance. This calls for innovative strategies for combating antimicrobial resistance. Photodynamic Antimicrobial ... ...

Abstract	The reduction of available drugs with effectiveness against microbes is worsening with the current global crisis of antimicrobial resistance. This calls for innovative strategies for combating antimicrobial resistance. Photodynamic Antimicrobial Chemotherapy (PACT) is a relatively new method that utilizes the combined action of light, oxygen, and a photosensitizer to bring about the destruction of microorganisms. This technique has been found to be effective against a wide spectrum of microorganisms, including bacteria, viruses, and fungi. Of greater interest is their ability to destroy resistant strains of microorganisms and in effect help in combating the emergence of antimicrobial resistance. This manuscript reviews porphyrins and porphyrin-type photosensitizers that have been studied in the recent past with a focus on their structure-activity relationship.
Language	English
Publishing date	2021-04-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711776-5
ISSN	2296-2646
ISSN	2296-2646
DOI	10.3389/fchem.2021.635344
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Article ; Online: Inflammation-responsive drug delivery nanosystems for treatment of bacterial-induced sepsis.

Nyandoro, Vincent O / Omolo, Calvin A / Ismail, Eman A / Yong, Liu / Govender, Thirumala

International journal of pharmaceutics

2023 Volume 644, Page(s) 123346

Abstract: Sepsis, a complication of dysregulated host immune systemic response to an infection, is life threatening and causes multiple organ injuries. Sepsis is recognized by WHO as a big contributor to global morbidity and mortality. The heterogeneity in sepsis ... ...

Abstract	Sepsis, a complication of dysregulated host immune systemic response to an infection, is life threatening and causes multiple organ injuries. Sepsis is recognized by WHO as a big contributor to global morbidity and mortality. The heterogeneity in sepsis pathophysiology, antimicrobial resistance threat, the slowdown in the development of antimicrobials, and limitations of conventional dosage forms jeopardize the treatment of sepsis. Drug delivery nanosystems are promising tools to overcome some of these challenges. Among the drug delivery nanosystems, inflammation-responsive nanosystems have attracted considerable interest in sepsis treatment due to their ability to respond to specific stimuli in the sepsis microenvironment to release their payload in a precise, targeted, controlled, and rapid manner compared to non-responsive nanosystems. These nanosystems posit superior therapeutic potential to enhance sepsis treatment. This review critically evaluates the recent advances in the design of drug delivery nanosystems that are inflammation responsive and their potential in enhancing sepsis treatment. The sepsis microenvironment's unique features, such as acidic pH, upregulated receptors, overexpressed enzymes, and enhanced oxidative stress, that form the basis for their design have been adequately discussed. These inflammation-responsive nanosystems have been organized into five classes namely: Receptor-targeted nanosystems, pH-responsive nanosystems, redox-responsive nanosystems, enzyme-responsive nanosystems, and multi-responsive nanosystems. Studies under each class have been thematically grouped and discussed with an emphasis on the polymers used in their design, nanocarriers, key characterization, loaded actives, and key findings on drug release and therapeutic efficacy. Further, this information is concisely summarized into tables and supplemented by inserted figures. Additionally, this review adeptly points out the strengths and limitations of the studies and identifies research avenues that need to be explored. Finally, the challenges and future perspectives on these nanosystems have been thoughtfully highlighted.
MeSH term(s)	Humans ; Drug Delivery Systems ; Sepsis/drug therapy ; Dietary Supplements ; Drug Liberation ; Inflammation/drug therapy
Language	English
Publishing date	2023-08-25
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2023.123346
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Zs.A 1409: Show issues

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Article ; Online: Stimuli-responsive and biomimetic delivery systems for sepsis and related complications.

Ismail, Eman A / Devnarain, Nikita / Govender, Thirumala / Omolo, Calvin A

Journal of controlled release : official journal of the Controlled Release Society

2022 Volume 352, Page(s) 1048–1070

Abstract: Sepsis, a consequence of an imbalanced immune response to infection, is currently one of the leading causes of death globally. Despite advances in the discoveries of potential targets and nanotechnology, sepsis still lacks effective drug delivery systems ...

