Abstract
PEGylated Eudragit L100 (ELP)-containing proliponiosomes (PLNs) were developed for improved oral delivery of celecoxib (CXB). The successful introduction of PEG 2000 or 5000 to Eudragit L100 (EL) was confirmed via proton nuclear magnetic resonance analysis of which calculated molar substitution ratio of PEG to EL was 36.0 or 36.7, respectively. CXB, ELP, phospholipid, and non-ionic surfactants were dissolved in dimethyl sulfoxide and lyophilized to produce CXB-loaded PLNs (CXB@PLNs). The physical state of CXB@PLNs was evaluated using differential scanning calorimetry and powder X-ray diffractometry, which revealed that crystalline CXB was transformed into amorphous form after the fabrication procedure. The reconstitution of CXB@PLNs in aqueous media generated CXB-loaded liponiosomes with nano-sized mean diameters and spherical morphology. CXB@PLNs displayed enhanced dissolution rate and permeability compared to CXB suspension. In vivo pharmacokinetic studies performed on rats demonstrated the improved oral bioavailability of CXB@PLNs compared to that of CXB suspension. No serious systemic toxicity was observed in the blood biochemistry tests performed on rats. These results suggest that the developed PLNs could be promising oral delivery systems for improving the bioavailability of poorly water-soluble drugs, such as CXB.
Highlights
Celecoxib (CXB) is a nonsteroidal anti-inflammatory drug (NSAID) indicated for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute pain, primary dysmenorrhea, and familial adenomatous polyposis [1,2]
PEG 1000, aminefunctionalized methoxy PEGs, N-hydroxysuccinimide (NHS), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), trimethylamine (TEA), sodium dodecyl sulfate (SDS), Solutol HS 15 (SHS), tween 80, 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES), Hank’s balanced salt solution (HBSS), sodium bicarbonate, and d-glucose were purchased from Sigma–Aldrich
Our preliminary study revealed that ELP2k and ELP5k dispersions in deionized water (DDW) exhibited mean diameters of 49.4 ± 28.0 nm (PDI: 1)
Summary
Celecoxib (CXB) is a nonsteroidal anti-inflammatory drug (NSAID) indicated for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute pain, primary dysmenorrhea, and familial adenomatous polyposis [1,2]. Its poor solubility in aqueous media (1.4 and 1.2 μg/mL at pH 1.2 and 6.8, respectively) causes limited and highly variable oral absorption [2], which compromises its therapeutic efficacy [4]. To address this issue, Celebrex, a commercially available CXB product, contains sodium dodecyl sulfate (SDS) as a solubilizer. Celebrex, a commercially available CXB product, contains sodium dodecyl sulfate (SDS) as a solubilizer This anionic surfactant is well-known for its high drug solubilizing potential with the characteristic micelle-forming property [5], several toxicity concerns have always been disputed, such as skin and mucosal irritations [6]. These strategies can be categorized into mainly two types: amorphization [6,7,8] and nanonization [9,10,11]
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