Pharmaceutical Manufacturing Handbook: Production and

492 LIPOSOMES AND DRUG DELIVERY
than 50% tumor penetration of the total area evaluated , which also included extension
into surrounding normal brain. Distribution was somewhat less extensive than
with the 40 - nm liposomes, though.
The effi cacy of liposome administration with CED was demonstrated using real -
time magnetic resonance imaging (MRI) of rat brain tumors [416] . Two types of
liposomes were used: doxorubicin - loaded liposomes and gadolinium (Gd) – loaded
(MRI contrast agent) liposomes. According to the authors, MRI facilitated the distinction
of distribution between different tumor models, such as C6 gliomas and
9L - 2 gliomas. Also, after CED of Doxil, the drug presence was identifi ed in the tissue
several weeks after a single administration, while the therapeutic response achieved
was greater compared to systemic administration of Doxil. The fact that therapeutic
liposomes can be coinfused with liposomal Gd to successfully monitor the distribution
of the drug carrier in the nonhuman primate brain was shown by Saito and
co - workers [417] . A 2 : 1 ratio between the volume of distribution and the volume
of liposomes infused was found while liposomal Gd was still detectable 48 h postinfusion,
confi rming the previous fi nding of prolonged retention of liposomal Gd in
the tissues and negligible toxicity in rat. With this study, the authors showed that
CED is a technique enabling safe and extensive liposome distribution. Also, real -
time MRI is a potentially useful tool to estimate the concentration and tissue half -
lives of liposome - loaded drugs within target tissues.
However, CED might not always be successful as good technical skills are
required (if the catheter is not placed properly, the liposomes will escape within the
CSF). Also CED is an invasive technique and could cause infl ammation and neurotoxicity
and it is determined by many formulation characteristics and diffusional
properties of the latter in brain tissue [418] .
Breast Cancer Breast cancer is the second leading cause of cancer deaths in
women today (after lung cancer) and is the most common cancer among women,
excluding nonmelanoma skin cancers [419] . According to the World Health Organization,
more than 1.2 million people will be diagnosed with breast cancer this year
worldwide. Breast cancer stages range from stage 0 (very early form of cancer) to
stage IV (advanced, metastatic breast cancer). Each patient ’ s individual tumor
characteristics, state of health, genetic background, and so on, will impact her survival.
In addition, levels of stress, immune function, will to live, and other unmeasurable
factors also play a signifi cant role in a patient ’ s survival. The majority of women
with breast cancer will undergo surgery as part of their cancer treatment (lumpectomy
and mastectomy). In addition to surgery, some women will receive adjuvant
(additional) treatment (chemotherapy, radiation therapy, and drug treatments) to
stop cancer growth, spread, or recurrence. Occasionally women may be treated with
chemotherapy, radiation, or drugs without having breast surgery.
From a clinical point of view and with relevance to liposomes, administration of
either PEGylated (Doxil) or non - PEGylated liposomal doxorubicin (Myocet) has
improved the safety and tolerance of patients with breast cancer by signifi cantly
reducing the main side effect of those drugs, cardiotoxicity. However, drug effi cacy
remains the same either incorporated or not in the liposomes as this is reported
after conducting various clinical studies [420, 421] . For example, Myocet (M) received
European approval for use in patients with metastatic breast cancer at a dose of