Development of nanoparticulate drug delivery systems for mucosal drug delivery

To ensure effectiveness of mucosal drug delivery, drugs molecules have to diffuse across mucus layer. Although parenteral routes provide good absorption, the invasiveness reduces patient compliance and emphasizes the need for alternative mucosal delivery strategies. On one hand, this study aimed to develop potential polymer-based nanoparticles (NPs) containing preactivated thiomers as excipients to enhance efficacy in mucosal delivery. Calcein, a hydrophilic molecule was used as the model drug. Calcein-loaded PAA250 NPs, highly reactive preactivated thiomer NPs (PAA250-Cys-MNA NPs), and less reactive preactivated thiomer (PAA250-Cys-NAC NPs) were prepared by ionic gelation method. The particle size, polydispersity index, and zeta potential of the calcein-loaded polymer-based NPs ranged from 180 to 190 nm, below 0.2, and -28 to -33 mV, respectively. The entrapment efficiency was found to be 6–10 %. All formulations remained stable for 7 days of storage. Results from penetration depth study showed that PAA250-Cys-NAC NPs were able to penetrate 1.2 times deeper into the mucus than PAA250-Cys-MNA NPs, and 2.2 times deeper than PAA250-NPs. In addition, the amount of calcein delivered across the mucus layer was 1.25- and 1.8-fold higher compared to PAA250-Cys-MNA NPs and PAA250 NPs, respectively. On the other hand, lipid nanocapsules (LNCs) were also developed and characterized for their potential in mucosal delivery. Curcumin loaded–LNCs (CCM–LNCs) were prepared by phase inversion temperature (PIT) method. Particle characteristics, morphology, entrapment efficiency (EE), and loading capacity were determined. Mucopenetration studies were conducted by Transwell® plate and tube methods. CCM solution was served as control. Particle size and zeta-potential of the CCM-loaded LNCs were 67.47 ± 0.15 nm and -32.86 ± 2.51 mV. EE and loading capacity of CCM–LNCs were found to be 98.38 ± 0.45% and 42.24 ± 2.24%, respectively. No significant changes on stability of CCM–LNCs was found after 30 days storage. CCM–LNCs could penetrate mucus 3 times deeper than CCM solution. Moreover, the delivered amount of CCM across the mucus layer was 6-fold higher compared with CCM solution. In conclusion, both preactivated thiomer NPs and LNCs with a negative charge demonstrated potential for delivering drugs across mucus layers. Highly reactive PAA250-Cys-MNA could be used as an excipient to enhance drug delivery across thin mucus layers, while less reactive PAA250-Cys-NAC NPs were suitable for delivering hydrophilic drugs across thick mucus layers. In addition, LNCs offered a promising particulate delivery system for lipophilic drugs across mucus.On the other hand, lipid nanocapsules (LNCs) were also developed and characterized for their potential in mucosal delivery. Curcumin loaded–LNCs (CCM–LNCs) were prepared by phase inversion temperature (PIT) method. Particle characteristics, morphology, entrapment efficiency (EE), and loading capacity were determined. Mucopenetration studies were conducted by Transwell® plate and tube methods. CCM solution was served as control. Particle size and zeta-potential of the CCM-loaded LNCs were 67.47 ± 0.15 nm and -32.86 ± 2.51 mV. EE and loading capacity of CCM–LNCs were found to be 98.38 ± 0.45% and 42.24 ± 2.24%, respectively. No significant changes on stability of CCM–LNCs was found after 30 days storage. CCM–LNCs could penetrate mucus 3 times deeper than CCM solution. Moreover, the delivered amount of CCM across the mucus layer was 6-fold higher compared with CCM solution.In conclusion, both preactivated thiomer NPs and LNCs with a negative charge demonstrated potential for delivering drugs across mucus layers. Highly reactive PAA250-Cys-MNA could be used as an excipient to enhance drug delivery across thin mucus layers, while less reactive PAA250-Cys-NAC NPs were suitable for delivering hydrophilic drugs across thick mucus layers. In addition, LNCs offered a promising particulate delivery system for lipophilic drugs across mucus.