Targeted delivery of antibiotics to intracellular chlamydial infections using PLGA nanoparticles
Open accessAbstract
Chlamydia trachomatis and Chlamydia pneumoniae are intracellular bacterial pathogens that have been shown to cause, or are strongly associated with, diverse chronic diseases. Persistent infections by both organisms are refractory to antibiotic therapy. The lack of therapeutic efficacy results from the attenuated metabolic rate of persistently infecting chlamydiae in combination with the modest intracellular drug concentrations achievable by normal delivery of antibiotics to the inclusions within which chlamydiae reside in the host cell cytoplasm. In this research, we evaluated whether nanoparticles formulated using the biodegradable poly(d-L-lactide-co-glycolide) (PLGA) polymer can enhance the delivery of antibiotics to the chlamydial inclusion complexes. We initially studied the trafficking of PLGA nanoparticles in Chlamydia-infected cells. We then evaluated nanoparticles for the delivery of antibiotics to the inclusions. Intracellular trafficking studies show that PLGA nanoparticles efficiently concentrate in inclusions in both acutely and persistently infected cells. Further, encapsulation of rifampin and azithromycin antibiotics in PLGA nanoparticles enhanced the effectiveness of the antibiotics in reducing microbial burden. Combination of rifampin and azithromycin was more effective than the individual drugs. Overall, our studies show that PLGA nanoparticles can be effective carriers for targeted delivery of antibiotics to intracellular chlamydial infections.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In vitro studies revealed that antibiotics (azithromycin and rifampicin) were effective if applied immediately after infection, but not if applied after 24 or 48 h. However, encapsulation in nanoparticles partly restored their activities even when applied at 24 and 48 h after infection.
“In vitro studies revealed that antibiotics (azithromycin and rifampicin) were effective if applied immediately after infection, but not if applied after 24 or 48 h. However, encapsulation in nanoparticles partly restored their activities even when applied at 24 and 48 h after infection.”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [80]
PLGA nanoparticles loaded with a fluorescent dye accumulated with chlamydial inclusion bodies in infected human lung epithelial cells.
“Toti et al. found that PLGA nanoparticles loaded with a fluorescent dye accumulated with chlamydial inclusion bodies in infected human lung epithelial cells 80 .”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [80]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Panyam, J., Zhou, W., Prabha, S., Sahoo, S. K., & Labhasetwar, V. D. (2002) · The FASEB Journal · doi:10.1096/fj.02-0088com · Cited by 1,044 · see citing works
Self-citationCharacterization of nanoparticle uptake by endothelial cells
Davda, J. P., & Labhasetwar, V. D. (2002) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(01)00923-1 · Cited by 524 · see citing works
Panyam, J., & Labhasetwar, V. D. (2003) · Pharmaceutical Research · doi:10.1023/a:1022219003551 · Cited by 467 · see citing works
Self-citationChlamydial Persistence: beyond the Biphasic Paradigm
Hogan, R. J., Mathews, S., Mukhopadhyay, S., et al. (2004) · Infection and Immunity · doi:10.1128/iai.72.4.1843-1855.2004 · Cited by 461 · see citing works
Chlamydia: Intracellular Biology, Pathogenesis, And Immunity
Stephens, R. S. (1999) · Cited by 389 · see citing works
Panyam, J., Sahoo, S. K., Prabha, S., Bargar, T. W., & Labhasetwar, V. D. (2003) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(03)00295-3 · Cited by 309 · see citing works
Self-citationLower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease
Wiesenfeld, H. (2002) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(02)02118-x · Cited by 306 · see citing works
Cocchiaro, J. L., Kumar, Y., Fischer, E. R., Hackstadt, T., & Valdivia, R. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712241105 · Cited by 298 · see citing works
Golgi-dependent transport of cholesterol to the Chlamydia trachomatis inclusion
Carabeo, R. A., Mead, D. J., & Hackstadt, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1131289100 · Cited by 264 · see citing works