Abstract	Sepsis, a consequence of an imbalanced immune response to infection, is currently one of the leading causes of death globally. Despite advances in the discoveries of potential targets and nanotechnology, sepsis still lacks effective drug delivery systems for optimal treatment. Stimuli-responsive and biomimetic nano delivery systems, specifically, are emerging as advanced bio-inspired nanocarriers for enhancing the treatment of sepsis. Herein, we present a critical review of different stimuli-responsive systems, including pH-; enzyme-; ROS- and toxin-responsive nanocarriers, reported in the delivery of therapeutics for sepsis. Biomimetic nanocarriers, utilizing natural pathways in the inflammatory cascade to optimize sepsis therapy, are also reviewed, in addition to smart, multifunctional vehicles. The review highlights the nanomaterials designed for constructing these systems; their physicochemical properties; the mechanisms of drug release; and their potential for enhancing the therapeutic efficacy of their cargo. Current challenges are identified and future avenues for research into the optimization of bio-inspired nano delivery systems for sepsis are also proposed. This review confirms the potential of stimuli-responsive and biomimetic nanocarriers for enhanced therapy against sepsis and related complications.
MeSH term(s)	Humans ; Drug Delivery Systems ; Biomimetics ; Drug Liberation ; Nanotechnology ; Sepsis/drug therapy ; Drug Carriers/chemistry ; Nanoparticles/chemistry
Chemical Substances	Drug Carriers
Language	English
Publishing date	2022-11-17
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2022.11.013
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Article ; Online: Halting aberrant DNA methylation via in silico Identification of potent inhibitors of DNMT3B enzyme: Atomistic insights.

Mtetwa, Lusanda M / Salifu, Elliasu Y / Omolo, Calvin A / Soliman, Mahmoud E / Faya, Mbuso

Computational biology and chemistry

2023 Volume 105, Page(s) 107909

Abstract: To date, Cancer remains a global threat due to its impact on growing life expectancy. With the many efforts and methods of combating the disease, complete success remains a challenge owing to several limitations including cancer cells developing ... ...

Abstract	To date, Cancer remains a global threat due to its impact on growing life expectancy. With the many efforts and methods of combating the disease, complete success remains a challenge owing to several limitations including cancer cells developing resistance through mutations, off-target effect of some cancer drugs resulting in toxicities, among many others. Aberrant DNA methylation is understood to be the primary reason for improper gene silence, which can result in neoplastic transformation, carcinogenesis, and tumour progression. DNA methyltransferase B (DNMT3B) enzyme is considered a potential target for the treatment of several cancers due to its important role in DNA methylation. However, only a few DNMT3B inhibitors have been reported to date. Herein, in silico molecular recognition techniques such as Molecular docking, Pharmacophore-based virtual screen and MD simulation were employed to identify potential inhibitors of DNMT3B that can halt aberrancy in DNA methylation. Findings initially identified 878 hit compounds based on a designed pharmacophore model from the reference compound Hypericin. Molecular docking was used to rank the hits by testing their efficiency when bound to the target enzyme and the top three (3) selected. All three (3) of the top hits showed excellent pharmacokinetic properties but two (2) (Zinc33330198 and Zinc77235130) were identified to be non-toxic. Molecular dynamic simulation of the final two hits showed good stability, flexibility, and structural rigidity of the compounds on DNMT3B. Finally, thermodynamic energy estimations show both compounds had favourable free energies comprising - 26.04 kcal/mol for Zinc77235130 and - 15.73 kcal/mol for Zinc33330198. Amongst the final two hits, Zinc77235130 showed consistency in favourable results across all the tested parameters and was thus selected as the lead compound for further experimental validation. The identification of this lead compound will form important basis for the inhibition of aberrant DNA methylation in cancer therapy.
MeSH term(s)	Humans ; Molecular Docking Simulation ; DNA Methylation ; Molecular Dynamics Simulation ; Neoplasms
Language	English
Publishing date	2023-06-21
Publishing country	England
Document type	Journal Article
ISSN	1476-928X
ISSN (online)	1476-928X
DOI	10.1016/j.compbiolchem.2023.107909
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Nano delivery systems to the rescue of ciprofloxacin against resistant bacteria “E. coli; P. aeruginosa; Saureus; and MRSA” and their infections

