Development of a nanoparticle-based system for the delivery of retinoic acid into macrophages
Abstract
The aim of the present work is to prepare nanoparticulate systems that can target and modulate the functions of mononuclear phagocytes by local administration. All-trans retinoic acid (RA) was chosen as an immunomodulator to be encapsulated in biodegradable nanoparticles (NP). Different formulations were prepared by the nanoprecipitation method and poly(d,l)lactic acid based nanocapsules (NC) were selected to continue the study. RA-NC demonstrated a sustained release profile and an enhanced stability for 7 days. The uptake of fluorescent (NileRed) labeled NP was conducted on bone marrow derived macrophages (BMM) in vitro and xenograft glioma nude mice in vivo. Fluorescent microscopy observations and flow cytometry analysis demonstrated that NR-NC were engulfed by BMM in vitro and lasted inside over 7 days. The intratumoral injection of NR-NC confirmed that NC were efficiently uptaken by infiltrated macrophages. The effects of RA loaded NC on BMM were also evaluated by RT(2)-PCR array. Our results suggest that polymeric nanoparticles are suitable carriers to deliver RA into macrophages and can offer a new strategy in tumor macrophage-based treatment.
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In physical entrapment, RA is captured during nanoparticle formation or in the pores of the nanoparticles.
“Concerning physical entrapment, RA is captured during nanoparticle formation57,58 or in the pores of the nanoparticles59.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [58]
RA formulations with an average diameter of 130-250 nm and an entrapment efficiency of ATRA between 2.3 and 310 μg per mg of nanoparticle have been developed.
“RA formulations with an average diameter of 130–250 nm58,74 and an entrapment efficiency of ATRA between 2.3 and 310 μg124 per mg of nanoparticle have been developed.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [58]
RA formulations are taken up by macrophages and induce anti-inflammatory responses by suppressing NF-kB signaling and increasing bone morphogenetic protein 2 signaling, as well as by enhancing the production of anti-inflammatory cytokines (e.g., IL-10).
“RA formulations are taken up by macrophages and induce anti-inflammatory responses by suppressing NF-kB signaling and increasing bone morphogenetic protein 2 signaling (pivotal for bone and cartilage development), as well as by enhancing the production of anti-inflammatory cytokines (e.g., IL-10)58,124.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [58]
In general, RA formulations showed sustained intracellular RA delivery for a few days.
“In general, RA formulations showed sustained intracellular RA delivery for a few days58,74.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [58]
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References 49 · Cited by 47
- Authors
- Almouazen, E., Bourgeois, S., Boussaïd, A., Valot, P., Malleval, C., Fessi, H., Nataf, S., & Briançon, S.
- Affiliations
- Lyon 1 Université (FR)
- Corresponding author
- Bourgeois, Sandrine
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 430
- Issue
- 1-2
- Pages
- 207-215
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W2091342503
- Cited by
- 47
- References
- 49
- Citations by year
- 2022: 1 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 8 · 2017: 7 · 2016: 4 · 2015: 7 · 2014: 2 · 2013: 2 · 2012: 1
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche
- 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
- retinoic acid, nanoparticle drug delivery, macrophages, biodegradable nanoparticles, nanoprecipitation, sustained drug release, bone marrow-derived macrophages, glioma, tumor-associated macrophages, immunomodulation, intratumoral injection, nanoparticle uptake
- MeSH terms
- Animals, Biological Transport, Brain Neoplasms, Chemistry, Pharmaceutical, Drug Carriers, Drug Compounding, Drug Stability, Female, Flow Cytometry, Fluorescent Dyes, Glioma, Humans, Immunologic Factors, Kinetics, Macrophages, Mice, Inbred C57BL, Mice, Nude, Microscopy, Fluorescence, Oxazines, Phagocytosis, Polyesters, Polymers, Chemical Precipitation, RNA, Messenger, Solubility, Technology, Pharmaceutical, Tretinoin, Injections, Intralesional, Cytokines, Lactic Acid, Reverse Transcriptase Polymerase Chain Reaction, Xenograft Model Antitumor Assays, Nanotechnology, Cell Line, Tumor, Mice, Nanocapsules
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