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Bio-mimetic drug delivery systems designed to help the senior population reconstruct melatonin plasma profiles similar to those of the healthy younger population.

Li Y, Wang L, Wu L, Zhang X, Li X, Guo Z, Li H, York P, Gui S, Zhang J - Acta Pharm Sin B (2014)

Bottom Line: The secretion of melatonin (MT) is obviously different in the younger and the senior sectors of the population, and the maximum plasma concentration of seniors is only half of that in the younger population group.If exogenous MT can be supplied to senior citizens based on the secretion rate and amount of endogenous MT in the younger population by a bio-mimetic drug delivery system (DDS), an improved therapeutic effect and reduced side effects can be expected.In this research, a bio-mimetic DDS for replacement of MT was designed with in silico evaluation.

View Article: PubMed Central - PubMed

Affiliation: Anhui University of Chinese Medicine, Hefei 230038, China ; Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

ABSTRACT
The secretion of melatonin (MT) is obviously different in the younger and the senior sectors of the population, and the maximum plasma concentration of seniors is only half of that in the younger population group. If exogenous MT can be supplied to senior citizens based on the secretion rate and amount of endogenous MT in the younger population by a bio-mimetic drug delivery system (DDS), an improved therapeutic effect and reduced side effects can be expected. Based upon this hypothesis, the pharmacokinetic parameters of MT, namely, the absorption rate constant (k a), the elimination rate constant (k e), and the ratio of absorption rate (F) to the apparent volume of distribution (V) were obtained by a residual method depending on the plasma concentration curve of immediate release preparations in the healthy younger population. The dose-division method was applied to calculate the cumulative release profiles of MT achieved by oral administration of a controlled release drug delivery system (DDS) to generate plasma MT profiles similar to the physiological level-time profiles. The in vivo release of MT deduced from the healthy younger population physiological MT profiles as the pharmacokinetic output of the bio-mimetic DDS showed a two-phase profile with two different zero order release rates, namely, 4.919 μg/h during 0-4 h (r=0.9992), and 11.097 μg/h during 4-12 h (r=0.9886), respectively. Since the osmotic pump type of DDS generally exhibits a good correlation between in vivo and in vitro release behaviors, an osmotic pump controlled delivery system was designed in combination with dry coating technology targeting on the cumulative release characteristics to mimic the physiological MT profiles in the healthy younger population. The high similarity between the experimental drug release profiles and the theoretical profiles (similarity factor f 2>50) and the high correlation between the predicted plasma concentration profiles and the theoretical plasma concentration profiles (r=0.9366, 0.9163, 0.9264) indicated that a prototype bio-mimetic drug delivery system of MT was established. The similarity factors between the experimental drug release profiles and the theoretical release profile were all larger than 50 both in periods of 0-4 h and 4-12 h, namely, 68.8 and 57.3 for the first batch (Batch No. 20131031), 76.7 and 50.2 for the second batch (Batch No. 20131101), and 73.7 and 51.1 for the third batch (Batch No. 20131126), respectively. The correlation coefficients between the predicted plasma concentration profiles based on the release profiles of the bio-mimetic DDS and physiological profiles were 0.9366 (Batch No. 20131031), 0.9163 (Batch No. 20131101), 0.9264 (Batch No. 20131126), respectively. Since the pharmacokinetic profile of MT in any kind of animal differs markedly from that of human beings, it is impossible to test the bio-mimetic DDS in animals directly. Therefore, the predicted pharmacokinetic profile based upon the in vitro release kinetics is an acceptable surrogate for the conventional animal test. In this research, a bio-mimetic DDS for replacement of MT was designed with in silico evaluation.

No MeSH data available.


Plasma concentration profiles of endogenous MT in different populations16 (◆ younger women, ■ senior women, ▲ younger men, ● senior men).
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f0015: Plasma concentration profiles of endogenous MT in different populations16 (◆ younger women, ■ senior women, ▲ younger men, ● senior men).

Mentions: The pineal gland usually begins to secrete MT and other neuropeptides during the night. Ward16 pointed out that under normal circumstances, a healthy younger population began to secrete MT at about 18:00, and a peak concentration appeared at 02:00 in the morning. Relative to this younger population, the MT peak concentration in a senior population group was delayed for an hour, and the maximum plasma concentration was only half of the younger group. The change of plasma concentration in different gender and age of populations also presented some differences. Specifically, the plasma concentration of the younger group was significantly higher than that of the senior group, and the area under the curve (AUC) was approximately two fold larger than that of the senior group (Fig. 3).


