Gene capsules as functional pharmaceutical formulations for delivery of DNA as an active substance

Abstract

Background. Capsules are solid drug forms that are well accepted by patients. Capsules usually consist of a medicinal substance with therapeutic benefits plus excipients. From a pharmaceutical point of view, DNA coding sequences can be treated as active substances.Objectives. To develop and assess gelatin capsules containing DNA based on the methods included in the Polish Pharmacopoeia XI, as well as non-pharmacopeial methods. Materials and methods.The mass uniformity of the obtained capsules was estimated. The stability of the DNA was verified using polymerase chain reaction (PCR) method. A study of the disintegration time of the gene capsules containing DNA mixed with lactose, and placebo capsules with lactose only was also performed. A dissolution test under conditions similar to the nature and specificity of the active substance (DNA) was performed. The transduction activity of the obtained capsules was assessed in cell culture conditions.Results. The DNA and lactose-based gene capsules were obtained. The capsules were characterized by mass uniformity and stability over time. Efficient transduction of B16-F10 cancer cells with the gene product from the capsule was observed using fluorescence microscopy. Groups of green fluorescent protein-positive cells were observed in the microscope field of view. Conclusions.The findings showed that it is possible to obtain a solid pharmaceutical form of the drug, i.e., a capsule containing DNA as an active substance. The gene capsules enabled the introduction of DNA into cells. This method may have valuable implications for increasing the availability of gene-based drugs for patients.