Gene Delivery Using Chemical Methods - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 128

used in clinical practice in gene delivery, as evident from clinical trial studies, poly-
meric vectors have gained favor owing to their safety, cost-effectiveness, ease of han-
dling, and manufacturing. In this chapter, the structure, function, and mechanism of
various polymeric vectors and their applicability are elaborated upon. However, the
underlying mechanism for transgene expression of nonviral vector-based gene trans-
fer is not completely understood.
Three basic mechanisms of DNA polymer complex formation are:

1. condensation of DNA with polymers (e.g., poly[L-lysine] (PLL) and copolymers, polyeth-
ylenimine [PEI] and copolymers),
2. encapsulation of DNA into the polymers (e.g., poly(-amino esters), polylactide,
poly(lactide- co -glycolide), and
3. complexation of DNA to the surface of preformed polymeric nanoparticles (NPs) grafted
with cationic surfactants or polysaccharides (polyalkylcyanoacrylate [PACA], poly[lactide-
co -glycolide]).

Cationic polymeric gene vectors, owing to their positive charge, usually form
complexes as a result of electrostatic interaction between cationic amino groups of
polymeric gene vectors and anionic phosphate groups of DNA [9,10] . The so-formed
complexes are called polyplexes. The group of polymers used in gene delivery is
broadly divided into two types: condensing and noncondensing polymers, as shown
in Fig. 4.1 .

4.2.1 Condensing Polymers
Condensing cationic polymeric gene vectors, owing to their condensing property and
positive charge, usually condense DNA to 1/1000-1/10,000 of its original volume,
by forming complexes. Examples of condensing polymers explored for gene delivery

Polymeric carriers for gene delivery

Condensing
polymers

Noncondensing
polymers

Nonbiodegradable
polymers

Biodegradable
polymers

Nonbiodegradable
polymers

Biodegradable
polymers

Poly ( L -lysine)
Polyethylenimine
Poly(2-(dimethyal-
amino)ethyl
methacrylate)

Poly( β -amino
esters)
Polyesters

Poloxamers
(Pluronic ® Block
copolymers)
Poly ( N -vinyl
pyrrolidone)

Poly ( D , L -lactide- co -
glycolide)
Poly
(alkyalcynoacrylate)

Figure 4.1 A schematic showing different types of polymeric vectors for gene delivery.