Limits...
Development of a liposomal nanodelivery system for nevirapine.

Ramana LN, Sethuraman S, Ranga U, Krishnan UM - J. Biomed. Sci. (2010)

Bottom Line: The use of different antiretroviral drugs (ARV) is significantly limited by severe side-effects that further compromise the quality of life of the AIDS patient.Thermal analysis of the drug encapsulated liposomes indicated the formation of a homogenous drug-lipid system.We propose that nevirapine-loaded liposomal formulations reported here could improve targeted delivery of the anti-retroviral drugs to select compartments and cells and alleviate systemic toxic side effects as a consequence.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Nanotechnology & Advanced Biomaterials, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613 401, India.

ABSTRACT

Background: The treatment of AIDS remains a serious challenge owing to high genetic variation of Human Immunodeficiency Virus type 1 (HIV-1). The use of different antiretroviral drugs (ARV) is significantly limited by severe side-effects that further compromise the quality of life of the AIDS patient. In the present study, we have evaluated a liposome system for the delivery of nevirapine, a hydrophobic non-nucleoside reverse transcriptase inhibitor. Liposomes were prepared from egg phospholipids using thin film hydration. The parameters of the process were optimized to obtain spherical liposomes below 200 nm with a narrow polydispersity. The encapsulation efficiency of the liposomes was optimized at different ratios of egg phospholipid to cholesterol as well as drug to total lipid. The data demonstrate that encapsulation efficiency of 78.14% and 76.25% were obtained at egg phospholipid to cholesterol ratio of 9:1 and drug to lipid ratio of 1:5, respectively. We further observed that the size of the liposomes and the encapsulation efficiency of the drug increased concomitantly with the increasing ratio of drug and lipid and that maximum stability was observed at the physiological pH. Thermal analysis of the drug encapsulated liposomes indicated the formation of a homogenous drug-lipid system. The magnitude of drug release from the liposomes was examined under different experimental conditions including in phosphate buffered saline (PBS), Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal bovine serum or in the presence of an external stimulus such as low frequency ultrasound. Within the first 20 minutes 40, 60 and 100% of the drug was released when placed in PBS, DMEM or when ultrasound was applied, respectively. We propose that nevirapine-loaded liposomal formulations reported here could improve targeted delivery of the anti-retroviral drugs to select compartments and cells and alleviate systemic toxic side effects as a consequence.

Show MeSH

Related in: MedlinePlus

Correlation between the mean particle size (white circle) and percent encapsulation efficiency (Black square) at various drug-lipid ratios.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2914021&req=5

Figure 4: Correlation between the mean particle size (white circle) and percent encapsulation efficiency (Black square) at various drug-lipid ratios.

Mentions: Since lipid composition could have significant impact on liposome size, stability, drug loading and delivery functions, we examined the physical properties of the liposomes synthesized at varying ratios of egg phospholipids and cholesterol. The encapsulation efficiency of liposomes constituted from varying concentrations of phospholipid and cholesterol for nevirapine loading was compared (Figure 3). The encapsulation efficiency of the liposomes was significantly influenced by the presence of cholesterol and its drug to lipid ratio. Liposomes consisting of cholesterol (at 9:1 ratio) showed significantly increased encapsulation efficiency for nevirapine as compared to the particles without cholesterol (at 10:0 ratio, p < 0.05). The enhanced loading capacity of the liposomes may be attributed to a combined effect of increased hydrophobicity and or increased liposome size due to cholesterol incorporation [45]. Importantly, further increase in the cholesterol content did not enhance drug loading capacity of the liposomes instead, in fact reduced the encapsulation efficiency. High levels of cholesterol have been reported to interfere with the close packing of lipids in the vesicles by contributing to an increase in membrane fluidity which results in an increased distribution of aqueous phase within the liposomal vesicle thereby reducing the encapsulation of the hydrophobic nevirapine [46]. The encapsulation efficiency of the liposomes was not significantly affected by the substitution of egg phospholipids with synthetic egg phosphatidyl choline probably because phosphatidyl choline is the major constituent in egg phospholipid mixture. We measured the effect of the drug-lipid ratio on liposome diameter and encapsulation efficiency. The results demonstrate that the size of the drug loaded liposomes decreased significantly from 188 ± 1.2 nm to 73 ± 7.8 nm when the drug-lipid ratio was decreased from 1:10 to 1:1 (Figure 4). A reduction in the liposome size is expected to shrink the aqueous volume of the liposome resulting in lesser encapsulation of a lipophilic drug like nevirapine [47]. Furthermore, significant increase in the amount of drug loading was observed with increasing drug-lipid ratio up to 1:5 (p < 0.05)but not beyond these ratio (Figure 4).


