Abstract Title

Subcutaneous Injection of In Situ Self-assembly Nanoparticle to Encapsulate Lopinavir and Ritonavir

Presenter Name

Irin Tanaudommongkon

RAD Assignment Number

2000

Abstract

Purpose: Lopinavir (LPV) is one of the potent protease inhibitors (PI) that is used for the treatment of human immunodeficiency virus (HIV) infection. However, LPV has poor bioavailability when it is administered orally due to undergoing first-pass metabolism by hepatic cytochrome P450 (CYP) 3A4 isoenzyme, therefore LPV is a coformulated combination with ritonavir (RTV), another PI, to inhibit CYP3A4. Despite this advantage, oral LPV/RTV pill does not address non-adherence issues and gastrointestinal side (GI) effects. Long-acting injectable nanoformulations offers alternative therapeutic options for the treatment of HIV. Injectable nanoparticle has the potential to improve the pharmacokinetic properties of drug molecules, overcome GI side effects, and bypass first pass metabolism. The goal of this study was to develop a novel long-acting injectable nanoformulation to encapsulate LPV and RTV by using the in situ self-assembly nanoparticle (ISNP).

Methods: The preparation of LPV/RTV ISNPs was performed by the ISNP nanotechnology. The drug loading, drug entrapment efficiency and in-vitro release of NPs were measured by using HPLC. Particle size was determined by using a particle size analyzer. Rats were treated with 100 µl of LPV/RTV ISNPs to provide 100 mg/kg of LPV by subcutaneous injection. Then, blood was collected at predetermined time points. LPV and RTV concentrations in the plasma of rats were determined by LC-MS.

Results: LPV/RTV ISNPs were 167.8 nm with a narrow distribution of P.I. 98% for both RTV and LPV. The drug loadings were 23.5% for LPV and 5.9% for RTV. LPV and RTV exhibited sustained release profiles. Slow release rate of LPV was observed at about 20% on day 5 and followed by the sustained release beyond 14 days. RTV releases faster than LPV in the first 5 days and slower afterward when compared to LPV. LPV Ctrough in plasma remained above 160 ng/ml, and RTV Ctrough was about 50 ng/ml with one subcutaneous (subQ) injection in rats for 6 days.

Conclusions: We successfully prepared LPV/RTV ISNPs as lipid-based long-acting injection by using the ISNP nanotechnology. LPV/RTV ISNPs exhibited a sustained release behavior in both in-vivo and in-vitro studies.

Research Area

Pharmaceutical Sciences

Presentation Type

Poster

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Subcutaneous Injection of In Situ Self-assembly Nanoparticle to Encapsulate Lopinavir and Ritonavir

Purpose: Lopinavir (LPV) is one of the potent protease inhibitors (PI) that is used for the treatment of human immunodeficiency virus (HIV) infection. However, LPV has poor bioavailability when it is administered orally due to undergoing first-pass metabolism by hepatic cytochrome P450 (CYP) 3A4 isoenzyme, therefore LPV is a coformulated combination with ritonavir (RTV), another PI, to inhibit CYP3A4. Despite this advantage, oral LPV/RTV pill does not address non-adherence issues and gastrointestinal side (GI) effects. Long-acting injectable nanoformulations offers alternative therapeutic options for the treatment of HIV. Injectable nanoparticle has the potential to improve the pharmacokinetic properties of drug molecules, overcome GI side effects, and bypass first pass metabolism. The goal of this study was to develop a novel long-acting injectable nanoformulation to encapsulate LPV and RTV by using the in situ self-assembly nanoparticle (ISNP).

Methods: The preparation of LPV/RTV ISNPs was performed by the ISNP nanotechnology. The drug loading, drug entrapment efficiency and in-vitro release of NPs were measured by using HPLC. Particle size was determined by using a particle size analyzer. Rats were treated with 100 µl of LPV/RTV ISNPs to provide 100 mg/kg of LPV by subcutaneous injection. Then, blood was collected at predetermined time points. LPV and RTV concentrations in the plasma of rats were determined by LC-MS.

Results: LPV/RTV ISNPs were 167.8 nm with a narrow distribution of P.I. 98% for both RTV and LPV. The drug loadings were 23.5% for LPV and 5.9% for RTV. LPV and RTV exhibited sustained release profiles. Slow release rate of LPV was observed at about 20% on day 5 and followed by the sustained release beyond 14 days. RTV releases faster than LPV in the first 5 days and slower afterward when compared to LPV. LPV Ctrough in plasma remained above 160 ng/ml, and RTV Ctrough was about 50 ng/ml with one subcutaneous (subQ) injection in rats for 6 days.

Conclusions: We successfully prepared LPV/RTV ISNPs as lipid-based long-acting injection by using the ISNP nanotechnology. LPV/RTV ISNPs exhibited a sustained release behavior in both in-vivo and in-vitro studies.