Environmental Engineering Reference
In-Depth Information
numerous recent initiatives in the field of nanomedicine are aimed at pushing
forward with the best translatable concepts using funding and clinical proof of
concept. Such an approach is expected to generate new interests in nanomedicinal
technology with macro or micro impacts on patient benefits and therapeutic treat-
ment options.
Liposomes have greater applicability in molecular and optical imaging, vascular
targeting, and tumor cell membrane targeting, triggered drug release. As drug
delivery device, it has the advantages of reduced volume of distribution of drug
when packed within nanoliposome, advantages of reduced or nil side effects, nil
toxicity, better pharmacokinetics, and tumor extravasations, improved bioavailabil-
ity, targeting and accumulation.
Liposomal formulations have been developed to prolong drug circulating life-
time, enhance drug efficacy by increasing drug deposition, and reduce drug toxicity
by avoiding critical normal tissues. Despite the clinical or preclinical approval of
numerous liposome-based chemotherapeutics, challenges remain in the formulation
and clinical deployment of micro- and nanoparticulate liposomes, as well as
combining these novel liposomes with conventional drugs and standard-of-care
therapies. Factors requiring optimization during drug delivery system include
control of drug biodistribution, release rates of the encapsulated drug, and uptake
by target cells. Quantitative mathematical calculations of the performance of the
formulation can provide an important approach for understanding drug route,
uptake, and disposition processes, as well as their therapeutic outcomes [
98
].
Doxil, the first liposomal pharmaceutical product, received Food and Drug
Administration (FDA) approval in 1995, and now it has been widely applied as
drug carriers in clinic. For clinical use, until now, varied important types of
liposomes, like PEGylated liposomes (Doxil and Lipo-Dox), temperature-sensitive
liposomes (Thermo-Dox), CLP (EndoTAG1-1), and virosomes (Expal and Inflexal
V), have been investigated. But for clinical trials, more focus has been given on the
types of delivered drugs (BLP25lipopeptide, Cisplatin, Grb2 antisense oligodeox-
ynucleotide, Bacteriophage T4 endonuclease 5), therapeutic applications (from
topical delivery systems to portable aerosol delivery systems), and biological role
(extended blood circulation time, various drug distribution in the body, reduced
side effects). Though in clinical trials of PEGylated liposomes (Doxil and Lipo-
Dox), significant incidence of stomatitis was observed due to PEGylation. In
clinical trials, some of the new generation liposomes showed poor therapeutic
efficiency, weaker accumulation in tumors, reduced anti-tumor activity, increased
toxicity in tissues as compared to conventional free drug. Thus for clinical trials,
formulation of liposomes must be regulated based on its efficacy, clinical thera-
peutic effects, preclinical trials in animal models, and toxic side effects of liposo-
mal lipid composition [
6
].
The major challenges in the field of research in liposomal nanomedicine revolve
around strategies of increased extravasation by manipulating architecture of tumor
vasculature, improved bioavailability by increasing cell-specific internalization of
liposomal nanoparticles (LN), modulating tumor cell membrane permeability and
triggering drug release, targeted drug delivery by targeting intracellular receptors
