Advances in the oral delivery of protein and peptide therapeutics
Recent
advancements in biologics have unleashed tremendous opportunities in addressing
unmet medical needs taking healthcare to new heights. Biologics have shown
promising leads
to the treatment of debilitating conditions like diabetes,
cancer, autoimmune diseases that affect millions worldwide. The success
biologics are
often attributed to their high specificity and enhanced
therapeutic potential over conventional small molecules. It should come as no
surprise then that
almost 80% of the novel drugs approved by the US FDA in 2020
constituted of biologics. Currently, quite 800 peptide drugs
are within
the pipeline and around 197 peptide-based drugs are commercialised. the worldwide biologics
market stood at an estimated USD 269,152 million in 2019 and is predicted to
grow at a CAGR of 14.7% to succeed in up to USD 464,604 million by 2023.
Asia-Pacific especially accounted
for the most
important market with a whopping 53.1% share of worldwide biologics
in 2019. With a high number of first-generation biologics now going off-patent,
there’s immense scope for development and growth of biosimilars now.
Biologics offer distinct advantages that tiny molecule
drugs don't ,
but they're much more complex
to develop and manufacture. Biologics have high relative molecular mass ,
are temperature and lightweight sensitive, vulnerable to shearing and
degradation, and not as robust as small molecules. These limitations make it
difficult to formulate them into conventional dosage forms like capsules
or tablets and
thus most biologics are developed into injection.
However, to
supply patients with a more convenient dosage form that's easier
to administer and encourages greater patient compliance, non-invasive routes of
administration for delivering biologics are currently being explored.
Although only
a few of those delivery systems have succeeded commercially,
the growing numbers of patents and clinical trials during this direction
surely cast a
light-weight of hope for the longer term . This
blog aims to
debate the emerging trends of the non-invasive routes for
delivery of protein and peptide therapeutics and what the longer term may hold.
Oral
peptide delivery: Technologies driving market trends
To aid the oral delivery of macromolecules,
formulation scientists are exploring numerous advanced drug delivery
strategies like polymer
conjugation, chemical modifications, nanoencapsulation, polymer nanocarriers,
lipidic nanocarriers, inorganic nanoparticles, microneedles also as
hybrid carriers. Some therapeutic peptides have also successfully made it to
the market as oral dosage forms.
Peptides with lower relative molecular mass (preferably but 6000
daltons) or those possessing a cyclic structure are found to point out good
chances of being delivered orally. Cyclosporin (NeoralÒ, Novartis) is one among the
few commercially available oral peptide therapeutics available within the sort of oral
solution and liquid filled soft gelatin capsule. In aqueous condition, the
formulation is converted to a microemulsion in place . Its lipophilic
nature and cyclic structure help in intestinal absorption inhibiting
proteolytic degradation to an excellent degree. Oral octreotide, approved by
USFDA for future maintenance
treatment of acromegaly, is another oral biologic that has been developed as a
delayed release capsule (MYCAPSSAÒ, Chiasma Inc.). The formulation uses a singular technology
called Transient Permeability Enhancer or TPE.
The
world of novel
excipients is
that the next big thing within the biopharmaceutical
industry. Scientists everywhere are now trying to find multi-functional
excipients which
will help in efficient delivery of biomolecules through the
oral route. PeptelligenceÒ platform technology developed by Enteris Biopharma
has been described as a “formulation toolbox” of excipients, composed of an
innovative combination of GRAS category excipients. The excipient combination
consists of pH lowering, membrane wetting, charge dispersal and solubilising
agents which improve permeability and bioavailability of the peptide API
without affecting its physicochemical properties. Emisphere Technologies Inc.
has developed a
singular technology called EligenÒ SNAC comprising Sodium
N-[8-(2-hydroxy benzoyl) amino] caprylate which may be a functional
excipient designed to reinforce intestinal absorption and permeability of
peptides and proteins upon oral delivery.
Merrion Pharmaceuticals, a corporation dedicated
towards development of orally deliverable dosage sorts of drugs that are
generally given via parenteral routes. they need developed novel
excipients with GRAS ingredients using their proprietary GIPETÒ platform
technology. They contains patented absorption enhancers that activate
micelle formation, facilitating drug absorption. Merrion has partnered with
Novo Nordisk to develop oral formulations for insulin analogues.
Another interesting technology for oral delivery
of biologics has been developed by Rani Therapeutics and is named the
RaniPillTM which may be a robotic enteric coated capsule with a balloon
like structure that inflates upon generation of CO2 at higher pH thanks to dissolution
of capsule shell. The peptide is contained in sucrose based dissolvable
microneedles that pierce the intestinal wall and deliver the peptide.
Advanced
Systems for oral peptide delivery
Systems supported lipidic,
polymeric, and inorganic nanocarriers have shown great potential for oral
delivery of proteins and peptides. Self-nanoemulsifying systems have gained
wide acceptance for delivery of proteins and peptides and are proven to enhance the
intestinal permeability of certain peptides. Other lipid based nanocarriers
investigated for delivery of proteins and peptides are lipid nanoparticles like
solid lipid nanoparticles, nanostructured lipid carriers, lipidic micelles,
nanocapsules, microemulsions and liposomes. Inherent properties of lipidic
cores in such carriers include peptide protection, controlled drug release,
enhanced tissue and mucus permeability, stability and biocompatibility. Select
range of natural biodegradable polymers like chitosan and its
derivatives, alginates, starch and its derivatives, carbohydrates, and g-PGA
based materials are being studied for oral delivery of peptides. Synthetic
polymers that are researched
upon include PLGA, PGA, PCL, and PEA. There has also been a growing specialise in engineering
hybrid systems involving both lipid and polymer components so as to
supplement the solubilising capacity of lipids with the stabilising matrix of
polymers. within
the inorganic category, silica nanoparticles are getting highly
popular thanks
to their multifunctional, biocompatible and biodegradable
nature. Ceramics based aquasomes are another emerging category of inorganic
nanoparticles being studied for the oral delivery of proteins and peptides.
Future
perspectives
The past decade has witnessed an enormous rise within the growth
of biopharmaceutical industry and therefore the focus is now moving towards delivery
of the sensitive biomolecules
via non-invasive routes like oral route – oral route being the foremost preferential thanks to a number of the
very obvious reasons like patient compliance, simple manufacturing and
reduction in cost. because of innovative technologies that have made
possible modulations in API, excipients, delivery carriers. However,
majority of
those technologies are still within the ir nascent
stages and
that they have an extended thanks to go
before they're successfully
launched in the market. Nonetheless, the longer term of oral
biologics definitely looks bright.
Pharmaceutical Solutions
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