Microencapsulation of DNA using poly( dl-lactide-co-glycolide): stability issues and release characteristics

• Published in: Journal of controlled release Vol. 61; no. 3; pp. 361 - 374
• Main Authors: Walter, Elke, Moelling, Karin, Pavlovic, Jovan, Merkle, Hans P
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 20.09.1999; Elsevier
• Subjects: Animals; Biocompatible Materials - administration & dosage; Biocompatible Materials - chemistry; Biological and medical sciences; Cattle; Cells, Cultured; Chemistry, Pharmaceutical; Delayed-Action Preparations; DNA; DNA - administration & dosage; DNA - analysis; DNA - chemistry; Drug Compounding; Drug Stability; General pharmacology; Humans; Lactic Acid - administration & dosage; Lactic Acid - chemistry; Male; Medical sciences; Microparticles; Nucleic Acid Conformation; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasmids - genetics; Poly(lactide-co-glycolide) (PLGA); Polyglycolic Acid - administration & dosage; Polyglycolic Acid - chemistry; Polymers - administration & dosage; Polymers - chemistry; Salmon; Stability; Sustained release; Testis - chemistry; Thymus Gland - chemistry; Transfection; Transfectivity; Vaccines, DNA - administration & dosage; Vaccines, DNA - chemistry; Sustained release; Stability; DNA; Microparticles; Transfectivity; Poly(lactide-co-glycolide) (PLGA); Encapsulation; Glycolic acid copolymer; Pharmaceutical technology; Transfection; Control release polymer; Vaccination; Dosage form; Drug carrier; Copolymer; Release
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(99)00151-0

The design of DNA vaccination delivery systems for the targeting of professional antigen presenting cells could be an interesting approach to elicit cytotoxic T-cell responses to fight viral infections and in cancer therapy. Stability studies with linear high and low molecular DNA and supercoiled plasmid DNA were performed in order to check their ability to withstand stress conditions applied during formulation processes. DNA was tested for integrity by the PicoGreen assay and transfectivity was assessed in cell culture transfection experiments. Double-stranded DNA is extremely stable under physiological conditions in vitro but is rapidly degraded under acidic conditions and high shear forces. Thereby, different stress factors resulted in distinct degradation patterns such as fragmentation and strand separation possibly followed by further decomposition of single-stranded DNA. DNA containing PLGA microparticles as a potential delivery system was prepared by spray-drying. Encapsulation efficiency, DNA stability and burst release varied significantly depending on the different parameters explored in this study. The microencapsulation process was altered to achieve maximal stability of encapsulated DNA by reducing exposure to shear forces and by the addition of NaHCO 3 which acts as a buffering agent and furthermore stabilizes dsDNA against mechanical degradation. Stability of DNA is maintained during the burst release phase, but massive degradation occurred during the second release phase possibly due to acidic catalyzed decomposition. In summary, we feel that microencapsulation of DNA vaccines by spray-drying offers manifold possibilities to design suitable delivery systems in terms of optimizing phagocytosis by APCs and maintaining stability of DNA in phagosomes.