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  1. Article ; Online: Translational advancements in transdermal and mucosal delivery.

    Ho, Emmanuel A / Donnelly, Ryan F

    Drug delivery and translational research

    2022  Volume 12, Issue 4, Page(s) 733–734

    MeSH term(s) Administration, Cutaneous ; Drug Delivery Systems ; Mucous Membrane
    Language English
    Publishing date 2022-02-08
    Publishing country United States
    Document type Editorial
    ZDB-ID 2590155-2
    ISSN 2190-3948 ; 2190-393X
    ISSN (online) 2190-3948
    ISSN 2190-393X
    DOI 10.1007/s13346-022-01126-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Formulating biopharmaceuticals using three-dimensional printing.

    Chan, Alistair K C / Ranjitham Gopalakrishnan, Nehil / Traore, Yannick Leandre / Ho, Emmanuel A

    Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques

    2024  Volume 27, Page(s) 12797

    Abstract: Additive manufacturing, commonly referred to as three-dimensional (3D) printing, has the potential to initiate a paradigm shift in the field of medicine and drug delivery. Ever since the advent of the first-ever United States Food and Drug Administration ...

    Abstract Additive manufacturing, commonly referred to as three-dimensional (3D) printing, has the potential to initiate a paradigm shift in the field of medicine and drug delivery. Ever since the advent of the first-ever United States Food and Drug Administration (US FDA)-approved 3D printed tablet, there has been an increased interest in the application of this technology in drug delivery and biomedical applications. 3D printing brings us one step closer to personalized medicine, hence rendering the "one size fits all" concept in drug dosing obsolete. In this review article, we focus on the recent developments in the field of modified drug delivery systems in which various types of additive manufacturing technologies are applied.
    MeSH term(s) United States ; Technology, Pharmaceutical/methods ; Biological Products ; Printing, Three-Dimensional ; Drug Delivery Systems ; Tablets
    Chemical Substances Biological Products ; Tablets
    Language English
    Publishing date 2024-03-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1422972-9
    ISSN 1482-1826 ; 1482-1826
    ISSN (online) 1482-1826
    ISSN 1482-1826
    DOI 10.3389/jpps.2024.12797
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: pH-sensitive dual-preventive siRNA-based nanomicrobicide reactivates autophagy and inhibits HIV infection in vaginal CD4+ cells.

    Yang, Sidi / Chen, Yufei / Gu, Jijin / Harris, Angela / Su, Ruey-Chyi / Ho, Emmanuel A

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

    2024  Volume 366, Page(s) 849–863

    Abstract: Women are more susceptible to HIV transmission through unprotected heterosexual intercourse due to biological and social vulnerabilities. Intravaginal delivery of siRNAs targeting viral genes, host genes, or in combination has shown promising outcomes ... ...

    Abstract Women are more susceptible to HIV transmission through unprotected heterosexual intercourse due to biological and social vulnerabilities. Intravaginal delivery of siRNAs targeting viral genes, host genes, or in combination has shown promising outcomes against HSV, HPV and HIV. Therefore, in this study, we designed, developed and evaluated a pH-sensitive RNAi-based combination nanomicrobide for the prevention/reduction of vaginal transmission of HIV. The nanomicrobide was composed of siRNA-PEI encapsulated PLGA-PEG nanoparticles (siRNA NP) loaded in a HEC gel dosage form with siRNA targeting host gene CCR5 and the viral gene Nef as a dual preventive strategy. Knocking down CCR5, a co-receptor for HIV could prevent HIV from attaching to and entering host cells and knocking down Nef could reactivate autophagy that was inhibited by Nef to improve the elimination of intracellular virus that escaped the first line of defense. The siRNA NP showed a desirable particle size and zeta potential for intravaginal delivery and a pH-dependent release profile whereby low amounts of siRNA was released under acidic vaginal conditions (vaginal fluid simulant; VFS, pH 4.2) (6.0 ± 0.4% released over 15 days) but significantly higher amounts of siRNA was released under neutral pH conditions (phosphate buffered saline; PBS, pH 7.4) (22.9 ± 0.4% released over 15 days). The CCR5-Nef-specific siRNA NP efficiently knocked down CCR5 and Nef protein expression by 43% and 63%, respectively, reactivated Nef-blocked autophagy and inhibited the replication of HIV in vitro (71.8% reduction in p24 expression). After being formulated into a gel dosage form, siRNA NP could be readily released from the gel, penetrate the vaginal epithelial layer, get taken up into the target cells and knockdown Nef and CCR5 without causing cytotoxicity in a vaginal mucosal co-culture model. Functionalization of siRNA NP with anti-CD4 antibody and loaded into a 0.5% HEC gel improved vaginal distribution and uptake of siRNA in a mouse model with distribution of siRNA restricted to the reproductive tract without any unwanted systemic uptake. The 0.5% HEC gel loaded with siRNA NP-(m)CD4 significantly downregulated approximately 40% of CCR5 protein in the lower vagina and 36% of CCR5 protein in the upper vaginal and cervical region. In contrast, 0.5% HEC gel loaded with siRNA NP-IgG did not result in significant gene knockdown.
    MeSH term(s) Animals ; Female ; Humans ; Mice ; Autophagy ; CD4-Positive T-Lymphocytes ; HIV Infections/prevention & control ; HIV Infections/transmission ; Hydrogen-Ion Concentration ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Vagina/virology
    Chemical Substances RNA, Small Interfering
    Language English
    Publishing date 2024-02-06
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2023.12.043
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: An insight on ophthalmic drug delivery systems: Focus on polymeric biomaterials-based carriers.

