DEVELOPMENT OF A NOVEL TECHNOLOGY FOR TARGETED DRUGS DELIVERY INTO ADIPOSE TISSUE

Highlights

The possibility of using biodegradable microneedles from a copolymer of polylactate glycolic acid for the delivery of drugs such as sibutramine and metformin has been demonstrated. Significant differences in the rate of release were revealed depending on the type of drug: metformin release was significantly faster than sibutramine and was characterized by a maximum release rate in the first 2 hours, reaching a plateau after 24 hours and maintaining the release rate after 48 hours, in total, 7% of metformin loaded into microneedles was released into the buffer solution. During the same period of time (48 hours), only 1% of the total amount of sibutramine loaded into microneedles passed into the buffer solution. At the same time, the release rate was also highest in the first 2 hours, after which the release of the drug slowed down, but without reaching a “plateau”. Mixing of these drugs slows down their release.

Aim. Evaluation of metformin and sibutramine drugs release rate from the developed microneedles made of poly(lactic acid glycolic acid) copolymer PLGA using high-performance liquid chromatography coupled with high-resolution mass spectrometry when loading them separately into microneedles and when loading a mixture of two drugs.

Methods. The objects of the study were biosoluble microneedles made of PLGA 50:50 copolymer (10,000–40,000 g/mol, LA tolerance 48–52%, GA 48–52%, solvent – ​​acetone) filled with either metformin or sibutramine alone in different concentrations, or a mixture of both drugs. A series of model experiments were conducted: 1) the analysis of drug release from microneedles containing metformin; 2) the analysis of drug release from microneedles containing sibutramine; 3) the analysis of a mixture of drugs release from microneedles with metformin and sibutramine. Quantitative determination of metformin and sibutramine in samples was performed by high-performance liquid chromatography in combination with high-resolution mass spectrometry

Results. Metformin demonstrated the highest release rate during the initial period (the first two hours), with a gradual slowdown in the release rate and reaching a “plateau”, where the amount of substance released over 24 hours becomes comparable to the amount released over 48 hours. Sibutramine showed a significantly slower release rate than metformin under similar conditions. In samples containing a mixture of drugs, the release efficiency was significantly reduced compared to the release of the same drugs loaded into the microneedles separately

Conclusion. The developed PLGA system is suitable for providing gradual release of drugs at the required concentration in the tissue. Differences in release rates were revealed depending on the drug type and the presence or absence of admixture with another drug. Metformin demonstrated the fastest release from microneedles, while the drugs mixing resulted in a significant reduction in the release efficiency of both drugs.

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