Quinine: Redesigned and Rerouted

Chinazom Precious Agbo; Timothy Chukwuebuka Ugwuanyi; Osita Christopher Eze; Adaeze Linda Onugwu; Adaeze Chidiebere Echezona; Chinekwu Sherridan Nwagwu; Samuel Wisdom Uzondu; John Dike Ogbonna; Lydia Onyinyechi Ugorji; Petra Obioma Nnamani; Paul Achile Akpa; Joy Nneji Reginald-Opara; John Onyebuchi Ogbodo; Christopher McConville; Anthony Amaechi Attama; Mumuni Audu Momoh; Kenneth Chibuzor Ofokansi

LAPSE

Living Archive for Process Systems Engineering

LAPSE:2023.36358

Published Article

LAPSE:2023.36358

Quinine: Redesigned and Rerouted

Chinazom Precious Agbo, Timothy Chukwuebuka Ugwuanyi, Osita Christopher Eze, Adaeze Linda Onugwu, Adaeze Chidiebere Echezona, Chinekwu Sherridan Nwagwu, Samuel Wisdom Uzondu, John Dike Ogbonna, Lydia Onyinyechi Ugorji, Petra Obioma Nnamani, Paul Achile Akpa, Joy Nneji Reginald-Opara, John Onyebuchi Ogbodo, Christopher McConville, Anthony Amaechi Attama, Mumuni Audu Momoh, Kenneth Chibuzor Ofokansi

July 13, 2023

Quinine hydrochloride (QHCl) has remained a very relevant antimalarial drug 400 years after its effectiveness was discovered. Unlike other antimalarials, the development of resistance to quinine has been slow. Hence, this drug is to date still used for the treatment of severe and cerebral malaria, for malaria treatment in all trimesters of pregnancy, and in combination with doxycycline against multidrug-resistant malaria parasites. The decline in its administration over the years is mainly associated with poor tolerability due to its gastrointestinal (GIT) side effects such as cinchonism, complex dosing regimen and bitter taste, all of which result in poor compliance. Hence, our research was aimed at redesigning quinine using nanotechnology and investigating an alternative route for its administration for the treatment of malaria. QHCl nanosuspension (QHCl-NS) for intranasal administration was prepared using lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising Phospholipon® 90H and lipids (Softisan® 154 or Compritol®) in a 1:2 ratio, while Poloxamer® 188 (P188) and Tween® 80 (T80) were used as a stabilizer and a surfactant, respectively. The QHCl-NS formulated were in the nanosize range (68.60 ± 0.86 to 300.80 ± 10.11 nm), and highly stable during storage, though zeta potential was low (≤6.95 ± 0.416). QHCl-NS achieved above 80% in vitro drug release in 6 h. Ex vivo permeation studies revealed that formulating QHCl as NS resulted in a 5-fold and 56-fold increase in the flux and permeation coefficient, respectively, thereby enhancing permeation through pig nasal mucosa better than plain drug solutions. This implies that the rate of absorption as well as ease of drug permeation through porcine nasal mucosa was impressively enhanced by formulating QHCl as NS. Most importantly, reduction in parasitaemia in mice infected with Plasmodium berghei ANKA by QHCl-NS administered through the intranasal route (51.16%) was comparable to oral administration (52.12%). Therefore, redesigning QHCl as NS for intranasal administration has great potential to serve as a more tolerable option for the treatment of malaria in endemic areas.

Record ID

LAPSE:2023.36358

Keywords

cerebral malaria, intranasal route, nanostructured lipid carriers, parasitemia reduction, quinine hydrochloride, severe malaria, solidified reverse micellar solutions

Subject

Biosystems

Suggested Citation

Agbo CP, Ugwuanyi TC, Eze OC, Onugwu AL, Echezona AC, Nwagwu CS, Uzondu SW, Ogbonna JD, Ugorji LO, Nnamani PO, Akpa PA, Reginald-Opara JN, Ogbodo JO, McConville C, Attama AA, Momoh MA, Ofokansi KC. Quinine: Redesigned and Rerouted. (2023). LAPSE:2023.36358

Author Affiliations

Agbo CP: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria; School of Pharmacy, College of Medical and Dental Sciences, University of Birmingham, Birmingham B4 6BN, UK [ORCID]
Ugwuanyi TC: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
Eze OC: Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
Onugwu AL: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
Echezona AC: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
Nwagwu CS: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
Uzondu SW: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
Ogbonna JD: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
Ugorji LO: Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
Nnamani PO: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria [ORCID]
Akpa PA: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
Reginald-Opara JN: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
Ogbodo JO: Department of Science Laboratory Technology, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
McConville C: School of Pharmacy, College of Medical and Dental Sciences, University of Birmingham, Birmingham B4 6BN, UK
Attama AA: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Enugu State Univer [ORCID]
Momoh MA: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
Ofokansi KC: Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Enugu State, Nigeria

Journal Name

Processes

Volume

11

Issue

6

First Page

1811

Year

2023

Publication Date

2023-06-14