    Shafiq, Muhammad / Rafique, Muhammad / Cui, Yingkun / Pan, Li / Do, Chi-Wai / Ho, Emmanuel A

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

    2023  Volume 362, Page(s) 446–467

    Abstract: Presently, different types of eye diseases, such as glaucoma, myopia, infection, and dry eyes are treated with topical eye drops. However, due to ocular surface barriers, eye drops require multiple administrations, which may cause several risks, thereby ... ...

    Abstract Presently, different types of eye diseases, such as glaucoma, myopia, infection, and dry eyes are treated with topical eye drops. However, due to ocular surface barriers, eye drops require multiple administrations, which may cause several risks, thereby necessitating additional strategies. Some of the key characteristics of an ideal ocular drug delivery system are as follows: (a) good penetration into cornea, (b) high drug retention in the ocular tissues, (c) targetability to the desired regions of the eye, and (d) good bioavailability. It is worthy to note that the corneal epithelial tight junctions hinder the permeation of therapeutics through the cornea. Therefore, it is necessary to design nanocarriers that can overcome these barriers and enhance drug penetration into the inner parts of the eye. Moreover, intelligent multifunctional nanocarriers can be designed to include cavities, which may help encapsulate sufficient amount of the drug. In addition, nanocarriers can be modified with the targeting moieties. Different types of nanocarriers have been developed for ocular drug delivery applications, including emulsions, liposomes, micelles, and nanoparticles. However, these formulations may be rapidly cleared from the eye. The therapeutic use of the nanoparticles (NPs) is also hindered by the non-specific adsorption of proteins on NPs, which may limit their interaction with the cellular moieties or other targeted biological factors. Functional drug delivery systems (DDS), which can offer targeted ocular drug delivery while avoiding the non-specific protein adsorption could exhibit great potential. This could be further realized by the on-demand DDS, which can respond to the stimuli in a spatio-temporal fashion. The cell-mediated DDS offer another valuable platform for ophthalmological drug delivery.
    Language English
    Publishing date 2023-09-08
    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.2023.08.041
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Challenges in the development and establishment of exosome-based drug delivery systems

    Wang, Jin / Chen, Derek / Ho, Emmanuel A

    Journal of controlled release. 2021 Jan. 10, v. 329

    2021  

    Abstract: Exosomes are extracellular vesicles released from cells and are characterized by a lipid bilayer membrane encapsulating a variety of biological molecules such as nucleic acids or proteins within the lumen or the lipid-bilayer. Under physiological ... ...

    Abstract Exosomes are extracellular vesicles released from cells and are characterized by a lipid bilayer membrane encapsulating a variety of biological molecules such as nucleic acids or proteins within the lumen or the lipid-bilayer. Under physiological environments, exosomes mediate cell-to-cell communication and cargo transport. Therefore, exosomes have been explored as drug delivery vehicles for improving therapeutic outcomes. Although recent studies have demonstrated promising advances with exosome-based drug delivery systems, several challenges severely hinder further development of exosomes for clinical applications. This review summarizes and emphasizes some of the technical challenges related to the isolation, characterization, and stability testing of exosomes. More importantly, challenges related specifically to the application of exosomes for drug delivery such as cell-uptake, drug loading, drug release, and in vivo distribution will be examined in this article.
    Keywords cell communication ; drug carriers ; drugs ; encapsulation ; exosomes ; lipid bilayers ; nucleic acids ; proteins
    Language English
    Dates of publication 2021-0110
    Size p. 894-906.
    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.2020.10.020
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Challenges in the development and establishment of exosome-based drug delivery systems.

