This review describes studies on
drug discovery using a rational formulation design and innovative, drug delivery systems (DDS) for
biomaterials such as therapeutic
peptides and
nucleotides. The
microcapsules of the
LH-RH superagonist
leuprorelin acetate prepared using the new in-water drying method and biodegradable
polymers, such as PLGA and PLA, could achieve a long-term sustained release for 1-6 months thereby facilitating easily treatment of
hormone-dependent diseases,
prostate cancer,
endometriosis, and
precocious puberty. This DDS technology showed an improvement in patient QOL and highly promoted the clinical value of the agonist. Moreover, PLGA
microcapsules of siRNAs against
VEGF, cFLIP, Raf-1, and Int6 have also been developed to treat various
cancers and
arteriosclerosis obliterans. To develop therapeutic
nucleotides, a particle design is created using functional
peptides, such as
cell penetrating peptides (
CPP), nuclear localizing signals (NLS), tight junction reversible openers (
AT1002),
bombesin, and
dynein light chain-associated sequences.
siRNA use should lead to a paradigm shift in
drug discovery against various diseases. Tat analog with NLS could enhance the potency of a vaginal
DNA vaccine. The artificial Tat
CPP of STR-CH(2)R(4)H(2)C synthesized in our laboratory could efficiently deliver siRNAs into many types of cells and enhance the
therapeutic effects for treating
sarcoma,
atopic dermatitis,
allergic rhinitis, and
asthma by intratumor injection and inhalation of the nanoparticles. Tat and
AT1002 analogs used to treat
atopic dermatitis in mice increased cell membrane permeability to siRelA, a
siRNA against a subclass of NF-κB, and exhibited striking therapeutic and preventive effects.