Robust and Repeatable Biofabrication of Bacteria‐Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size

Bacteria-mediated drug delivery systems comprising nanotherapeutics conjugated onto bacteria synergistically augment the efficacy of both therapeutic modalities in cancer therapy. Nanocarriers preserve therapeutics’ bioavailability and reduce systemic toxicity, while bacteria selectively colonize the cancerous tissue, impart intrinsic and immune-mediated antitumor effects, and propel nanotherapeutics interstitially. The optimal bacteria-nanoparticle (NP) conjugates would carry the maximal NP load with minimal motility speed hindrance for effective interstitial distribution. Furthermore, a well-defined and repeatable NP attachment density distribution is crucial to determining these biohybrid systems’ efficacious dosage and robust performance. Herein, we utilized our Nanoscale Bacteria-Enabled Autonomous Delivery System (NanoBEADS) platform to investigate the effects of assembly process parameters of mixing method, volume, and duration on NP attachment density and repeatability. We also evaluated the effect of linkage chemistry and NP size on NP attachment density, viability, growth rate, and motility of NanoBEADS. We show that the linkage chemistry impacts NP attachment density while the self-assembly process parameters affect the repeatability and, to a lesser extent, attachment density. Lastly, the attachment density affects NanoBEADS’ growth rate and motility in an NP size-dependent manner. These findings will contribute to the development of scalable and repeatable bacteria-nanoparticle biohybrids for applications in drug delivery and beyond. Corresponding author(s) Email: [email protected]

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Robust and Repeatable Biofabrication of Bacteria-Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size

10.22541/au.163100509.93917936/v1 ◽

2021 ◽

Author(s):

Ying Zhan ◽

Austin Fergusson ◽

Lacey R. McNally ◽

Richey M. Davis ◽

Bahareh Behkam

Keyword(s):

Drug Delivery ◽

Growth Rate ◽

Process Parameters ◽

Self Assembly ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Dependent Manner ◽

Assembly Process ◽

Antitumor Effects ◽

Therapeutic Modalities

Bacteria-mediated drug delivery systems comprising nanotherapeutics conjugated onto bacteria synergistically augment the efficacy of both therapeutic modalities in cancer therapy. Nanocarriers preserve therapeutics’ bioavailability and reduce systemic toxicity, while bacteria selectively colonize the cancerous tissue, impart intrinsic and immune-mediated antitumor effects, and propel nanotherapeutics interstitially. The optimal bacteria-nanoparticle (NP) conjugates would carry the maximal NP load with minimal motility speed hindrance for effective interstitial distribution. Furthermore, a well-defined and repeatable NP attachment density distribution is crucial to determining these biohybrid systems’ efficacious dosage and robust performance. Herein, we utilized our Nanoscale Bacteria-Enabled Autonomous Delivery System (NanoBEADS) platform to investigate the effects of assembly process parameters of mixing method, volume, and duration on NP attachment density and repeatability. We also evaluated the effect of linkage chemistry and NP size on NP attachment density, viability, growth rate, and motility of NanoBEADS. We show that the linkage chemistry impacts NP attachment density while the self-assembly process parameters affect the repeatability and, to a lesser extent, attachment density. Lastly, the attachment density affects NanoBEADS’ growth rate and motility in an NP size-dependent manner. These findings will contribute to the development of scalable and repeatable bacteria-nanoparticle biohybrids for applications in drug delivery and beyond. Corresponding author(s) Email: [email protected]

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Robust and Repeatable Biofabrication of Bacteria-Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size

10.22541/au.163100509.93917936/v2 ◽

2021 ◽

Author(s):

Ying Zhan ◽

Austin Fergusson ◽

Lacey R. McNally ◽

Richey M. Davis ◽

Bahareh Behkam

Keyword(s):

Drug Delivery ◽

Growth Rate ◽

Process Parameters ◽

Self Assembly ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Dependent Manner ◽

Assembly Process ◽

Antitumor Effects ◽

Therapeutic Modalities

Bacteria-mediated drug delivery systems comprising nanotherapeutics conjugated onto bacteria synergistically augment the efficacy of both therapeutic modalities in cancer therapy. Nanocarriers preserve therapeutics’ bioavailability and reduce systemic toxicity, while bacteria selectively colonize the cancerous tissue, impart intrinsic and immune-mediated antitumor effects, and propel nanotherapeutics interstitially. The optimal bacteria-nanoparticle (NP) conjugates would carry the maximal NP load with minimal motility speed hindrance for effective interstitial distribution. Furthermore, a well-defined and repeatable NP attachment density distribution is crucial to determining these biohybrid systems’ efficacious dosage and robust performance. Herein, we utilized our Nanoscale Bacteria-Enabled Autonomous Delivery System (NanoBEADS) platform to investigate the effects of assembly process parameters of mixing method, volume, and duration on NP attachment density and repeatability. We also evaluated the effect of linkage chemistry and NP size on NP attachment density, viability, growth rate, and motility of NanoBEADS. We show that the linkage chemistry impacts NP attachment density while the self-assembly process parameters affect the repeatability and, to a lesser extent, attachment density. Lastly, the attachment density affects NanoBEADS’ growth rate and motility in an NP size-dependent manner. These findings will contribute to the development of scalable and repeatable bacteria-nanoparticle biohybrids for applications in drug delivery and beyond. Corresponding author(s) Email: [email protected]

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Techniques For The Preparation of Tissue Samples Containing Injectable Polymer Microcapsules

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120242 ◽

1985 ◽

Vol 43 ◽

pp. 710-711

Author(s):

G.E. Visscher ◽

R. L. Robison ◽

G. J. Argentieri

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Gastrocnemius Muscle ◽

Degradation Process ◽

Delivery Systems ◽

Tissue Reaction ◽

Electron Microscopic ◽

Tissue Samples ◽

Injectable Polymer ◽

Microscopic Techniques

The use of various bioerodable polymers as drug delivery systems has gained considerable interest in recent years. Among some of the shapes used as delivery systems are films, rods and microcapsules. The work presented here will deal with the techniques we have utilized for the analysis of the tissue reaction to and actual biodegradation of injectable microcapsules. This work has utilized light microscopic (LM), transmission (TEM) and scanning (SEM) electron microscopic techniques. The design of our studies has utilized methodology that would; 1. best characterize the actual degradation process without artifacts introduced by fixation procedures and 2. allow for reproducible results.In our studies, the gastrocnemius muscle of the rat was chosen as the injection site. Prior to the injection of microcapsules the skin above the sites was shaved and tattooed for later recognition and recovery. 1.0 cc syringes were loaded with the desired quantity of microcapsules and the vehicle (0.5% hydroxypropylmethycellulose) drawn up. The syringes were agitated to suspend the microcapsules in the injection vehicle.

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