Imine bond formation: A novel concept to incorporate peptide drugs in self-emulsifying drug delivery systems (SEDDS)

Abstract

Hypothesis: Because of its hydrophilic character the peptide drug Polymyxin B (PMB) cannot be incorporated in lipophilic nanocarrier systems such as self-emulsifying drug delivery systems (SEDDS) for oral administration. Due to the formation of imine conjugates between the primary amino groups of PMB and the carbonyl group of cinnamaldehyde, however, drug lipophilicity might be sufficiently raised for incorporation in SEDDS.

Methods: Imine bonds were formed between the primary amino groups of PMB and the carbonyl group of cinnamaldehyde. PMB-cinnamaldehyde conjugate was characterized regarding degree of substitution, log P and release of PMB due to interaction with bovine serum albumin (BSA), SEDDS loading and cell viability.

Results: 87.1% of primary amines formed imines with cinnamaldehyde. Log P was increased 69.183 - folds. BSA triggered release of PMB was 45.2%, 64.9% and 80.6% within 16 h. Log D_{SEDDS/Release medium} of PMB-cinnamaldehyde conjugate was 3.4.

Conclusion: According to these findings, the concept of imine bond formation with cinnamaldehyde can be considered as a novel concept for increasing lipophilicity of the hydrophilic antibiotic peptide PMB.

Keywords: Bovine serum albumin; Cinnamaldehyde; Nanocarriers; Oral drug delivery; Polymyxin B; SEDDS; Self-emulsifying drug delivery systems.