Nwabuife, Joshua C. / Omolo, Calvin A. / Govender, Thirumala

Journal of controlled release. 2022 Sept., v. 349

2022

Abstract	Ciprofloxacin (CIP) a broad-spectrum antibiotic, is used extensively for the treatment of diverse infections and diseases of bacteria origin, and this includes infections caused by E. coli; P. aeruginosa; S. aureus; and MRSA. This extensive use of CIP has therefore led to an increase in resistance by these infection causing organisms. Nano delivery systems has recently proven to be a possible solution to resistance to these organisms. They have been applied as a strategy to improve the target specificity of CIP against infections and diseases caused by these organisms, thereby maximising the efficacy of CIP to overcome the resistance. Herein, we proffer a brief overview of the mechanisms of resistance; the causes of resistance; and the various approaches employed to overcome this resistance. The review then proceeds to critically evaluate various nano delivery systems including inorganic based nanoparticles; lipid-based nanoparticles; capsules, dendrimers, hydrogels, micelles, and polymeric nanoparticles; and others; that have been applied for the delivery of CIP against E. coli; P. aeruginosa; S. aureus; and MRSA infections. Finally, the review highlights future areas of research, for the optimisation of various nano delivery systems, to maximise the therapeutic efficacy of CIP against these organisms. This review confirms the potential of nano delivery systems, for addressing the challenges of resistance to caused by E. coli; P. aeruginosa; S. aureus; and MRSA to CIP.
Keywords	Escherichia coli ; antibiotics ; ciprofloxacin ; dendrimers ; hydrogels ; methicillin-resistant Staphylococcus aureus ; micelles ; therapeutics
Language	English
Dates of publication	2022-09
Size	p. 338-353.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2022.07.003
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Photodynamic Antimicrobial Chemotherapy

James Oyim / Calvin A. Omolo / Edith K. Amuhaya

Frontiers in Chemistry, Vol

Advancements in Porphyrin-Based Photosensitize Development

2021 Volume 9

Abstract	The reduction of available drugs with effectiveness against microbes is worsening with the current global crisis of antimicrobial resistance. This calls for innovative strategies for combating antimicrobial resistance. Photodynamic Antimicrobial Chemotherapy (PACT) is a relatively new method that utilizes the combined action of light, oxygen, and a photosensitizer to bring about the destruction of microorganisms. This technique has been found to be effective against a wide spectrum of microorganisms, including bacteria, viruses, and fungi. Of greater interest is their ability to destroy resistant strains of microorganisms and in effect help in combating the emergence of antimicrobial resistance. This manuscript reviews porphyrins and porphyrin-type photosensitizers that have been studied in the recent past with a focus on their structure-activity relationship.
Keywords	photodynamic antimicrobial chemotherapy ; photosensitizers ; antimicrobial resistance ; porphyrins ; microorganisms ; Chemistry ; QD1-999
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Free radical-releasing systems for targeting biofilms.

Fasiku Oluwaseun, Victoria / Omolo, Calvin A / Govender, Thirumala

Journal of controlled release : official journal of the Controlled Release Society

2020 Volume 322, Page(s) 248–273

Abstract: The recent rise in antibiotic drug resistance and biofilm formation by microorganisms has driven scientists from different fields to develop newer strategies to target microorganisms responsible for infectious diseases. There is a growing interest in ... ...

Abstract	The recent rise in antibiotic drug resistance and biofilm formation by microorganisms has driven scientists from different fields to develop newer strategies to target microorganisms responsible for infectious diseases. There is a growing interest in free radicals as therapeutic agents for antimicrobial applications. However, limitations such as short half-life has hindered their usage. Currently, several research groups are exploring various biomaterials that can prolong the half-life, increase storage duration and control the release of the therapeutic ranges of free radicals required for different applications, including biofilm eradication. This review paper initially provides a background to, and theoretical knowledge on, free radicals; and then proceeds to review studies that have employed various free radical-incorporated drug delivery systems as an approach to target biofilm formation and eradication. Some of the free radical releasing systems highlighted include polymers, nanoparticles and hydrogels, with a focus on biofilm eradication, where they impact significantly. The various challenges associated with their application are also discussed. Further, the review identifies future research and strategies that can potentiate the application of free radical-incorporated drug delivery systems for inhibiting biofilm formation and eradicating formed biofilms.
MeSH term(s)	Anti-Bacterial Agents ; Anti-Infective Agents ; Biofilms ; Free Radicals ; Polymers
Chemical Substances	Anti-Bacterial Agents ; Anti-Infective Agents ; Free Radicals ; Polymers
Language	English
Publishing date	2020-04-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2020.03.031
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