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Synthesis and Characterization of Placental Chondroitin Sulfate A plCSA-Targeting Lipid-Polymer Nanoparticles
Published on: September 18, 2018
Folate decorated chitosan-chondroitin sulfate nanoparticles loaded hydrogel for targeting macrophages against
Bazla Siddiqui1, Asim Ur Rehman1, Rabia Gul2
1Department of Pharmacy, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
Abstract:
Inflammatory cell infiltration, particularly macrophages, plays a major contribution to the pathogenesis of Rheumatoid Arthritis (RA). Exploiting the overexpression of folate receptors (FR-β) on these recruited macrophages has gained significant attraction for ligand-targeted delivery. Leflunomide (LEF), being an immunomodulatory agent is considered the cornerstone of the therapy, however, its oral efficacy is impeded by low solubility and escalating adverse effects profile. Therefore, in the present work, we developed Folate-conjugated chitosan-chondroitin sulfate nanoparticles encapsulating LEF for selective targeting at inflammatory sites in RA. For this purpose, the folate group was first conjugated with the chitosan polymer. After which, Folate Leflunomide Nanoparticles (FA-LEF-NPs) were synthesized through the ionotropic gelation method by employing FA-CHI and CHS. The polymers CHI and CHS were also presented with innate anti-inflammatory and anti-rheumatic attributes that were helpful in provision of synergistic effects to the formulation. These nanoparticles were further fabricated into a hydrogel, employing almond oil (A.O) as a permeation enhancer. The in vivo studies justified the preferential accumulation of FA-conjugated nanoparticles at inflamed joints more than any other organ in comparison to the free LEF and LEF-NPs formulation. The FA-LEF-NPs loaded hydrogel also ascertained a minimal adverse effect profile with an improvement of inflammatory cytokines expression.
Insights
Targeted nanoparticles deliver leflunomide (LEF) to Rheumatoid Arthritis (RA) inflammation sites, improving efficacy and reducing side effects. Folate-conjugated nanoparticles show preferential accumulation in inflamed joints.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Rheumatology
Background:
- Rheumatoid Arthritis (RA) pathogenesis involves inflammatory cell infiltration, particularly macrophages.
- Folate receptors (FR-β) are overexpressed on macrophages, presenting a target for drug delivery in RA.
- Leflunomide (LEF) is a key RA therapy, but its oral use is limited by poor solubility and side effects.
Purpose of the Study:
- To develop folate-conjugated chitosan-chondroitin sulfate nanoparticles encapsulating LEF for targeted delivery to RA inflammatory sites.
- To create a hydrogel formulation of these nanoparticles using almond oil as a permeation enhancer.
- To evaluate the in vivo biodistribution, efficacy, and safety profile of the developed formulation.
Main Methods:
- Folate conjugation to chitosan polymer.
- Synthesis of folate- Leflunomide nanoparticles (FA-LEF-NPs) via ionotropic gelation using folate-chitosan and chondroitin sulfate.
- Fabrication of FA-LEF-NPs into a hydrogel with almond oil.
- In vivo studies to assess nanoparticle accumulation and therapeutic effects.
Main Results:
- FA-LEF-NPs demonstrated preferential accumulation at inflamed joints compared to free LEF and non-conjugated LEF-NPs.
- The hydrogel formulation exhibited a minimal adverse effect profile.
- Significant improvement in inflammatory cytokine expression was observed with the FA-LEF-NPs loaded hydrogel.
Conclusions:
- Folate-conjugated nanoparticles offer a promising strategy for targeted delivery of LEF in Rheumatoid Arthritis.
- The developed nanoparticle-hydrogel system enhances therapeutic efficacy while minimizing adverse effects.
- This approach holds potential for improved management of inflammatory conditions like RA.
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