ABSTRACT
The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide—arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2 ± 7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17 ± 1.88) %, an encapsulation rate (5.85 ± 0.72) %, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.
ABSTRACT
The mucous barrier is a major physiological obstacle that the mucosal drug delivery system needs to deal with. In response to this physiological barrier, many achievements have been made in research of mucosal adhesion and mucus penetration. This review puts emphasis on the progress of the research on new mucosal adhesion strategies such as cationization, sulfhydrylization, maleimide functionalization, lectinization and catechol conjugation; polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly (2-alkyl-2-oxazoline) (POZ), zwitterionic polymers and other mucus-inert materials, strategies to enhance mucus penetration ability such as enzyme functionalization, reducing agent pretreatment and so on. The problems of each strategy are also analyzed and discussed, which can provide some references for clinical transformation.
ABSTRACT
OBJECTIVE: To develop a method for determination of the contents and related substances in nevirapine zidovudine and lamivudine tablets. METHODS: The samples were separated on a Welch Ultimate AQ-C18 (4.6 mm × 250 mm, 5 μm) column by gradient elution using acetonitrile-methanol-0.025 mol·L-1 ammonium acetate solution (pH 4.0) as the mobile phase at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 277 nm, and the column temperature was 30°C. RESULTS: Nevirapine, lamivudine, and zidovudine had good liner relationship in the range of 10.3 - 310.9, 7.9 - 237.1, and 14.9 - 449.6 μg·mL-1, respectively. The correlation coefficients were all more than 0.9998. The average recoveries were 100.6% (RSD 0.4%), 100.0%(RSD 0.7%), and 100.2% (RSD 0.6%), respectively. Complete separation was achieved for the related substances (lamivudine acid, lamivudine related compound B, uracil, cytosine, thymine, nevirapine related compound A, and nevirapine related compound B). Cytosine, uracil, and thymine had good liner relationship in the range of 76.8 - 1152, 76.8 - 1152, and 744-14880 ng·mL-1, respectively. The correlation coefficients were all more than 0.9991. The average recoveries were 101.5% (RSD 4.8%), 102.8% (RSD 4.2%), and 101.2% (RSD 1.2%), respectively. CONCLUSION: The method is rapid, simple, and accurate with good reproducibility. It can be used for the quality control of nevirapine zidovudine and lamivudine tablets.