IADR Abstract Archives
Enhanced cellular absorption of acyclovir with solid lipid nanoparticles
Objectives: Acyclovir, a potential anti-viral drug for oral herpes infection, has lower permeability into the cells due to its hydrophobic nature, leading to its bioavailability is 15-30% and a half-life of 3h. Encapsulation of acyclovir into nanocarriers, such as solid lipid nanoparticles (SLN), has provided a sustained release of the drug for 24h. The following study works with the in vitro drug transport model to observe the acyclovir (ACY) permeation encapsulated in SLN (ACY-SLN).
Methods: Human oral keratinocytes seeded in 12 well-plate inserts were treated with 1mg/ml ACY in ACY-SLN. Treatment with only 1mg/ml of ACY and stearic acid nanoparticles (STA) was used as a control (n=3). Absorbance reading followed by transmission electron microscopy was done of the collected media at different time points after 24h of treatment. Gene expressions of the tight junction proteins, such as epithelial cadherin (ECAD), Tight Junction Protein -1 (TJP-1), occludin (OCLN), claudin (CLDN1), were obtained by real-time PCR analysis of the lysed cells after 48h of treatment. Statistical analyses were performed using paired T-test and one-way ANOVA with post-hoc Bonferroni test with global significant level pre-set at 5% for intra- and inter-group analysis, respectively.
Results: A higher permeation of acyclovir was recorded in the basolateral chamber when cells were exposed to ACY through absorbance reading. TEM images reveal the presence of STA and ACY-SLN in the basolateral chamber after 8h and 24h of exposure. A significant decrease in the concentration of ACY from 298±3µg/ml at 0h to 114±3µg/ml at 48h in the apical was observed for ACY-SLN, compared to other groups. A 10-fold increase in the gene expression of CLDN1 was noted when the cells were treated with STA and ACY-SLN.
Conclusions: Stearic acid acts as transcellular permeation enhancer, improving acyclovir's permeability into the cells with a sustained release of the drug into the basolateral chamber.
Methods: Human oral keratinocytes seeded in 12 well-plate inserts were treated with 1mg/ml ACY in ACY-SLN. Treatment with only 1mg/ml of ACY and stearic acid nanoparticles (STA) was used as a control (n=3). Absorbance reading followed by transmission electron microscopy was done of the collected media at different time points after 24h of treatment. Gene expressions of the tight junction proteins, such as epithelial cadherin (ECAD), Tight Junction Protein -1 (TJP-1), occludin (OCLN), claudin (CLDN1), were obtained by real-time PCR analysis of the lysed cells after 48h of treatment. Statistical analyses were performed using paired T-test and one-way ANOVA with post-hoc Bonferroni test with global significant level pre-set at 5% for intra- and inter-group analysis, respectively.
Results: A higher permeation of acyclovir was recorded in the basolateral chamber when cells were exposed to ACY through absorbance reading. TEM images reveal the presence of STA and ACY-SLN in the basolateral chamber after 8h and 24h of exposure. A significant decrease in the concentration of ACY from 298±3µg/ml at 0h to 114±3µg/ml at 48h in the apical was observed for ACY-SLN, compared to other groups. A 10-fold increase in the gene expression of CLDN1 was noted when the cells were treated with STA and ACY-SLN.
Conclusions: Stearic acid acts as transcellular permeation enhancer, improving acyclovir's permeability into the cells with a sustained release of the drug into the basolateral chamber.