Evidence of Systemic Dissemination ofChlamydia pneumoniaevia Macrophages in the Mouse
Moazed, T. C., Kuo, C., Grayston, J. T., et al. (1998) · The Journal of Infectious Diseases · doi:10.1086/515280 · Cited by 264 · see citing works
Single-step surface functionalization of polymeric nanoparticles for targeted drug delivery
Patil, Y. B., Toti, U. S., Khdair, A., Ma, L., & Panyam, J. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2008.09.056 · Cited by 242 · see citing works
Self-citationQaddoumi, M. G., Ueda, H., Yang, J. J., et al. (2004) · Pharmaceutical Research · doi:10.1023/b:pham.0000022411.47059.76 · Cited by 229 · see citing works
Carter, J. D., Espinoza, L. R., Inman, R. D., Sneed, K., RICCA, L. R., Vasey, F. B., Valeriano, J., Stanich, J. A., Oszust, C., Gerard, H. C., et al. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27394 · Cited by 204 · see citing works
Beatty, W. L. (2006) · Journal of Cell Science · doi:10.1242/jcs.02733 · Cited by 165 · see citing works
Methodologies and Cell Lines Used for Antimicrobial Susceptibility Testing of Chlamydia spp
Suchland, R. J., Geisler, W. M., & Stamm, W. E. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.2.636-642.2003 · Cited by 159 · see citing works
Scidmore, M. A., Fischer, E. R., & Hackstadt, T. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.134.2.363 · Cited by 159 · see citing works
Grassmé, H., Ireland, R. M., & van Putten, J. P. M. (1996) · Infection and Immunity · doi:10.1128/iai.64.5.1621-1630.1996 · Cited by 110 · see citing works
Preparation of hemoglobin-loaded nano-sized particles with porous structure as oxygen carriers
Zhao, J. F., Liu, C., Yuan, Y., Tao, X., Shan, X.-Q., Sheng, Y., & Wu, F. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.10.012 · Cited by 103 · see citing works
Lipid rafts, caveolae, caveolin-1, and entry by Chlamydiae into host cells
Stuart, E. S., Webley, W. C., & Norkin, L. C. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(03)00059-4 · Cited by 101 · see citing works
New insights intoChlamydiaintracellular survival mechanisms
Cocchiaro, J. L., & Valdivia, R. H. (2009) · Cellular Microbiology · doi:10.1111/j.1462-5822.2009.01364.x · Cited by 99 · see citing works
UEA I-bearing nanoparticles for brain delivery following intranasal administration
Gao, X., Chen, J., Tao, W.-Q., ZHU, J., Zhang, Q., CHEN, H., & JIANG, X. (2007) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2007.03.039 · Cited by 96 · see citing works
Gérard, H. C., Krauße‐Opatz, B., Wang, Z., et al. (2001) · Molecular Microbiology · doi:10.1046/j.1365-2958.2001.02550.x · Cited by 96 · see citing works
Wyrick, P. B. (2004) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkh283 · Cited by 72 · see citing works
Persistent Chlamydiae and chronic arthritis.
Villareal, C., Whittum‐Hudson, J. A., & Hudson, A. P. (2002) · Arthritis Research · doi:10.1186/ar382 · Cited by 71 · see citing works
Self-citationGérard, H. C., Köhler, L., Branigan, P. J., et al. (1998) · Medical Microbiology and Immunology · doi:10.1007/s004300050082 · Cited by 63 · see citing works
Kutlin, A., Kohlhoff, S. A., Roblin, P. M., et al. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.3.903-907.2005 · Cited by 52 · see citing works
Imaging subcellular structures of rat mammary carcinoma cells by scanning force microscopy
Pietrasanta, L. I., Schaper, A., & Jovin, T. M. (1994) · Journal of Cell Science · doi:10.1242/jcs.107.9.2427 · Cited by 37 · see citing works
Wolf, K., & Malinverni, R. (1999) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.43.6.1491 · Cited by 36 · see citing works
Gabel, B. R., Elwell, C. A., van IJzendoorn, S. C. D., et al. (2004) · Infection and Immunity · doi:10.1128/iai.72.12.7367-7373.2004 · Cited by 35 · see citing works
Beutler, A. M., Hudson, A. P., Whittum‐Hudson, J. A., et al. (1997) · JCR Journal of Clinical Rheumatology · doi:10.1097/00124743-199706000-00001 · Cited by 29 · see citing works
Self-citationChoong, J., Wyrick, P. B., Stuart, E. S., et al. (2021) · PubMed · doi:10.17615/qap3-zg62 · Cited by 25 · see citing works
A chlamydial major outer membrane protein extract as a trachoma vaccine candidate.
