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Article ; Online: Rising role of 3D-printing in delivery of therapeutics for infectious disease.

Kyser, Anthony J / Fotouh, Bassam / Mahmoud, Mohamed Y / Frieboes, Hermann B

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

2024 Volume 366, Page(s) 349–365

Abstract: Modern drug delivery to tackle infectious disease has drawn close to personalizing medicine for specific patient populations. Challenges include antibiotic-resistant infections, healthcare associated infections, and customizing treatments for local ... ...

Abstract	Modern drug delivery to tackle infectious disease has drawn close to personalizing medicine for specific patient populations. Challenges include antibiotic-resistant infections, healthcare associated infections, and customizing treatments for local patient populations. Recently, 3D-printing has become a facilitator for the development of personalized pharmaceutic drug delivery systems. With a variety of manufacturing techniques, 3D-printing offers advantages in drug delivery development for controlled, fine-tuned release and platforms for different routes of administration. This review summarizes 3D-printing techniques in pharmaceutics and drug delivery focusing on treating infectious diseases, and discusses the influence of 3D-printing design considerations on drug delivery platforms targeting these diseases. Additionally, applications of 3D-printing in infectious diseases are summarized, with the goal to provide insight into how future delivery innovations may benefit from 3D-printing to address the global challenges in infectious disease.
MeSH term(s)	Humans ; Communicable Diseases/drug therapy ; Cross Infection ; Medicine ; Biopharmaceutics ; Printing, Three-Dimensional
Language	English
Publishing date	2024-01-08
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.2023.12.051
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Article ; Online: Unleashing new MTDL AChE and BuChE inhibitors as potential anti-AD therapeutic agents: In vitro, in vivo and in silico studies.

Zaafar, Dalia / Elghazawy, Nehal H / Hassan, Afnan / Mahmoud, Mohamed Y / Bakr, Alaa F / Arafa, Reem K

International journal of biological macromolecules

2024 Volume 268, Issue Pt 1, Page(s) 131740

Abstract: Alzheimer's disease (AD) is challenging due to its irreversible declining cognitive symptoms and multifactorial nature. This work tackles targeting both acetylcholinesterase (AChE) and BuChE with a multitarget-directed ligand (MTDL) through design, ... ...

Abstract	Alzheimer's disease (AD) is challenging due to its irreversible declining cognitive symptoms and multifactorial nature. This work tackles targeting both acetylcholinesterase (AChE) and BuChE with a multitarget-directed ligand (MTDL) through design, synthesis, and biological and in silico evaluation of a series of twenty eight new 5-substituted-2-anilino-1,3,4-oxadiazole derivatives 4a-g, 5a-g, 9a-g and 13a-g dual inhibitors of the target biomolecules. In vitro cholinesterases inhibition and selectivity assay of the synthesized derivatives showed excellent nanomolar level inhibitory activities. Compound 5a, the most potent inhibitor, elicited IC
MeSH term(s)	Cholinesterase Inhibitors/pharmacology ; Cholinesterase Inhibitors/chemistry ; Cholinesterase Inhibitors/chemical synthesis ; Acetylcholinesterase/metabolism ; Acetylcholinesterase/chemistry ; Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Animals ; Rats ; Molecular Docking Simulation ; Butyrylcholinesterase/metabolism ; Butyrylcholinesterase/chemistry ; Humans ; Computer Simulation ; Oxidative Stress/drug effects ; Ligands ; Brain/drug effects ; Brain/metabolism ; Male ; Amyloid beta-Peptides/metabolism ; Structure-Activity Relationship ; Rats, Wistar
Language	English
Publishing date	2024-04-21
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.2024.131740
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Article ; Online: Effects of Aluminum Oxide Nanoparticles in the Cerebrum, Hippocampus, and Cerebellum of Male Wistar Rats and Potential Ameliorative Role of Melatonin.

