Formulation and characterisation of liposomes loaded with a model small nucleic acid for nasal delivery
Cristina Rey Blanes1 & Reanne Beaird1, Mira Buhecha1, Eleni Axioti1, William Terrell1, Nektaria Karavas2, Mohammad Isreb3, Robert Price1, Jagdeep Shur1 & Irene Rossi1
1Nanopharm, An Aptar Pharma Company, Grange Road, Cwmbran, NP44 3WY, United Kingdom
2Aptar Pharma, Congers, New York, 10920, United States
3University of Bradford, Faculty of Life Sciences, School of Pharmacy and Medical Sciences, Richmond Road, Bradford, BD7 1DP, United Kingdom
Summary
Nucleic acid delivery for vaccination and other applications (i.e. anti-cancer therapy, cystic fibrosis) has currently attracted a lot of interest. However, nucleic acids can be susceptible to degradation and present some challenges, requiring an effective delivery platform. Liposomes have been used as a delivery system to entrap hydrophilic and hydrophobic drugs and nucleic acids preventing degradation, increasing absorption, allowing for a sustained release and acting as multifunctional vaccine adjuvant-delivery system. In this study, a liposomal suspension loaded with a model small deoxyribonucleic acid (DNA) was successfully developed and characterised for nasal delivery. Empty and DNA loaded liposomes were successfully manufactured and formulated for nasal delivery. pH (~ 6) and osmolality (~ 300 mOsm/kg) of the resulting formulations were suitable for the nose. Droplet size distribution of the spray emitted from Aptar CPS nasal pump was in the range for nasal deposition (30-120 µm), even though much closer to the upper limit. A potential reduction of the amount of the trimethyl chitosan (TMC) may help in obtaining smaller droplets, which will potentially increase the deposition at the target region (i.e. NALT and turbinates). Hydrodynamic diameter was larger for the DNA loaded liposomes (600 nm) than for empty ones, perhaps due to DNA conjugation or absorption to the external liposomal structure and/or DNA induced liposome-liposome fusion. The formulation’s positive charge determined by the presence of TMC, possibly covering liposomes surface, can allow to ionic interaction with the negatively charged mucin. Finally, liposomal structure and size was preserved after spraying as confirmed by dynamic light scattering and delivered drug assessment.
Key Message
Formulation and characterisation of liposomes loaded with a model small nucleic acid for nasal delivery
Cristina Rey Blanes1 & Reanne Beaird1, Mira Buhecha1, Eleni Axioti1, William Terrell1, Nektaria Karavas2, Mohammad Isreb3, Robert Price1, Jagdeep Shur1 & Irene Rossi1
1Nanopharm, An Aptar Pharma Company, Grange Road, Cwmbran, NP44 3WY, United Kingdom
2Aptar Pharma, Congers, New York, 10920, United States
3University of Bradford, Faculty of Life Sciences, School of Pharmacy and Medical Sciences, Richmond Road, Bradford, BD7 1DP, United Kingdom
Summary
Nucleic acid delivery for vaccination and other applications (i.e. anti-cancer therapy, cystic fibrosis) has currently attracted a lot of interest. However, nucleic acids can be susceptible to degradation and present some challenges, requiring an effective delivery platform. Liposomes have been used as a delivery system to entrap hydrophilic and hydrophobic drugs and nucleic acids preventing degradation, increasing absorption, allowing for a sustained release and acting as multifunctional vaccine adjuvant-delivery system. In this study, a liposomal suspension loaded with a model small deoxyribonucleic acid (DNA) was successfully developed and characterised for nasal delivery. Empty and DNA loaded liposomes were successfully manufactured and formulated for nasal delivery. pH (~ 6) and osmolality (~ 300 mOsm/kg) of the resulting formulations were suitable for the nose. Droplet size distribution of the spray emitted from Aptar CPS nasal pump was in the range for nasal deposition (30-120 µm), even though much closer to the upper limit. A potential reduction of the amount of the trimethyl chitosan (TMC) may help in obtaining smaller droplets, which will potentially increase the deposition at the target region (i.e. NALT and turbinates). Hydrodynamic diameter was larger for the DNA loaded liposomes (600 nm) than for empty ones, perhaps due to DNA conjugation or absorption to the external liposomal structure and/or DNA induced liposome-liposome fusion. The formulation’s positive charge determined by the presence of TMC, possibly covering liposomes surface, can allow to ionic interaction with the negatively charged mucin. Finally, liposomal structure and size was preserved after spraying as confirmed by dynamic light scattering and delivered drug assessment.
Key Message
A liposomal suspension loaded with a model small DNA was formulated for nasal delivery. In vitro assessment showed suitable characteristics for nasal delivery: pH, osmolality and droplet distribution when loaded into Aptar CPS pump. Finally, liposomal structure and size was preserved after spraying.