Background Poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) are among the well-documented FDAapproved polymers used for the preparation of safe and effective vaccine, drug and gene delivery systems using well-described reproducible methods of fabrication. Various nano and microparticulates are fabricated using these polymers. Their successful performance relies on PLA and PLGA biocompatibility and degradability characteristics. Area covered This review provides an overview of the biocompatibility and biodegradation of PLA, PLGA and their copolymers, with a special emphasis on tissue responses for these polymers as well as their degradation pathways and drug release models. Moreover, the potential of PLA and PLGA based nano and microparticulates in various advanced biomedical applications is highlighted. Expert opinion PLA and PLGA based delivery systems show promises of releasing different drugs, proteins and nucleic acids in a stable and controlled manner and greatly ameliorating their therapeutic efficacy. In addition, advancement in surface modification and targeting of nanoparticles has extended the scope of their utility.
It is striking that all marketed SARS-CoV-2 vaccines are developed for intramuscular administration designed to produce humoral and cell mediated immune responses, preventing viremia and the COVID-19 syndrome. They have a high degree of efficacy in humans (70-95%) depending on the type of vaccine. However, little protection is provided against viral replication and shedding in the upper airways due to the lack of a local sIgA immune response, indicating a risk of transmission of virus from vaccinated individuals.
A range of novel nasal COVID-19 vaccines are in development and preclinical results in non-human primates have shown a promising prevention of replication and shedding of virus due to the induction of mucosal immune response (sIgA) in upper and lower respiratory tracts as well as robust systemic and humoral immune responses. Whether these results will translate to humans remains to be clarified. An IM prime followed by an IN booster vaccination would likely result in a better well-rounded immune response, including prevention (or strong reduction) in viral replication in the upper and lower respiratory tracts.
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