Environmental Engineering Reference
In-Depth Information
agents including drugs, plasmid DNA (pDNA), antisense oligonucleotides (ASOs),
and small interfering RNA (siRNA) with liposomes of 100 nm diameter generating
high drug to liposomes nanoparticles ratio thus allowing gene delivery, gene
correction, drug delivery with more circulation time, greater retention, and accu-
mulation of therapeutic agents in disease niche. Different drug molecules, including
antimicrobial and anticancer agents, peptide hormones, chelating agents, vaccines,
enzymes, proteins, and genetic materials, have been incorporated into the aqueous
or lipid phases of liposomes, with varied sizes, compositions, and other character-
istics, to provide selective delivery to the target site for in vivo therapeutics.
Biocompatible, biodegradable, nonimmunogenic, liposomes or drug encapsulated
nanoparticle liposomes, coated with bioactive moieties has revolutionized the drug
delivery system thereby reducing drug side effects and increasing efficiency and
therapeutic property. Researches on diverse modifications of liposomes for targeted
drug delivery are in process. In this chapter, we summarized the recent develop-
ments in the design and modification of liposomes and their potential application in
delivery of drugs and diverse types of therapeutic agents applied in targeting a vast
array of diseases.
9.1.1 Liposome Nanomedicine: Formulation
Liposomes are the oldest nanotherapeutic bioagent that have been used clinically.
The designing of liposomal products incorporates consideration of the critical
parameters that determine the in vivo liposomal performance for parenteral admin-
istration including particle size, surface charge, membrane composition, and fluid-
ity. The first liposomal formulation of the cytotoxic anticancer drug doxorubicin
(DOX) were launched in the early 1990s [
6
,
7
]. Liposome encapsulation of DOX
increases its half-life and distribution in tumor tissues, with reduced acute and
cumulative cardiotoxicity. Doxil, the PEGylated liposomal formulation of DOX is
being applied in the treatment of refractory Kaposi's sarcoma, ovarian and recurrent
breast cancers (BCs) [
5
-
7
]. Liposome encapsulated therapeutic AmBisome from
Gilead Sciences Ltd has been clinically approved over amphotericin B to overcome
the associated side effects like infusion-related reactions and nephrotoxicity on
chronic usage of amphotericin B. The increased uptake of amphotericin B-loaded
liposomes by the reticulo endothelial (RE) system is noted for the small size and
negative charge of the liposomes [
5
].
Several techniques, including the dense gas and supercritical fluid techniques,
ether/ethanol injection, Bangham method, detergent depletion, reverse-phase evap-
oration, and emulsion methods, have been reported for preparing liposomes
(Fig.
9.1a, b
) with high-entrapment efficiency with increased therapeutic index,
narrow particle size distribution, long-term stability via encapsulation, site avoid-
ance effect with reduced elimination, selective passive targeting to tumor tissues
(liposomal DOX), and target-specific active drug loading property. Due to the
differences in preparation methods and lipid composition,
liposomes were
