scholarly journals Artificial Cell Therapy: New Strategies for the Therapeutic Delivery of Live Bacteria

2005 ◽  
Vol 2005 (1) ◽  
pp. 44-56 ◽  
Author(s):  
Satya Prakash ◽  
Mitchell Lawrence Jones

There has been rapid growth in research regarding the use of live bacterial cells for therapeutic purposes. The recognition that these cells can be genetically engineered to synthesize products that have therapeutic potential has generated considerable interest and excitement among clinicians and health professionals. It is expected that a wide range of disease modifying substrates such as enzymes, hormones, antibodies, vaccines, and other genetic products will be used successfully and will impact upon health care substantially. However, a major limitation in the use of these bacterial cells is the complexity of delivering them to the correct target tissues. Oral delivery of live cells, lyophilized cells, and immobilized cells has been attempted but with limited success. Primarily, this is because bacterial cells are incapable of surviving passage through the gastrointestinal tract. In many occasions, when given orally, these cells have been found to provoke immunogenic responses that are undesirable. Recent studies show that these problems can be overcome by delivering live bacterial cells, such as genetically engineered cells, using artificial cell microcapsules. This review summarizes recent advances in the therapeutic use of live bacterial cells for therapy, discusses the principles of using artificial cells for the oral delivery of bacterial cells, outlines methods for preparing suitable artificial cells for this purpose, addresses potentials and limitations for their application in therapy, and provides insight for the future direction of this emergent and highly prospective technology.

2008 ◽  
Vol 136 ◽  
pp. S355
Author(s):  
Junzhang Lin ◽  
Weiting Yu ◽  
Xiudong Liu ◽  
Ying Zhang ◽  
Wei Wang ◽  
...  

2007 ◽  
Vol 85 (9) ◽  
pp. 884-893 ◽  
Author(s):  
Aleksandra Malgorzata Urbanska ◽  
Jasmine Bhathena ◽  
Satya Prakash

Targeted delivery of live microencapsulated bacterial cells has strong potential for application in treating various diseases, including diarrhea, kidney failure, liver failure, and high cholesterol, among others. This study investigates the potential of microcapsules composed of two natural polymers, alginate and chitosan (AC), and the use of these artificial cells in yogurt for delivery of probiotic Lactobacillus acidophilus bacterial live cells. Results show that the integrity of AC microcapsules was preserved after 76 h of mechanical shaking in MRS broth and after 12 h and 24 h in simulated gastric and intestinal fluids. Using an in vitro computer-controlled simulated human gastrointestinal (GI) model, we found 8.37 log CFU/mL of viable bacterial cells were present after 120 min of gastric exposure and 7.96 log CFU/mL after 360 min of intestinal exposure. In addition, AC microcapsules composed of chitosan 10 and 100 at various concentrations were subjected to 4-week storage in 2% milk fat yogurt or 0.85% physiological solution. It was found that 9.37 log CFU/mL of cells encapsulated with chitosan 10 and 8.24 log CFU/mL of cells encapsulated with chitosan 100 were alive after 4 weeks. The AC capsule composed of 0.5% chitosan 10 provided the highest bacterial survival of 9.11 log CFU/mL after 4 weeks. Finally, an investigation of bacterial viability over 72 h in different pH buffers yielded highest survival of 6.34 log CFU/mL and 10.34 log CFU/mL at pH 8 for free and AC-encapsulated cells, respectively. We conclude from these findings that encapsulation allows delivery of a higher number of bacteria to desired targets in the GI tract and that microcapsules containing bacterial cells are good candidates for oral artificial cells for bacterial cell therapy.


