Poly(beta-amino ester)s as gene delivery vehicles: challenges and opportunities

Abstract

Introduction: Gene delivery technologies are being developed for an increasing number of biomedical applications, with delivery vehicles including viruses and non-viral materials. Among biomaterials used for non-viral gene delivery, poly(beta-amino ester)s (PBAEs), a class of synthetic, biodegradable polymers, have risen as a leading gene delivery vehicle that has been used for multiple applications in vitro and in vivo.Areas covered: This review summarizes the key properties of PBAEs and their development, including a discussion of the advantages and disadvantages of PBAEs for gene delivery applications. The use of PBAEs to improve the properties of other drug delivery vehicles is also summarized. Expert opinion:PBAEs are designed to have multiple characteristics that are ideal for gene delivery, including their reversible positive charge, which promotes binding to nucleic acids as well as imparting high buffering capacity, and their rapid degradability under mild conditions. Simultaneously, some of their properties also lead to nanoparticle instability and low transfection efficiency in physiological environments. The ease with which PBAEs can be chemically modified

Application of Non-Viral Vectors in Drug Delivery and Gene Therapy

“…There are four main types of production methods: solvent evaporation, emulsification–solvent diffusion, solvent displacement and monomer polymerization [ 59 ]. Various polymers such as dendrimers, polylactic acid (PLA), polyethylenimine (PEI), and chitosan (CS) have been widely used in delivery systems [ 51 , 64 , 65 , 66 , 67 , 68 ]. Table 3 summarizes the structural characteristics, synthesis methods and properties of several polymer materials.…”

“…The positive charge of poly(beta-amino ester)s can bind to nucleic acids and be internalized into cells. At the same time, they can escape from the endolysosomal compartment and release nucleic acids into the appropriate cell compartment for gene delivery through a variety of targeted degradation mechanisms [ 68 ]. In addition, abundant functional groups provide multiple modification sites for amino acid derived biopolymers.…”

Nano‐Oncologicals: A Tortoise Trail Reaching New Avenues

“…[251] An efficacy study with a siRNA against BRD4, a key gene associated with the androgen-receptor mediated signaling and involved in aggressive metastatic phenotype, showed potent inhibition of tumor growth. [251] Other polymers such as polyethyleneimine (PEI), [252] chitosan, [253] protamine, [254,255] poly-l-lysine (PLL), polyarginine, and, more recently, poly(β-amino esters) (PBAE) [256] and their derivatives, have been extensively studied for nucleic acid delivery. Both PEI and chitosan exhibit high buffering capacity For an efficient cancer treatment, the first step when developing RNA-based therapies consists of the genetic profiling and establishment of the tumor characteristics, so the target genes and appropriate combination therapies can be identified.…”

Photocrosslinked Bioreducible Polymeric Nanoparticles for Enhanced Systemic siRNA Delivery as Cancer Therapy

“…Poly( β -amino ester)s (PBAE)s are one class of biodegradable cationic polymers being explored for nucleic acid delivery including for plasmid DNA, and with polymer structural modifications for siRNA. [ 10 – 13 ] This is due to multiple characteristics including their reversible charge, which promotes binding of RNA therapeutics as well as high buffering capacity for endosomal escape, and their degradability by hydrolysis into nontoxic byproducts under aqueous conditions. [ 14 , 15 ] Despite the promising characteristics of PBAEs and cationic nanoparticles in general, positive surface charge when injected often leads to low transfection efficacy following systemic administration due to nonspecific interactions with serum proteins and nanoparticle aggregation, resulting in poor colloidal stability and clearance by the mononuclear phagocyte system.…”