Bio-mimetic drug delivery systems designed to help the senior population reconstruct melatonin plasma profiles similar to those of the healthy younger population.

Li Y, Wang L, Wu L, Zhang X, Li X, Guo Z, Li H, York P, Gui S, Zhang J - Acta Pharm Sin B (2014)

Plasma concentration profiles of endogenous MT in different populations16 (◆ younger women, ■ senior women, ▲ younger men, ● senior men).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590303&req=5

f0015: Plasma concentration profiles of endogenous MT in different populations16 (◆ younger women, ■ senior women, ▲ younger men, ● senior men).
Mentions: The pineal gland usually begins to secrete MT and other neuropeptides during the night. Ward16 pointed out that under normal circumstances, a healthy younger population began to secrete MT at about 18:00, and a peak concentration appeared at 02:00 in the morning. Relative to this younger population, the MT peak concentration in a senior population group was delayed for an hour, and the maximum plasma concentration was only half of the younger group. The change of plasma concentration in different gender and age of populations also presented some differences. Specifically, the plasma concentration of the younger group was significantly higher than that of the senior group, and the area under the curve (AUC) was approximately two fold larger than that of the senior group (Fig. 3).

Bottom Line: The secretion of melatonin (MT) is obviously different in the younger and the senior sectors of the population, and the maximum plasma concentration of seniors is only half of that in the younger population group.If exogenous MT can be supplied to senior citizens based on the secretion rate and amount of endogenous MT in the younger population by a bio-mimetic drug delivery system (DDS), an improved therapeutic effect and reduced side effects can be expected.In this research, a bio-mimetic DDS for replacement of MT was designed with in silico evaluation.

View Article: PubMed Central - PubMed

Affiliation: Anhui University of Chinese Medicine, Hefei 230038, China ; Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

ABSTRACT
The secretion of melatonin (MT) is obviously different in the younger and the senior sectors of the population, and the maximum plasma concentration of seniors is only half of that in the younger population group. If exogenous MT can be supplied to senior citizens based on the secretion rate and amount of endogenous MT in the younger population by a bio-mimetic drug delivery system (DDS), an improved therapeutic effect and reduced side effects can be expected. Based upon this hypothesis, the pharmacokinetic parameters of MT, namely, the absorption rate constant (k a), the elimination rate constant (k e), and the ratio of absorption rate (F) to the apparent volume of distribution (V) were obtained by a residual method depending on the plasma concentration curve of immediate release preparations in the healthy younger population. The dose-division method was applied to calculate the cumulative release profiles of MT achieved by oral administration of a controlled release drug delivery system (DDS) to generate plasma MT profiles similar to the physiological level-time profiles. The in vivo release of MT deduced from the healthy younger population physiological MT profiles as the pharmacokinetic output of the bio-mimetic DDS showed a two-phase profile with two different zero order release rates, namely, 4.919 μg/h during 0-4 h (r=0.9992), and 11.097 μg/h during 4-12 h (r=0.9886), respectively. Since the osmotic pump type of DDS generally exhibits a good correlation between in vivo and in vitro release behaviors, an osmotic pump controlled delivery system was designed in combination with dry coating technology targeting on the cumulative release characteristics to mimic the physiological MT profiles in the healthy younger population. The high similarity between the experimental drug release profiles and the theoretical profiles (similarity factor f 2>50) and the high correlation between the predicted plasma concentration profiles and the theoretical plasma concentration profiles (r=0.9366, 0.9163, 0.9264) indicated that a prototype bio-mimetic drug delivery system of MT was established. The similarity factors between the experimental drug release profiles and the theoretical release profile were all larger than 50 both in periods of 0-4 h and 4-12 h, namely, 68.8 and 57.3 for the first batch (Batch No. 20131031), 76.7 and 50.2 for the second batch (Batch No. 20131101), and 73.7 and 51.1 for the third batch (Batch No. 20131126), respectively. The correlation coefficients between the predicted plasma concentration profiles based on the release profiles of the bio-mimetic DDS and physiological profiles were 0.9366 (Batch No. 20131031), 0.9163 (Batch No. 20131101), 0.9264 (Batch No. 20131126), respectively. Since the pharmacokinetic profile of MT in any kind of animal differs markedly from that of human beings, it is impossible to test the bio-mimetic DDS in animals directly. Therefore, the predicted pharmacokinetic profile based upon the in vitro release kinetics is an acceptable surrogate for the conventional animal test. In this research, a bio-mimetic DDS for replacement of MT was designed with in silico evaluation.

No MeSH data available.