Analgesic Efficacy and Safety of DALDA Peptide Analog Delivery to the Brain Using Oil-in-Water Nanoemulsion Formulation

作者：Shah Lipa; Kulkarni Praveen; Ferris Craig; Amiji Mansoor M^*

来源：Pharmaceutical Research, 2014, 31(10): 2724-2734.

DOI：10.1007/s11095-014-1370-y

• Blood-brain barrier
• DALDA analgesic peptide
• functional magnetic resonance imaging
• oil-in-water nanoemulsion

Purpose The main objective of this study was to develop and evaluate therapeutic efficacy and safety following systemic delivery of a peptide analgesic into the CNS using an oil-in-water nanoemulsion system.
Methods We have formulated a safe and effective, omega-3 rich polyunsaturated fatty acid containing oil-in-water nanoemulsion formulation, for encapsulating and delivering chemically-modified DALDA, a potent mu-opioid peptide analogue, to the CNS. One of the challenges with CNS delivery is the lack of a non-invasive bioanalytical technique to confirm CNS uptake and therapeutic efficacy. Using blood oxygen-level dependent (BOLD) functional magenetic resonance imaging (fMRI), we provide quantitative evidence of nanoemulsion-based delivery and analgesic activity of DALDA analogue in capsaicin-induced awake rat model of pain.
Results Nanoemulsion formulation effectively encapsulated the modified analgesic peptide and demonstrated efficacy in the capsaicin-pain induced functional magnetic resonance imaging model in rodents. Preliminary safety evaluations show that the nanoemulsion system was well tolerated and did not cause any acute negative effects.
Conclusions Overall, these results show tremendous opportunity for the development of modified peptide analgesic-encapsulated nanoemulsion formulations for CNS delivery and therapeutic efficacy.

• 出版日期2014-10
• 单位东北大学