Campos, M., Pal, S., O’Brien, T. P., et al. (1995) · PubMed · Cited by 24 · see citing works
Prevention of pelvic inflammatory disease by the control ofC. trachomatisinfection
Honey, E. J., & Templeton, A. (2002) · International Journal of Gynecology & Obstetrics · doi:10.1016/s0020-7292(02)00185-6 · Cited by 18 · see citing works
Barry, A. L., Bryskier, A., Traczewski, M. M., et al. (2004) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2004.00759.x · Cited by 9 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [30]Gérard HC Whittum-Hudson JA Hudson AP C pneumoniae utilizes apoE and the LDL receptor family for host cell attachment 2006 Eleventh International Symposium on Human Chlamydial Infections Canada Niagara-on-the-Lake
- [31]Gérard HC Whittum-Hudson JA Hudson AP C pneumoniae utilizes apoE and the LDL receptor family for host cell attachment 2006 International Chlamydia Symposium San Francisco 153 156
Cited by
Sorted by citations
Polymeric materials with antimicrobial activity
Muñoz-Bonilla, A., & Fernández-García, M. (2012) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2011.08.005 · Cited by 1,221 · see citing works
Nanotechnology approaches for global infectious diseases
Kirtane, A. R., Verma, M., Karandikar, P., Furin, J., Langer, R., & Traverso, G. (2021) · Nature Nanotechnology · doi:10.1038/s41565-021-00866-8 · Cited by 520 · see citing works
Bacteria‐Responsive Multifunctional Nanogel for Targeted Antibiotic Delivery
Xiong, M., Li, Y., Bao, Y., Yang, X., Hu, B., & Wang, J. (2012) · Advanced Materials · doi:10.1002/adma.201202847 · Cited by 299 · see citing works
- Authors
- Toti, U. S., Guru, B. R., Hali, M., McPharlin, C. M., Wykes, S. M., Panyam, J., & Whittum-Hudson, J. A.
- Affiliations
- University of Minnesota (US)
- Wayne State University (US)
- Corresponding author
- Panyam, Jayanth
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 32
- Issue
- 27
- Pages
- 6606-6613
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3133877
- OpenAlex
- W1983435244
- Cited by
- 143
- References
- 34
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 10 · 2023: 11 · 2022: 9 · 2021: 16 · 2020: 5 · 2019: 15 · 2018: 9 · 2017: 10 · 2016: 10 · 2015: 7 · 2014: 11 · 2013: 2 · 2012: 8
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01AI080928)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- Chlamydia trachomatis, Chlamydia pneumoniae, PLGA nanoparticles, targeted antibiotic delivery, intracellular inclusions, persistent chlamydial infection, rifampicin, azithromycin, nanoparticle trafficking, combination antibiotic therapy
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Anti-Bacterial Agents, Cell Line, Chemistry, Pharmaceutical, Chlamydia Infections, Chlamydia trachomatis, Coumarins, Dose-Response Relationship, Drug, Drug Synergism, Humans, Microbial Sensitivity Tests, Polyglycolic Acid, Rifampin, Time Factors, Drug Delivery Systems, Azithromycin, Lactic Acid, Intracellular Space, Microbial Viability, Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