Abdelhameed, Nermeen G / Ahmed, Yasmine H / Yasin, Noha A E / Mahmoud, Mohamed Y / El-Sakhawy, Mohamed A

ACS chemical neuroscience

2023 Volume 14, Issue 3, Page(s) 359–369

Abstract: Aluminum oxide nanoparticles ( ... ...

Abstract	Aluminum oxide nanoparticles (Al
MeSH term(s)	Humans ; Male ; Rats ; Animals ; Aluminum Oxide/toxicity ; Rats, Wistar ; Melatonin/pharmacology ; Acetylcholinesterase/metabolism ; Nanoparticles ; Antioxidants/pharmacology ; Antioxidants/metabolism ; Cerebellum/metabolism ; Hippocampus/metabolism ; Body Weight ; Oxidative Stress
Chemical Substances	Aluminum Oxide (LMI26O6933) ; Melatonin (JL5DK93RCL) ; Acetylcholinesterase (EC 3.1.1.7) ; Antioxidants
Language	English
Publishing date	2023-01-23
Publishing country	United States
Document type	Journal Article
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.2c00406
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Article ; Online: Fortified anti-proliferative activity of niclosamide for breast cancer treatment: In-vitro and in-vivo assessment

Mansour, Amira / Mahmoud, Mohamed Y. / Bakr, Alaa F. / Ghoniem, Monira G. / Adam, Fatima A. / El-Sherbiny, Ibrahim M.

Life Sciences. 2023 Mar., v. 316 p.121379-

2023

Abstract: Breast cancer represents one of the top lethal cancer types among the females worldwide. Several factors manipulate the clinical outcome of the treatment as the stage of the cancer upon detection, genetic and hormonal factors, drug resistance and ... ...

Abstract	Breast cancer represents one of the top lethal cancer types among the females worldwide. Several factors manipulate the clinical outcome of the treatment as the stage of the cancer upon detection, genetic and hormonal factors, drug resistance and metastasis. Accordingly, drug's repositioning, enhancing the bioavailability and encapsulation into nanoparticles (NPs) are among the predilected pathways for enhanced therapeutic outcome. Niclosamide (NIC) is an anthelmintic drug and has been repositioned as anticancer agent after revealing its anti-neoplastic activity. Piperine (PIP) was used as food spice until its anticancer activity was discovered. However, their hydrophobicity constrains their therapeutic efficiency. The cytotoxicity of both drugs in the free form was tested on MCF-7 cells, and the results indicated a NIC cytotoxicity enhancement by PIP. Then, NIC and PIP were encapsulated successfully into F127-NPs with entrapment efficiency of 97 % and 82 %, respectively. Particle size, zeta potential, TEM and FTIR confirmed the micellization process and drug encapsulation. The developed NIC-NPs and PIP-NPs exerted potent anticancer effect as compared to the free forms. Accordingly, the mixture; NIC-NPs/PIP-NPs was tested and its cytotoxicity exceeded the individually encapsulated drugs. Flowcytometry assessment was performed and demonstrated an induced cell death through the apoptotic stage. Additionally, in-vivo therapeutic efficiency of NIC-NPs/PIP-NPs was assessed through Ehrlich ascites tumor and the nanocombination therapy exerted superior additive anticancer effect when compared to NIC-NPs which is attributed to the PIP-NPs induced bioavailability. The study can be considered the first one investigating the PIP role in bioenhancing the anti-proliferative activity of NIC to combat breast cancer.
Keywords	antineoplastic activity ; antineoplastic agents ; apoptosis ; bioavailability ; breast neoplasms ; cancer therapy ; carcinoma ; cytotoxicity ; drug resistance ; encapsulation ; hydrophobicity ; metastasis ; nanoparticles ; niclosamide ; particle size ; spices ; zeta potential ; Anti-proliferative activity ; Piperine ; Pluronic ; Bioenhancer
Language	English
Dates of publication	2023-03
Publishing place	Elsevier Inc.
Document type	Article ; Online
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.121379
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Article ; Online: Switching indication of PEGylated lipid nanocapsules-loaded with rolapitant and deferasirox against breast cancer: Enhanced in-vitro and in-vivo cytotoxicity.

