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pH Temperature Osmotic presure Redox potential

Biodegradable Stimuli sensitive
Rotary evaporation Biocompatible Smart linker
Crystalization
Bioreducible Hydrolyzable
Free drying
Filteration TLC
Click chemistry Linker
Dialysis HPLC
Nucleophilic
substitution Bioconjugate FT-IR
EDC
EDC/NHS Zero-length Synthesis Purification Characterization LC-MS
crosslinkers
DCC/NHS 1 H-NMR
DCC Avidin-biotin
13 C-NMR
system
or
HPLC-SEC
MALDI-TOF

Imaging agent Drug
Targeting agent Antibody Peptide/protein PEG

Figure 1. Schematic diagram of bioconjugates’ structure, design, synthesis, purification and characterization

Initiatives to overcome such setbacks either involved the design and development of novel new
chemotherapeutic agents, chemical or physical modifications of currently used chemotherapeutic agents or
novel smart bioconjugates . Currently, pharmaceutical industry along with academic research is investing
[5]
heavily in bioconjugate structures. The major purpose of bioconjugation is to create a stable conjugate between
two molecules via a covalent link, at least one of which is a biomolecule . By design, the covalent linkage
[6]
should be easily biologically-cleavable to enable the release of the bioactive molecule at the desired target
site. The main advantages of bioconjugation and the generated biomolecules include enhanced physical and
chemical stability in the active pharmaceutical ingredient (API) journey to the target site, providing better
safety and efficacy profiles, delivering enhanced API protection against proteolysis and immune responses
and enhancement of the targeting powers of such novel bioconjugates nanoparticulate systems .
[6]

Bioconjugate technologies offer an appealing and advantageous alternative to nanoparticulate delivery
systems with all its flexible benefits when it comes to customized design and tailored grafting along with
avoiding most of its shortcomings. Bioconjugates offer the flexibility in customized designing of personalized
products. Bioconjugates facilitate simple and easy drug (active pharmaceutical ingredient) conjugation, using
various smart biocompatible, bioreducible, or biodegradable linkers, to targeting agents, PEG layer or another
drug [Figure 1]. Such technology enables the formation of smart multi-functional platform(s) offered by
nanoparticulate carriers and bioconjugates structures. Furthermore, conjugates are still considered chemical
compounds. This fact simply allows the use of traditional analytical and manufacturing technologies in
the characterization and manufacturing of traditional active pharmaceutical ingredients offering high
probability for their successful transition from bench to bedside. Moreover, the final formulation could be a
simple injectable or solid formulation, which offers long shelf-life and enhanced stability profile.

Subsequently, bioconjugation technologies can aid in creating safer, cheaper, stable, and effective novel
therapeutics. It can also be a rate-limiting step in reinventing old drugs and imparting new functions to
them that would enhance their targetability, pharmacokinetic and pharmacodynamic parameters, and
their overall formulation patient compliance, easing their transition to market . A major focus should
[7]
be the transformation of such novel bioconjugates’ technologies from bench to bedside. The use of click
chemistry, bioconjugation technologies, ligand post-insertion and labeling techniques need to be extensively