    Wang, Jin / Chen, Derek / Ho, Emmanuel A

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

    2020  Volume 329, Page(s) 894–906

    Abstract: Exosomes are extracellular vesicles released from cells and are characterized by a lipid bilayer membrane encapsulating a variety of biological molecules such as nucleic acids or proteins within the lumen or the lipid-bilayer. Under physiological ... ...

    Abstract Exosomes are extracellular vesicles released from cells and are characterized by a lipid bilayer membrane encapsulating a variety of biological molecules such as nucleic acids or proteins within the lumen or the lipid-bilayer. Under physiological environments, exosomes mediate cell-to-cell communication and cargo transport. Therefore, exosomes have been explored as drug delivery vehicles for improving therapeutic outcomes. Although recent studies have demonstrated promising advances with exosome-based drug delivery systems, several challenges severely hinder further development of exosomes for clinical applications. This review summarizes and emphasizes some of the technical challenges related to the isolation, characterization, and stability testing of exosomes. More importantly, challenges related specifically to the application of exosomes for drug delivery such as cell-uptake, drug loading, drug release, and in vivo distribution will be examined in this article.
    MeSH term(s) Cell Communication ; Drug Delivery Systems ; Drug Liberation ; Exosomes/metabolism ; Extracellular Vesicles
    Language English
    Publishing date 2020-10-12
    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.2020.10.020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Correction to: Segmented intravaginal ring for the combination delivery of hydroxychloroquine and anti‑CCR5 siRNA nanoparticles as a potential strategy for preventing HIV infection.

    Traore, Yannick L / Chen, Yufei / Padilla, Fernanda / Ho, Emmanuel A

    Drug delivery and translational research

    2021  Volume 12, Issue 4, Page(s) 957

    Language English
    Publishing date 2021-05-15
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2590155-2
    ISSN 2190-3948 ; 2190-393X
    ISSN (online) 2190-3948
    ISSN 2190-393X
    DOI 10.1007/s13346-021-00997-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Segmented intravaginal ring for the combination delivery of hydroxychloroquine and anti-CCR5 siRNA nanoparticles as a potential strategy for preventing HIV infection.

    Traore, Yannick L / Chen, Yufei / Padilla, Fernanda / Ho, Emmanuel A

    Drug delivery and translational research

    2021  Volume 12, Issue 4, Page(s) 816–825

    Abstract: Vaginal drug delivery has been shown to be a promising strategy for the prevention of sexually transmitted infections. Therapy delivered at the site of infection has many advantages including improved therapeutic efficacy, reduction in systemic toxicity, ...

    Abstract Vaginal drug delivery has been shown to be a promising strategy for the prevention of sexually transmitted infections. Therapy delivered at the site of infection has many advantages including improved therapeutic efficacy, reduction in systemic toxicity, and reduced potential for development of drug resistance. We developed a "smart" combination intravaginal ring (IVR) that will (1) provide continuous release of hydroxychloroquine (HCQ) to induce T cell immune quiescence as the first-line of defense and (2) release nanoparticles containing anti-CCR5 siRNA only during sexual intercourse when triggered by the presence of seminal fluid as the second-line of defense. The IVR was capable of releasing HCQ over 25 days with a mean daily release of 31.17 ± 3.06 µg/mL. In the presence of vaginal fluid simulant plus seminal fluid simulant, over 12 × more nanoparticles (5.12 ± 0.9 mg) were released over a 4-h period in comparison to IVR segments that were incubated in the presence of vaginal fluid simulant alone (0.42 ± 0.19 mg). Anti-CCR5 siRNA nanoparticles were able to knockdown 83 ± 5.1% of CCR5 gene expression in vitro in the CD4
    MeSH term(s) Administration, Intravaginal ; Female ; HIV Infections/drug therapy ; HIV Infections/prevention & control ; Humans ; Hydroxychloroquine ; Nanoparticles ; RNA, Small Interfering
    Chemical Substances RNA, Small Interfering ; Hydroxychloroquine (4QWG6N8QKH)
    Language English
    Publishing date 2021-04-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2590155-2
    ISSN 2190-3948 ; 2190-393X
    ISSN (online) 2190-3948
    ISSN 2190-393X
    DOI 10.1007/s13346-021-00983-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Fused deposition modeling three-dimensional printing of flexible polyurethane intravaginal rings with controlled tunable release profiles for multiple active drugs.

