drug delivery systems have undergone significant development in the last two
drug delivery has defined as a formulation or a device that enables the
introduction of a therapeutic substance into the body. Biodegradable and resorbable polymers make
this possible choice for lot of new drug delivery systems.
Challenges of drug
of a therapeutic requires optimization of dosing regimens to maximize
therapeutic benefits while minimizing unwanted side effects to patients. This
optimization is governed by four (4) basic pharmacokinetic principles: 1) absorption,
2) distribution, 3) metabolism, and 4) excretion. For any given active pharmaceutical
ingredient (API), a number of considerations must be taken into account when designing
dosage regimens which include: 1) routes of administrations, 2) site of
therapeutic action, 3) the necessity of maintenance doses to ensure long-term
therapeutic benefit, and 4) size of the therapeutic window.
Controlled release drug
release drug delivery systems have the potential to augment both the bioavailability
and distribution profile of a given API. These systems have the ability to deliver
APIs at a constant rate over long periods of time, resulting in decreased
fluctuations in drug concentrations outside of a given APIs’ therapeutic window.
In turn, this can decrease the dosing frequency for a given API and ultimately lead
to increased patient compliance. The controlled release of APIs formulated for
oral dosing is well-established through the use of complexation resins and
coated reservoir systems. In contrast, non-oral controlled release drug
delivery systems have historically been more challenging.
drug delivery (e.g., intramuscular, intravenous, and subcutaneous administrations)
is required for a number of APIs due to factors that include low
bioavailability and a low tolerance for the chemical environments of the stomach
and/or GI tract. Recent advances in excipient drug delivery techniques for
parental administration have improved the ability to control a given API’s
systemic delivery rate.
electrospun materials are an ideal excipient system given their ability to
release APIs in a controlled manner over days rather than minutes/hours. These
materials are also optimal due to their ability to act as a scaffold for large
quantities and a variety of APIs while maintaining their biological activity. Bioresorbable
electrospun materials can be degraded via natural metabolic processes and do
not require surgical removal post-implantation.
is a process of manufacturing non-woven fibrous materials where a high voltage
is applied to a probe connected to a polymer solution (which may contain an
API). Once a sufficient amount of charge has accumulated to break the surface
tension of the solution, a cone will form that allows for a liquid stream of
polymer to be ejected at a continuous rate towards a spool. This material is
then collected on the spool and can be used for downstream processing. Fibers
produced via electrospinning exhibit diameters on the submicron scale (µm),
causing these materials to have high surface area to volume ratios. Electrospun
materials have successfully been produced for biomedical purposes ranging from controlled-release
orally-dosed APIs, to wound healing applications.
Case study of
successful preclinical long-term drug delivery strategy: Cisplatin
strategies have been developed for increasing the therapeutic benefits of
certain APIs while decreasing their toxicity. Cisplatin is a highly toxic
chemotherapeutic agent commonly used to treat a variety of different cancers. Cisplatin
induces cell-death by causing non-specific DNA crosslinks to occur in not only
cancer cells, but also healthy cells. This, in turn, causes both on-target
regression of tumor cells, and several unwanted side effects that include
nausea, kidney damage, nerve damage, heart failure, and hearing loss. IV
administration of cisplatin results in high initial plasma drug levels which rapidly
decrease with a half-life of roughly thirty (30) minutes. These plasma
concentrations are contrasted with low tumor penetration, which limits the
potential overall benefit of the therapeutic intervention. An ideal
administration regimen of cisplatin would increase the tumor concentration of
the API to maximize chemotherapeutic effects while simultaneously decreasing
the plasma drug concentration to decrease unwanted side effects.
studies by Shikanov, et al., 2011 illustrate
this point. Using a bioresorbable polymer to control the delivery of cisplatin,
the study was able to significantly improve therapeutic outcomes in a mouse
model of bladder cancer while decreasing systemic exposure to the drug.
administration of cisplatin with the bioresorbable polymer directly into the
tumor resulted in a five (5)-fold increase in the maximum tolerated dose (MTD) compared
to systemic administration. In addition to increased tolerance of cisplatin,
significant improvements in therapeutic outcomes and API distribution were observed.
Local tumor injection of the bioresorbable excipient system resulted in 80% of
subjects remaining disease-free for forty (40) days (i.e., the remainder of the
study). This is in stark contrast to standard systemic administration of
cisplatin which resulted in exponential tumor mass growth after seven (7) days.
In line with the observed therapeutic benefits, local tumor administration of
the bioresorbable excipient system resulted in drug levels at the site of
administration over five-hundred (500) times higher than levels observed with
systemic administration. Additionally, reverse trends were observed in systemic
exposure where local tumor administration of the bioresorbable excipient system
resulted in an eighty (80)-fold decrease in plasma drug levels compared to
systemic administration. Together, this highlights the potential for
polymer/API excipient systems to maximize exposure to the desired site of
action, while simultaneously limiting systemic exposure to APIs and potentially
decreasing side effects.
offered by Poly-Med, Inc. as excipients for drug delivery:
Inc. (PMI), the leader in bioresorbable materials and medical device
development, is vertically integrated with design, development, and
manufacturing capabilities. PMI has a growing opportunity for providing
materials for drug delivery via PMI’s unique Viscoprene® technology. Electrospun materials are generated using a
combination of the Viscoprene® polymer that forms a
base depot for drug delivery with additional polymeric diluents/APIs. Once combined,
this drug delivery system can be injected through a standard Luer-Lok needle
and syringe to be administered into the desired anatomical location. Additionally,
PMI offers a catalog of Viscoprene® polymers, which allows
for tailoring of the release properties of the API to meet the necessary
clinical treatment schedule.
is able to offer medical device development for medical-grade electrospinning,
extrusion, additive manufacturing, and technical processes in a certified ISO
Class 8 environment. PMI facilities are certified to meet ISO: 13485:2016
standards for quality management of its design, development, and manufacturing
of bioresorbable polymers, fibers, sutures, medical textiles, and biomedical
products. Connect with PMI today to acquire more information about the Viscoprene® drug delivery
technology to customize the delivery of your active pharmaceutical ingredient
of interest by contacting firstname.lastname@example.org.