Development of a liposomal nanodelivery system for nevirapine.

Ramana LN, Sethuraman S, Ranga U, Krishnan UM - J. Biomed. Sci. (2010)

Correlation between the mean particle size (white circle) and percent encapsulation efficiency (Black square) at various drug-lipid ratios.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2914021&req=5

Figure 4: Correlation between the mean particle size (white circle) and percent encapsulation efficiency (Black square) at various drug-lipid ratios.
Mentions: Since lipid composition could have significant impact on liposome size, stability, drug loading and delivery functions, we examined the physical properties of the liposomes synthesized at varying ratios of egg phospholipids and cholesterol. The encapsulation efficiency of liposomes constituted from varying concentrations of phospholipid and cholesterol for nevirapine loading was compared (Figure 3). The encapsulation efficiency of the liposomes was significantly influenced by the presence of cholesterol and its drug to lipid ratio. Liposomes consisting of cholesterol (at 9:1 ratio) showed significantly increased encapsulation efficiency for nevirapine as compared to the particles without cholesterol (at 10:0 ratio, p < 0.05). The enhanced loading capacity of the liposomes may be attributed to a combined effect of increased hydrophobicity and or increased liposome size due to cholesterol incorporation [45]. Importantly, further increase in the cholesterol content did not enhance drug loading capacity of the liposomes instead, in fact reduced the encapsulation efficiency. High levels of cholesterol have been reported to interfere with the close packing of lipids in the vesicles by contributing to an increase in membrane fluidity which results in an increased distribution of aqueous phase within the liposomal vesicle thereby reducing the encapsulation of the hydrophobic nevirapine [46]. The encapsulation efficiency of the liposomes was not significantly affected by the substitution of egg phospholipids with synthetic egg phosphatidyl choline probably because phosphatidyl choline is the major constituent in egg phospholipid mixture. We measured the effect of the drug-lipid ratio on liposome diameter and encapsulation efficiency. The results demonstrate that the size of the drug loaded liposomes decreased significantly from 188 ± 1.2 nm to 73 ± 7.8 nm when the drug-lipid ratio was decreased from 1:10 to 1:1 (Figure 4). A reduction in the liposome size is expected to shrink the aqueous volume of the liposome resulting in lesser encapsulation of a lipophilic drug like nevirapine [47]. Furthermore, significant increase in the amount of drug loading was observed with increasing drug-lipid ratio up to 1:5 (p < 0.05)but not beyond these ratio (Figure 4).

Bottom Line: The use of different antiretroviral drugs (ARV) is significantly limited by severe side-effects that further compromise the quality of life of the AIDS patient.Thermal analysis of the drug encapsulated liposomes indicated the formation of a homogenous drug-lipid system.We propose that nevirapine-loaded liposomal formulations reported here could improve targeted delivery of the anti-retroviral drugs to select compartments and cells and alleviate systemic toxic side effects as a consequence.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Nanotechnology & Advanced Biomaterials, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613 401, India.

ABSTRACT

Background: The treatment of AIDS remains a serious challenge owing to high genetic variation of Human Immunodeficiency Virus type 1 (HIV-1). The use of different antiretroviral drugs (ARV) is significantly limited by severe side-effects that further compromise the quality of life of the AIDS patient. In the present study, we have evaluated a liposome system for the delivery of nevirapine, a hydrophobic non-nucleoside reverse transcriptase inhibitor. Liposomes were prepared from egg phospholipids using thin film hydration. The parameters of the process were optimized to obtain spherical liposomes below 200 nm with a narrow polydispersity. The encapsulation efficiency of the liposomes was optimized at different ratios of egg phospholipid to cholesterol as well as drug to total lipid. The data demonstrate that encapsulation efficiency of 78.14% and 76.25% were obtained at egg phospholipid to cholesterol ratio of 9:1 and drug to lipid ratio of 1:5, respectively. We further observed that the size of the liposomes and the encapsulation efficiency of the drug increased concomitantly with the increasing ratio of drug and lipid and that maximum stability was observed at the physiological pH. Thermal analysis of the drug encapsulated liposomes indicated the formation of a homogenous drug-lipid system. The magnitude of drug release from the liposomes was examined under different experimental conditions including in phosphate buffered saline (PBS), Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal bovine serum or in the presence of an external stimulus such as low frequency ultrasound. Within the first 20 minutes 40, 60 and 100% of the drug was released when placed in PBS, DMEM or when ultrasound was applied, respectively. We propose that nevirapine-loaded liposomal formulations reported here could improve targeted delivery of the anti-retroviral drugs to select compartments and cells and alleviate systemic toxic side effects as a consequence.

Show MeSH
Related in: MedlinePlus