    Chen, Yufei / Traore, Yannick L / Walker, Lyndon / Yang, Sidi / Ho, Emmanuel A

    Drug delivery and translational research

    2022  Volume 12, Issue 4, Page(s) 906–924

    Abstract: We designed and engineered novel intravaginal ring (IVR) medical devices via fused deposition modeling (FDM) three-dimensional (3D) printing for controlled delivery of hydroxychloroquine, IgG, gp120 fragment (encompassing the CD4 binding site), and ... ...

    Abstract We designed and engineered novel intravaginal ring (IVR) medical devices via fused deposition modeling (FDM) three-dimensional (3D) printing for controlled delivery of hydroxychloroquine, IgG, gp120 fragment (encompassing the CD4 binding site), and coumarin 6 PLGA-PEG nanoparticles (C6NP). The hydrophilic polyurethanes were utilized to 3D-print reservoir-type IVRs containing a tunable release controlling membrane (RCM) with varying thickness and adaptable micro porous structures (by altering the printing patterns and interior fill densities) for controlled sustained drug delivery over 14 days. FDM 3D printing of IVRs were optimized and implemented using a lab-developed Cartesian 3D printer. The structures were investigated by scanning electron microscopy (SEM) imaging and in vitro release was performed using 5 mL of daily-replenished vaginal fluid simulant (pH 4.2). The release kinetics of the IVR segments were tunable with various RCM (outer diameter to inner diameter ratio ranging from 1.12 to 2.61) produced from FDM 3D printing by controlling the printing perimeter to provide daily zero-order release of HCQ ranging from 23.54 ± 3.54 to 261.09 ± 32.49 µg/mL/day. IgG, gp120 fragment, and C6NP release rates demonstrated pattern and in-fill density-dependent characteristics. The current study demonstrated the utility of FDM 3D printing to rapidly fabricate complex micro-structures for tunable and sustained delivery of a variety of compounds including HCQ, IgG, gp120 fragment, and C6NP from IVRs in a controlled manner.
    MeSH term(s) Drug Delivery Systems ; Drug Liberation ; Female ; Humans ; Immunoglobulin G ; Pharmaceutical Preparations ; Polyurethanes/chemistry ; Printing, Three-Dimensional ; Technology, Pharmaceutical/methods
    Chemical Substances Immunoglobulin G ; Pharmaceutical Preparations ; Polyurethanes
    Language English
    Publishing date 2022-02-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2590155-2
    ISSN 2190-3948 ; 2190-393X
    ISSN (online) 2190-3948
    ISSN 2190-393X
    DOI 10.1007/s13346-022-01133-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Reagent free detection of SARS-CoV-2 using an antibody-based microwave sensor in a microfluidic platform.

    Cui, Weijia / Zhao, Pei / Wang, Jin / Qin, Ning / Ho, Emmanuel A / Ren, Carolyn L

    Lab on a chip

    2022  Volume 22, Issue 12, Page(s) 2307–2314

    Abstract: The global COVID-19 pandemic caused by SARS-CoV-2 has resulted in an unprecedented economic and societal impact. Developing simple and accurate testing methods for point-of-care (POC) diagnosis is crucial not only for the control of COVID-19, but also ... ...

    Abstract The global COVID-19 pandemic caused by SARS-CoV-2 has resulted in an unprecedented economic and societal impact. Developing simple and accurate testing methods for point-of-care (POC) diagnosis is crucial not only for the control of COVID-19, but also for better response to similar outbreaks in the future. In this work, we present a novel proof-of-concept of a microfluidic microwave sensing method for POC diagnosis of the SARS-CoV-2 virus. This method relies on the antibody immobilized on the microwave sensor to selectively capture and concentrate the SARS-CoV-2 antigen or virus present in a buffer solution flowing through the sensor region in a microchannel. The capturing of the SARS-CoV-2 antigen or virus results in a change in the permittivity of the medium near the sensor region reflected by the resonance frequency shift which is used for detection. The use of microchannels offers precise control of the sample volume and the continuous flow nature also offers the potential to monitor the dynamic capturing process. The microwave-microfluidic device shows a good sensitivity of 0.1 ng ml
    MeSH term(s) COVID-19/diagnosis ; Humans ; Indicators and Reagents ; Microfluidics ; Microwaves ; Pandemics ; SARS-CoV-2
    Chemical Substances Indicators and Reagents
    Language English
    Publishing date 2022-06-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2056646-3
    ISSN 1473-0189 ; 1473-0197
    ISSN (online) 1473-0189
    ISSN 1473-0197
    DOI 10.1039/d2lc00145d
    Database MEDical Literature Analysis and Retrieval System OnLINE

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