Bi-Botti C. Youan

Evaluation of sucrose esters as alternative surfactants in microencapsulation of proteins by the solvent evaporation method

Sucrose esters (SE) are surfactants with potential pharmaceutical applications because of their low toxicity, biocompatibility, and excellent biodegradability. The objective of the study was to investigate SE as alternative surfactants in stabilizing emulsions for the preparation of protein-loaded microparticles. To achieve this goal, using bovine serum albumin as model protein and 75/25 poly(d,1-lactide-co-glycolide) as polymer carrier, we have investigated the influence of the following formulation variables on particle characteristics: (1) SE concentration from 0.01% to 1% (wt/vol), (2) hydrophile-lipophile balance (HLB) value of SE from 6 to 15, and (3) the nature of emulsion stabilizer. The formulations were characterized using ATR-FTIR spectroscopy, bicinchoninic acid protein assay, optical microscopy and SDS-PAGE. Results showed that at 0.05% (wt/vol) surfactant concentration, SE with HLB of 6 to 15 provided discrete and spherical microparticles with the highest encapsulation efficiency compared with controls polyvinyl alcohol (PVA) and poloxamer 188. These results may be explained by the difference in critical micelle concentration, diffusion, and partition coefficient among the tested surfactants. HLB values were consistent with SE spectral data. The protein molecular weight was preserved after the encapsulation process. The effective SE concentration was far less (20-to 200-fold) than that is usually required for PVA in microencapsulation of proteins. However, the encapsulation efficiency was relatively lower (∼13.5%). These preliminary results suggest that it may be desirable to optimize such formulations in vitro and in vivo for SE to be eventually used as altermative surfactants in the development of microparticulate systems for parenteral delivery of protein and gene medicines.

Oral delivery of low-molecular-weight heparin using sodium caprate as absorption enhancer reaches therapeutic levels

RETRACTED

Zonula occludens toxin synthetic peptide derivative AT1002 enhances in vitro and in vivo intestinal absorption of low molecular weight heparin.

RETRACTED

Modulation of gastrointestinal permeability of low‐molecular‐weight heparin by L‐arginine: in‐vivo and in‐vitro evaluation

L‐Arginine is the principal physiological precursor of nitric oxide (NO, a key neurotransmitter) that plays a versatile role in the physiology of the gastrointestinal tract. In this study, the efficacy of L‐arginine in enhancing intestinal absorption of ardeparin, a low‐molecular‐weight heparin (LMWH) was investigated in Caco‐2 cell monolayers and a rat model. Regional permeability studies using rat intestine were performed using a modified Ussing chamber. Cell viability in the presence of various concentrations of enhancer was determined by MTT assay. Furthermore, the eventual mucosal epithelial damage was histologically evaluated. LMWH formulated with L‐arginine was administered orally to male Sprague‐Dawley rats and the absorption of LMWH was determined by measuring plasma anti‐factor Xa activity. Higher ardeparin in‐vitro permeability (∼3 fold) compared with control was observed in the presence of 2% L‐arginine. Regional permeability studies indicated predominant absorption in the colon region. Cell viability studies showed no significant cytotoxicity below 0.8% L‐arginine. The oral bioavailability of ardeparin formulated with L‐arginine (250 mg kg−1) was increased by ∼2 fold compared with control. The formulation was well tolerated by the rats and no abnormal histopathological findings were observed in intestinal tissues of rats exposed to L‐arginine. These results suggest that L‐arginine may be useful in enhancing the intestinal absorption of LMWHs.

Microencapsulation of Superoxide Dismutase into Biodegradable Microparticles by Spray-Drying

The aim of this work was to encapsulate superoxide dismutase (SOD) into biodegradable microparticles by spray-drying technique. The nature of the organic solvent to dissolve the polymer, the method of incorporation of the drug in the organic phase (with or without a surfactant, namely sucrose ester of HLB = 6), the surfactant/polymer ratio, and the nature of the biodegradable polyesters were investigated as formulation variables. The polyesters investigated as matrix were poly(ε-caprolactone) (PCL), poly(d, l, lactide-co-glycolide) (PLG-RG756), and poly(d, l-lactide) (PLA-R207) of respective molecular weight 78.2 kDa, 84.8 kDa, and 199.8 kDa. At surfactant/polymer ratio of 1/10, the SOD-retained enzymatic activities were higher (>95%) for PLG-RG756 and PLA-R207 but relatively lower for the PCL (∼ 85%) probably due to the PCL relatively higher hydrophobicity. The obtained microparticles exhibited average volume mean diameter of 4–10 μ m, the smaller for PCL and the larger for PLG-RG756 polymeric matrix. The in vitro release profile showed that SOD was completely (100%) released from PLA-R207 in 48 hr and from PLG-RG756 and PCL within 72 hr. These results showed that spray-drying with incorporation of surfactant such as sucrose ester may efficiently encapsulate SOD into biodegradable microparticles. Such formulations may improve the bioavailability of SOD and similar biopharmaceuticals.

Microencapsulation of Superoxide Dismutase into Poly(ε-Caprolactone) Microparticles by Reverse Micelle Solvent Evaporation

The aim of this work was to encapsulate superoxide dismutase (SOD) in poly(ε-caprolactone) (PCL) microparticles by reverse micelle solvent evaporation. The concentration of PCL, the hydrophile-lipophile balance (HLB), and concentration of the sucrose ester used as surfactant in the organic phase were investigated as formulation variables. Relatively higher encapsulation efficiency (∼48%) and retained enzymatic activity (>90%) were obtained with microparticle formulation made from the 20% (w/v) PCL and 0.05% (w/v) sucrose ester of HLB = 6. This formulation allowed the in vitro release of SOD for at least 72 hr. These results showed that reverse micelle solvent evaporation can be used to efficiently encapsulate SOD in PCL microparticles. Such formulations may improve the bioavailability of SOD.