Kabil, Mohamed Fawzi / Mahmoud, Mohamed Y / Bakr, Alaa F / Zaafar, Dalia / El-Sherbiny, Ibrahim M

Life sciences

2022 Volume 305, Page(s) 120731

Abstract: Breast cancer (BC) is considered the leading cause of mortality and morbidity among adult women worldwide, and it is associated with many genetic or hormonal factors. Despite the advanced therapeutic and theranostic strategies for BC treatment, cancer ... ...

Abstract	Breast cancer (BC) is considered the leading cause of mortality and morbidity among adult women worldwide, and it is associated with many genetic or hormonal factors. Despite the advanced therapeutic and theranostic strategies for BC treatment, cancer metastasis and relapse are often observed among patients which lead to therapeutic failure. Accordingly, among the repositioned medication against BC proliferation is neurokinin receptor antagonists and iron chelating agents especially rolapitant HCl (RP) and deferasirox (DFO), respectively. However, RP and DFO are classified as class II with low aqueous solubility. Both drugs were nanoformulated into PEGylated lipid nanocapsules (LNCs) for enhancing their aqueous solubility and augmenting their efficacy. RP-LNCs, DFO-LNCs and their combinations were evaluated according to particle size (PS), zeta potential, polydispersity index (PDI) and surface morphology. Importantly, the antitumor effect of these novel molecules and their nanoforms was evaluated against the suppression of Ehrlich Ascites tumor model using female mice. Results revealed that RP-LNCs, DFO-LNCs and RP/DFO-LNCs exerted PS from 45.23 ± 3.54 to 60.1 ± 3.32 nm with PDI around 0.20 which indicates homogenous particles distribution. Also, RP-LNCs, DFO-LNCs and RP/DFO-LNCs displayed surface charges of +16.6 ± 6.9, -13.3 ± 5.82 and - 20.2 ± 5.40 mV, respectively. The obtained LNCs conferred a high potent cytotoxic effect against MCF7 cancer cells as compared to parent drugs, with IC
MeSH term(s)	Animals ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Deferasirox/pharmacology ; Female ; Humans ; Lipids/therapeutic use ; Mice ; Nanocapsules ; Neoplasm Recurrence, Local/drug therapy ; Polyethylene Glycols/therapeutic use ; Spiro Compounds
Chemical Substances	Lipids ; Nanocapsules ; Spiro Compounds ; Polyethylene Glycols (3WJQ0SDW1A) ; rolapitant (NLE429IZUC) ; Deferasirox (V8G4MOF2V9)
Language	English
Publishing date	2022-06-24
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.120731
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Article ; Online: Computational Modeling of Probiotic Recovery from 3D-Bioprinted Scaffolds for Localized Vaginal Application.

Rai, Veeresh / Kyser, Anthony J / Goodin, Dylan A / Mahmoud, Mohamed Y / Steinbach-Rankins, Jill M / Frieboes, Hermann B

Annals of 3D printed medicine

2023 Volume 11

Abstract: Lactobacilli, play a beneficial role in the female reproductive tract (FRT), regulating pH via lactic acid metabolism to help maintain a healthy environment. Bacterial vaginosis (BV) is characterized by a dysregulated flora in which anaerobes such ... ...

Abstract	Lactobacilli, play a beneficial role in the female reproductive tract (FRT), regulating pH via lactic acid metabolism to help maintain a healthy environment. Bacterial vaginosis (BV) is characterized by a dysregulated flora in which anaerobes such as
Language	English
Publishing date	2023-07-04
Publishing country	United States
Document type	Journal Article
ISSN	2666-9641
ISSN (online)	2666-9641
DOI	10.1016/j.stlm.2023.100120
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Article: Correction: Mansour et al. Dual-Enhanced Pluronic Nanoformulated Methotrexate-Based Treatment Approach for Breast Cancer: Development and Evaluation of In Vitro and In Vivo Efficiency.

