Quinine: Redesigned and Rerouted
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, f...
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creator | Agbo, Chinazom Precious Ugwuanyi, Timothy Chukwuebuka Eze, Osita Christopher Onugwu, Adaeze Linda Echezona, Adaeze Chidiebere Nwagwu, Chinekwu Sherridan Uzondu, Samuel Wisdom Ogbonna, John Dike Ugorji, Lydia Onyinyechi Nnamani, Petra Obioma Akpa, Paul Achile Reginald-Opara, Joy Nneji Ogbodo, John Onyebuchi McConville, Christopher Attama, Anthony Amaechi Momoh, Mumuni Audu Ofokansi, Kenneth Chibuzor |
description | 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. |
doi_str_mv | 10.3390/pr11061811 |
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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.</description><identifier>ISSN: 2227-9717</identifier><identifier>EISSN: 2227-9717</identifier><identifier>DOI: 10.3390/pr11061811</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Antimalarial agents ; Bitter taste ; Brain research ; Doxycycline ; Drugs ; Halofantrine ; Intranasal administration ; Lipids ; Malaria ; Mucosa ; Multidrug resistance ; Nanotechnology ; Oral administration ; Parasite resistance ; Parasites ; Permeation ; Poloxamers ; Quinine ; Side effects ; Solids ; Surfactants ; Temperature ; Zeta potential</subject><ispartof>Processes, 2023-06, Vol.11 (6), p.1811</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c293t-5842a5cf2f0a12171e028e4c1f729891c1b1b9ff30e891461a7cf5e76b63a14d3</cites><orcidid>0000-0001-9677-1288 ; 0000-0001-5666-0540 ; 0000-0002-5751-2280</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Agbo, Chinazom Precious</creatorcontrib><creatorcontrib>Ugwuanyi, Timothy Chukwuebuka</creatorcontrib><creatorcontrib>Eze, Osita Christopher</creatorcontrib><creatorcontrib>Onugwu, Adaeze Linda</creatorcontrib><creatorcontrib>Echezona, Adaeze Chidiebere</creatorcontrib><creatorcontrib>Nwagwu, Chinekwu Sherridan</creatorcontrib><creatorcontrib>Uzondu, Samuel Wisdom</creatorcontrib><creatorcontrib>Ogbonna, John Dike</creatorcontrib><creatorcontrib>Ugorji, Lydia Onyinyechi</creatorcontrib><creatorcontrib>Nnamani, Petra Obioma</creatorcontrib><creatorcontrib>Akpa, Paul Achile</creatorcontrib><creatorcontrib>Reginald-Opara, Joy Nneji</creatorcontrib><creatorcontrib>Ogbodo, John Onyebuchi</creatorcontrib><creatorcontrib>McConville, Christopher</creatorcontrib><creatorcontrib>Attama, Anthony Amaechi</creatorcontrib><creatorcontrib>Momoh, Mumuni Audu</creatorcontrib><creatorcontrib>Ofokansi, Kenneth Chibuzor</creatorcontrib><title>Quinine: Redesigned and Rerouted</title><title>Processes</title><description>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.</description><subject>Antimalarial agents</subject><subject>Bitter taste</subject><subject>Brain research</subject><subject>Doxycycline</subject><subject>Drugs</subject><subject>Halofantrine</subject><subject>Intranasal administration</subject><subject>Lipids</subject><subject>Malaria</subject><subject>Mucosa</subject><subject>Multidrug resistance</subject><subject>Nanotechnology</subject><subject>Oral administration</subject><subject>Parasite resistance</subject><subject>Parasites</subject><subject>Permeation</subject><subject>Poloxamers</subject><subject>Quinine</subject><subject>Side effects</subject><subject>Solids</subject><subject>Surfactants</subject><subject>Temperature</subject><subject>Zeta potential</subject><issn>2227-9717</issn><issn>2227-9717</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNpNUE1LAzEQDaJg0V78BQVvwtbMZHeTeCvFLyiIoueQZiclpc3WZPfgvzdSQWcOM2-Y92Z4jF0Bnwuh-e0hAfAWFMAJmyCirLQEefqvP2fTnLe8hAahmnbCZq9jiCHS3eyNOsphE6mb2dgVmPpxoO6SnXm7yzT9rRfs4-H-fflUrV4en5eLVeVQi6FqVI22cR49t4AggTgqqh14iVppcLCGtfZecCqobsFK5xuS7boVFupOXLDro-4h9Z8j5cFs-zHFctKgKhItV01dtubHrY3dkQnR90OyrmRH--D6SD6U-UKWdxRig4VwcyS41OecyJtDCnubvgxw8-Oa-XNNfANzyFuu</recordid><startdate>20230601</startdate><enddate>20230601</enddate><creator>Agbo, Chinazom Precious</creator><creator>Ugwuanyi, Timothy Chukwuebuka</creator><creator>Eze, Osita Christopher</creator><creator>Onugwu, Adaeze Linda</creator><creator>Echezona, Adaeze Chidiebere</creator><creator>Nwagwu, Chinekwu Sherridan</creator><creator>Uzondu, Samuel Wisdom</creator><creator>Ogbonna, John Dike</creator><creator>Ugorji, Lydia Onyinyechi</creator><creator>Nnamani, Petra Obioma</creator><creator>Akpa, Paul Achile</creator><creator>Reginald-Opara, Joy Nneji</creator><creator>Ogbodo, John Onyebuchi</creator><creator>McConville, Christopher</creator><creator>Attama, Anthony Amaechi</creator><creator>Momoh, Mumuni Audu</creator><creator>Ofokansi, Kenneth Chibuzor</creator><general>MDPI AG</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>KB.</scope><scope>LK8</scope><scope>M7P</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><orcidid>https://orcid.org/0000-0001-9677-1288</orcidid><orcidid>https://orcid.org/0000-0001-5666-0540</orcidid><orcidid>https://orcid.org/0000-0002-5751-2280</orcidid></search><sort><creationdate>20230601</creationdate><title>Quinine: Redesigned and Rerouted</title><author>Agbo, Chinazom Precious ; 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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.</abstract><cop>Basel</cop><pub>MDPI AG</pub><doi>10.3390/pr11061811</doi><orcidid>https://orcid.org/0000-0001-9677-1288</orcidid><orcidid>https://orcid.org/0000-0001-5666-0540</orcidid><orcidid>https://orcid.org/0000-0002-5751-2280</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Antimalarial agents Bitter taste Brain research Doxycycline Drugs Halofantrine Intranasal administration Lipids Malaria Mucosa Multidrug resistance Nanotechnology Oral administration Parasite resistance Parasites Permeation Poloxamers Quinine Side effects Solids Surfactants Temperature Zeta potential |
title | Quinine: Redesigned and Rerouted |
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