An HPLC Method for Microanalysis and Pharmacokinetics of Marine Sulfated Polysaccharide PSS-Loaded Poly Lactic-co-Glycolic Acid (PLGA) Nanoparticles in Rat Plasma

Abstract

This study was aimed at developing a sensitive and selective HPLC method with postcolumn fluorescence derivatization for the detection of propylene glycol alginate sodium sulfate (PSS) in rat plasma. Plasma samples were prepared by a simple and fast ultrafiltration method. PSS was extracted from rat plasma with d-glucuronic acid as internal standard. Isocratic chromatographic separation was performed on a TSKgel G2500 PWxL column with the mobile phase of 0.1 M sodium sulfate at a flow rate of 0.5 mL/min. Analyte detection was achieved by fluorescence detection (FLD) at 250 nm (excitation) and 435 nm (emission) using guanidine hydrochloride as postcolumn derivatizing reagent in an alkaline medium at 120 °C. The calibration curve was linear over a concentration range of 1–500 μg/mL, and the lower limit of detection (LLOD) was found to be 250 ng/mL. This validated method was applied successfully to the pharmacokinetic study of PSS and PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (PSS-NP) in rat plasma after a single intravenous (PSS only) and oral administration (PSS and PSS-NP). Significant differences in the main pharmacokinetic parameters of PSS and PSS-NP were observed. The relative bioavailability of PSS-NP was 190.10% compared with PSS which shows that PSS-NP can improve oral bioavailability.

Drug delivery for bioactive polysaccharides to improve their drug-like properties and curative efficacy

“…The average size of PSSNPs was 182 nm (PDI, 0.012), the entrapment rate was 75.8%, and the drug loading rate was 10.8%. Following oral administration to rats, PSS-NPs not only extended the residence time of PSS in the blood, but also significantly improved the relative bioavailability (190.1%) compared to the PSS solution (Li et al, 2013). The contributing factors might include absorption in the form of NPs, concentrated PSS levels in absorption sites, and/or sustained release of PSS from the NPs.…”

“…Since an HPGPC (high performance gel permeation chromatography) method with postcolumn fluorescence derivatization was used, the PS itself rather than its degradation products was determined. In another study, a 9.54% bioavailability was reported on a marine sulfated PS (11 kDa) after oral administration of 50 mg/kg to rats, which was also determined by the same HPGPC methodology (Li et al, 2013).…”

“…4)-linked dextran backbone with a (1 ! 6)-linked branch every 10 residues; MW, 20.7 kDa (Niu et al, 2011) Liposome (in vitro; SC): improved immunoregulatory activities and adjuvanticity (Fan et al, 2011(Fan et al, , 2013a) ISFS (poloxamer-based): week-long sustained release; improved administration compliance (Yu et al, 2017) Lycium barbarum PSs A neutral heteroglycan composed of glucose, xylose, galactose, rhamnose, and mannose (49.8:31.3:9.3:7.5:6.4, molar ratio); MW, 24-241 kDa (Amagase et al, 2009;Wu et al, 2010) Liposome (in vitro; SC): improved immunoregulatory activities and adjuvanticity (Bo et al, 2015 Rehmannia glutinosa PS An acidic PS composed of L-arabinose, D-galactose, Lrhamnose, and D-galacturonic acid (10:10:1:1 or 14:7:3:8, molar ratio); MW, 35.7 kDa (Tomoda et al, 1994;Tan et al, 2012) Liposome (in vitro; SC): improved immunoregulatory activities and adjuvanticity (Huang et al, 2014 Epimedium PS An acidic PS composed of xylose, galactose, rhamnose, arabinose, and galacturonic acid (6.4:2.3:1.8:6.9:82.6, weight ratio); MW, 1.46 kDa (Li, 2005) Liposome (in vitro): improved immunoregulatory activities; synergistic effects with propolis flavone (Fan et al, 2013b(Fan et al, , 2015b Propylene glycol alginate sodium sulfate (Li et al, 2013) A marine sulfated PS composed of b-D-mannuronic acid and a-L-guluronic acid; MW, 11 kDa (PDI, 1.6) IV: t 1/2 , 3.11 h; MRT, 2.59 h. Oral BA: 9.54% (rats)…”

HPLC Method for Microanalysis and Pharmacokinetics of Marine Sulfated Polysaccharides, Propylene Glycol Alginate Sodium Sulfate

“…In 2013, Li et al (2013) carried out the ultrafiltration method to remove protein of PSS blood samples, laying the foundation of polysaccharide pharmacokinetics. In the pretreatment procedure, PSS was released completely from the blood plasma and almost all plasma proteins were retained in Ultra-0.5 centrifugal filter (30 kDa, MWCO).…”

“…Sun et al (2012) selected guanidine as a fluorometric reagent for the determination of oligosaccharide HS203 in beagle dog blood plasma by HPLC post-column fluorescence derivatization method. In 2013, Li et al (2013) also chose guanidine hydrochloride as a post-column derivatizing reagent to detect PSS in rat plasma by HPLC method.…”