Page 36 - Drug Discovery and Development: Prospects and Challenges

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maltodextrin proniosomes, the drug exhibited fast absorption with
183% relative bioavailability compared to the pure drug, while glucose
proniosomes demonstrated 112% relative bioavailability (Sammour et
al., 2019).
PEGylation can be used to increases the size and molecular weight
of proteins and peptides while also improving their pharmacokinetics
and pharmacodynamics by increasing their water solubility, therefore,
protecting them from enzymatic degradation, lowering renal clearance,
and decreasing the immunogenic and antigenic responses (Milla et al.,
2011). The Doxil 5 (PEGylated liposomal doxorubicin) was the first
®
clinically approved liposomal nanomedicine by the FDA for the treatment
of advanced ovarian cancer, multiple myeloma, and HIV-associated
Kaposi sarcoma (Gkionis et al., 2020).
Cancer is characterised by the heterogeneous proliferation of cells
with the intrinsic potential to metastasise to major organs (Li et al., 2010).
Multidrug resistance refers to the process in which cancer cells develop
resistance against a variety of anti-cancer treatments that are structurally
and functionally distinct from the initial drug after being exposed to it.
The resistance is associated with drug efflux and metabolism, whether
it is intrinsic or acquired (Szakács et al., 2006).
A multiagent-mechanistic treatment method using free drug
cocktail treatment alternatives is used to treat such cancers. Previously,
the medication combination of doxorubicin hydrochloride (DOX)
and vincristine sulfate (VCR) was successful in treating aggressive
adenocarcinomas (Mokhtari et al., 2017). The two most significant
approval of the combination of drug nanocarrier includes Vyxeos™ and
chimeric antigen receptor T cells (CAR-T) therapy, Kymriah™ and or
Yescarta™ (Ghosh et al., 2019).
The b-mangostin is an active compound from G. mangostana with
low solubility due to its hydrophobic property. Based on our preliminary
study, b-mangostin in its original form (non-formulated) showed strong
activity against Caco-2 cells (IC50= 8.27 μg/mL). It is expected that the
activity against multidrug-resistant cancer cells would be enhanced by
improving its formulation. The study was also designed to incorporate
b-mangostin to a PEGylated liposome loaded (Figure 22) with
doxorubicin to overcome multidrug-resistant of colon cancer cells to
provide a synergistic effect (Taher, 2021, unpublished).