<p>Low drug permeability is a main challenge faced by ophthalmic pharmaceuticals. Novel drug delivery systems, including nanocarriers, shed new light on enhancing ocular drug bioavailability. Nanoliposomes are among promising carriers that can be tailor-made for this purpose. In this study, a new amphiphile molecule was synthesized by coupling a known penetration enhancer molecule, 2-aminomethyl-18-crown-6, and oleic acid, and incorporated into liposome. The effect of liposome constituents and the number of freeze–thaw (FT) cycles on entrapment effiency (EE%) and the percentage of the released drug (clindamycin) after 30 days of storage at − 20℃, 4℃, and room temperature (RT) was evaluated using the I-optimal experimental design. Based on the results, the concentration of cholesterol, clindamycin, and amphiphile had a positive effect and the number of FT cycle had a negative effect on EE%. The selected formulation with phosphatidylcholine:cholesterol:amphiphile molecule:clindamycin weight ratio of 100:30:20:50 has EE%, size, and zeta potential of 81.4 ± 7.2%, 123.5 ± 19 nm, and − 20.9 ± 4.7 mV, respectively. Under − 20 <InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="12668_2025_1867_Article_IEq1.gif" Format="GIF" Height="14" Rendition="HTML" Resolution="72" Type="Linedraw" Width="20" /> </InlineMediaObject> <EquationSource Format="TEX">$^\circ{\rm C}$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mmultiscripts> <mrow /> <mrow /> <mo>∘</mo> </mmultiscripts> <mi mathvariant="normal">C</mi> </mrow> </math></EquationSource> </InlineEquation> storage temperature, more drugs remained in the liposome and percent drug release at all three temperatures depended on the concentration of clindamycin and amphiphile. The drug release was in line with the first-order diffusion mechanism, as analyzed by DDSolver software. The potential of liposomes to be manipulated and transformed into multifunctional agents was proven in this study, leading us to develop a carrier that incorporates the capabilities of liposome, amphiphiles, and crown ether, which could be promising for ocular drug delivery.</p> Graphical Abstract <p></p>

Development and Optimization of a Novel Crown Ether-Incorporated Liposome for Improved Ocular Drug Delivery

期刊论文
发表日期：

2025年3月7日

查看全文

Nooshin Tasharrofi,
Mohammad Nourozi,
Zeynab Ahmadifard

摘要

Low drug permeability is a main challenge faced by ophthalmic pharmaceuticals. Novel drug delivery systems, including nanocarriers, shed new light on enhancing ocular drug bioavailability. Nanoliposomes are among promising carriers that can be tailor-made for this purpose. In this study, a new amphiphile molecule was synthesized by coupling a known penetration enhancer molecule, 2-aminomethyl-18-crown-6, and oleic acid, and incorporated into liposome. The effect of liposome constituents and the number of freeze–thaw (FT) cycles on entrapment effiency (EE%) and the percentage of the released drug (clindamycin) after 30 days of storage at − 20℃, 4℃, and room temperature (RT) was evaluated using the I-optimal experimental design. Based on the results, the concentration of cholesterol, clindamycin, and amphiphile had a positive effect and the number of FT cycle had a negative effect on EE%. The selected formulation with phosphatidylcholine:cholesterol:amphiphile molecule:clindamycin weight ratio of 100:30:20:50 has EE%, size, and zeta potential of 81.4 ± 7.2%, 123.5 ± 19 nm, and − 20.9 ± 4.7 mV, respectively. Under − 20 $^\circ{\rm C}$ $^{\circ} C$ storage temperature, more drugs remained in the liposome and percent drug release at all three temperatures depended on the concentration of clindamycin and amphiphile. The drug release was in line with the first-order diffusion mechanism, as analyzed by DDSolver software. The potential of liposomes to be manipulated and transformed into multifunctional agents was proven in this study, leading us to develop a carrier that incorporates the capabilities of liposome, amphiphiles, and crown ether, which could be promising for ocular drug delivery.

Graphical Abstract