Mansour, Amira / Mahmoud, Mohamed Y / Bakr, Alaa F / Ghoniem, Monira G / Adam, Fatima A / El-Sherbiny, Ibrahim M

Pharmaceutics

2023 Volume 15, Issue 3

Abstract: In the original publication [ ... ]. ...

Abstract	In the original publication [...].
Language	English
Publishing date	2023-03-20
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15030994
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Article ; Online: Development and Characterization of

Kyser, Anthony J / Mahmoud, Mohamed Y / Johnson, Nicholas T / Fotouh, Bassam / Steinbach-Rankins, Jill M / Gilbert, Nicole M / Frieboes, Hermann B

ACS biomaterials science & engineering

2023 Volume 9, Issue 7, Page(s) 4277–4287

Abstract: Catheter-associated urinary tract infections (CAUTI) are a significant healthcare burden affecting millions of patients annually. CAUTI are characterized by infection of the bladder and pathogen colonization of the catheter surface, making them ... ...

Abstract	Catheter-associated urinary tract infections (CAUTI) are a significant healthcare burden affecting millions of patients annually. CAUTI are characterized by infection of the bladder and pathogen colonization of the catheter surface, making them especially difficult to treat. Various catheter modifications have been employed to reduce pathogen colonization, including infusion of antibiotics and antimicrobial compounds, altering the surface architecture of the catheter, or coating it with nonpathogenic bacteria. Lactobacilli probiotics offer promise for a "bacterial interference" approach because they not only compete for adhesion to the catheter surface but also produce and secrete antimicrobial compounds effective against uropathogens. Three-dimensional (3D) bioprinting has enabled fabrication of well-defined, cell-laden architectures with tailored release of active agents, thereby offering a novel means for sustained probiotic delivery. Silicone has shown to be a promising biomaterial for catheter applications due to mechanical strength, biocompatibility, and its ability to mitigate encrustation on the catheter. Additionally, silicone, as a bioink, provides an optimum matrix for bioprinting lactobacilli. This study formulates and characterizes novel 3D-bioprinted
MeSH term(s)	Humans ; Lacticaseibacillus rhamnosus ; Urinary Tract Infections/prevention & control ; Urinary Tract Infections/microbiology ; Anti-Infective Agents ; Urinary Catheters/microbiology ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacteria ; Silicones
Chemical Substances	Anti-Infective Agents ; Anti-Bacterial Agents ; Silicones
Language	English
Publishing date	2023-06-27
Publishing country	United States
Document type	Journal Article
ISSN	2373-9878
ISSN (online)	2373-9878
DOI	10.1021/acsbiomaterials.3c00210
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Article ; Online: Formulation and characterization of pressure-assisted microsyringe 3D-printed scaffolds for controlled intravaginal antibiotic release.

Kyser, Anthony J / Mahmoud, Mohamed Y / Herold, Sydney E / Lewis, Warren G / Lewis, Amanda L / Steinbach-Rankins, Jill M / Frieboes, Hermann B

International journal of pharmaceutics

2023 Volume 641, Page(s) 123054

Abstract: Bacterial vaginosis (BV) is a highly recurrent vaginal condition linked with many health complications. Topical antibiotic treatments for BV are challenged with drug solubility in vaginal fluid, lack of convenience and user adherence to daily treatment ... ...