2010 ◽  
Vol 28 (No. 5) ◽  
pp. 392-406 ◽  
Author(s):  
D. Żyżelewicz ◽  
E. Nebesny ◽  
I. Motyl ◽  
Z. Libudzisz

Manufacturing of novel foodstuffs supplemented with live probiotic bacteria has recently been intensively investigated. The supplementation of confectionery with probiotics is troublesome since some unit technological processes are conducted at high temperatures and the products are usually stored at ambient temperature. Our group has developed a method of the production of milk chocolate, sweetened with either sucrose or isomalt and aspartame, containing 32, 36, or 40 g/100 g fat, and supplemented with live cells of probiotic bacterial strains: Lactobacillus casei and paracasei. This new milk chocolate displayed the same sensory properties as the reference, probiotic-free chocolate. The number of live bacterial cells was maintained at the functional level of 10<sup>6</sup> &divide; 10<sup>8</sup> cfu/g after keeping for 12 months irrespective of the temperature. The highest number of live probiotic bacteria survived in the chocolate kept at 4&deg;C. Thus the product can be regarded as functional food.


2019 ◽  
Vol 3 (4) ◽  
pp. 190-196
Author(s):  
Trisna Lim ◽  
Wei Ouyang ◽  
Christopher John Martoni ◽  
Nasri Balit ◽  
Satya Prakash

Abstract Activated charcoal was microencapsulated with Lactobacillus acidophilus 314 previously adapted for urea uptake. The creatinine removal capacity of this combination microcapsule was evaluated in-vitro in media simulating the small intestine. Results show that microcapsules containing both activated charcoal and L. acidophilus 314 demonstrated potential for decreasing creatinine. Interestingly, when co-encapsulating both activated charcoal and L. acidophilus 314 a smaller decrease in creatinine was observed than when encapsulating them separately. However, co-encapsulated microcapsules were more stable in various parts of the gastrointestinal system and survived longer in storage. These results suggest the feasibility of using microcapsules containing activated charcoal and probiotic bacteria as oral adjuvants for creatinine removal and provides a theoretical model for the use of these microcapsules to remove any unwanted metabolite.


2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Hongmei Chen ◽  
Wei Ouyang ◽  
Christopher Martoni ◽  
Fatemeh Afkhami ◽  
Bisi Lawuyi ◽  
...  

Oral therapy utilizing engineered microorganisms has shown promise in the treatment of many diseases. By microencapsulation, viable cells can overcome the harsh gastrointestinal (GI) environment and secrete needed therapeutics into the gut. These engineered cells should be encased without escaping into the GI tract for safety concerns, thus robust microcapsule membrane is requisite. This paper examined the GI performance of a novel microcapsule membrane using a dynamic simulated human GI model. Results showed that the genipin cross-linked alginate-chitosan (GCAC) microcapsules possessed strong resistance to structural disintegration in the simulated GI environment. Leakage of encapsulated high molecular weight dextran, a model material to be protected during the simulated GI transit, was negligible over 72 h of exposure, in contrast to considerable leakage of dextran from the non-cross-linked counterparts. These microcapsules did not alter the microflora and enzymatic activities in the simulated human colonic media. This study suggested the potential of the GCAC microcapsules for oral delivery of live microorganisms and other biotherapeutics.


2005 ◽  
Vol 22 (5) ◽  
pp. 539-547 ◽  
Author(s):  
H. Chen ◽  
W. Ouyang ◽  
, M. Jones ◽  
T. Haque ◽  
B. Lawuyi ◽  
...  

2019 ◽  
Vol 16 (151) ◽  
pp. 20180701 ◽  
Author(s):  
Fan Wu ◽  
Cheemeng Tan

The collective tolerance towards antimicrobial peptides (APs) is thought to occur primarily through mechanisms associated with live bacterial cells. In contrast to the focus on live cells, we discover that the LL37 antimicrobial peptide kills a subpopulation of Escherichia coli , forming dead cells that absorb the remaining LL37 from the environment. Combining mathematical modelling with population and single-cell experiments, we show that bacteria absorb LL37 at a timing that coincides with the permeabilization of their cytoplasmic membranes. Furthermore, we show that one bacterial strain can absorb LL37 and protect another strain from killing by LL37. Finally, we demonstrate that the absorption of LL37 by dead bacteria can be reduced using a peptide adjuvant. In contrast to the known collective tolerance mechanisms, we show that the absorption of APs by dead bacteria is a dynamic process that leads to emergent population behaviour.


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