Abstract	Bacterial vaginosis (BV) is a highly recurrent vaginal condition linked with many health complications. Topical antibiotic treatments for BV are challenged with drug solubility in vaginal fluid, lack of convenience and user adherence to daily treatment protocols, among other factors. 3D-printed scaffolds can provide sustained antibiotic delivery to the female reproductive tract (FRT). Silicone vehicles have been shown to provide structural stability, flexibility, and biocompatibility, with favorable drug release kinetics. This study formulates and characterizes novel metronidazole-containing 3D-printed silicone scaffolds for eventual application to the FRT. Scaffolds were evaluated for degradation, swelling, compression, and metronidazole release in simulated vaginal fluid (SVF). Scaffolds retained high structural integrity and sustained release. Minimal mass loss (<6%) and swelling (<2%) were observed after 14 days in SVF, relative to initial post-cure measurements. Scaffolds cured for 24 hr (50 °C) demonstrated elastic behavior under 20% compression and 4.0 N load. Scaffolds cured for 4 hr (50 °C), followed by 72 hr (4 °C), demonstrated the highest, sustained, metronidazole release (4.0 and 27.0 µg/mg) after 24 hr and 14 days, respectively. Based upon daily release profiles, it was observed that the 24 hr timepoint had the greatest metronidazole release of 4.08 μg/mg for scaffolds cured at 4 hr at 50 °C followed by 72 hr at 4 °C. For all curing conditions, release of metronidazole after 1 and 7 days showed > 4.0-log reduction in Gardnerella concentration. Negligible cytotoxicity was observed in treated keratinocytes comparable to untreated cells, This study shows that pressure-assisted microsyringe 3D-printed silicone scaffolds may provide a versatile vehicle for sustained metronidazole delivery to the FRT.
MeSH term(s)	Humans ; Female ; Anti-Bacterial Agents ; Metronidazole ; Administration, Intravaginal ; Vaginosis, Bacterial/drug therapy ; Printing, Three-Dimensional
Chemical Substances	Anti-Bacterial Agents ; Metronidazole (140QMO216E)
Language	English
Publishing date	2023-05-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2023.123054
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Article ; Online: Fortified anti-proliferative activity of niclosamide for breast cancer treatment: In-vitro and in-vivo assessment.

Mansour, Amira / Mahmoud, Mohamed Y / Bakr, Alaa F / Ghoniem, Monira G / Adam, Fatima A / El-Sherbiny, Ibrahim M

Life sciences

2023 Volume 316, Page(s) 121379

Abstract	Breast cancer represents one of the top lethal cancer types among the females worldwide. Several factors manipulate the clinical outcome of the treatment as the stage of the cancer upon detection, genetic and hormonal factors, drug resistance and metastasis. Accordingly, drug's repositioning, enhancing the bioavailability and encapsulation into nanoparticles (NPs) are among the predilected pathways for enhanced therapeutic outcome. Niclosamide (NIC) is an anthelmintic drug and has been repositioned as anticancer agent after revealing its anti-neoplastic activity. Piperine (PIP) was used as food spice until its anticancer activity was discovered. However, their hydrophobicity constrains their therapeutic efficiency. The cytotoxicity of both drugs in the free form was tested on MCF-7 cells, and the results indicated a NIC cytotoxicity enhancement by PIP. Then, NIC and PIP were encapsulated successfully into F127-NPs with entrapment efficiency of 97 % and 82 %, respectively. Particle size, zeta potential, TEM and FTIR confirmed the micellization process and drug encapsulation. The developed NIC-NPs and PIP-NPs exerted potent anticancer effect as compared to the free forms. Accordingly, the mixture; NIC-NPs/PIP-NPs was tested and its cytotoxicity exceeded the individually encapsulated drugs. Flowcytometry assessment was performed and demonstrated an induced cell death through the apoptotic stage. Additionally, in-vivo therapeutic efficiency of NIC-NPs/PIP-NPs was assessed through Ehrlich ascites tumor and the nanocombination therapy exerted superior additive anticancer effect when compared to NIC-NPs which is attributed to the PIP-NPs induced bioavailability. The study can be considered the first one investigating the PIP role in bioenhancing the anti-proliferative activity of NIC to combat breast cancer.
MeSH term(s)	Female ; Humans ; Niclosamide/pharmacology ; Breast Neoplasms/drug therapy ; Antineoplastic Agents/pharmacology ; Anthelmintics/pharmacology ; MCF-7 Cells ; Nanoparticles ; Particle Size
Chemical Substances	Niclosamide (8KK8CQ2K8G) ; Antineoplastic Agents ; Anthelmintics
Language	English
Publishing date	2023-01-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.121379
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