Polymer based Biohybrid Systems and

their Applications as Drug Delivery Systems

Prepared by:
Name File Number
Kamal Morkos 102177
Lama Mortada 102215
Mohamad Jawad Khalil 102202
Mohamad Salman Al Harakeh 102173
Rola Nasser 102221
Content:

Introduction …………………………………………………………………………………………………………………………. Page 2

Polymer selection ……………………………………………………………………………………………………………..…. Page 3

Biohybrid system design ………………………………………………………………………………………………………. Page 5

Characterization methods ……………………………………………………………………………………………………. Page 7

Drug delivery applications ……………………………………………………………………………………………………. Page 9

Challenges and Future Perspectives …………………………………………………..………………………………… Page 11

Conclusion …………………………………………………………………………………………………………………..………. Page 12

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 Introduction
A hybrid polymer is a material containing two or more different types of molecules, with at least one
of them being a polymer. A biohybrid system is obtained by the assembly of biopolymers such as
polypeptides, proteins, and polysaccharides of natural origin and other organic material.
Polysaccharides are utilized due to their versatility, easy handling, and low costs in addition to being
capable of forming a stable network of gels through cross linking reactions, here its importance is that
this process allows the incorporation of functional groups such as drug loaded nanocarriers, and
triggers which improves the effectiveness of the drug delivery system. While proteins are used for the
development of pharmaceutical delivery systems such as gelatin microparticles for the delivery of
large active biomolecules, or for the development of nanoparticles that are used to deliver drugs
intravenously.

These biohybrid systems combine the characteristics of their components resulting in a drug delivery
system (DDS) that can interact with a specific target within a specific tissue while minimizing the side
effects.

In the medical and pharmaceutical domains, these biomaterials are tested and used to develop
biosensors, scaffolds, and implants as well as being used in wound healing, tissue engineering, and as
drug delivery systems.The first lipid based drug delivery system described in scientific literature are
the liposomes.

As nanotechnology advanced, there was development of delivery systems which had improved
stability and better ability to encapsulate drugs (most notably hydrophobic drugs) such as solid lipid
nanoparticles (SLN) and nanostructured lipid carriers (NLC). In addition to lipospheres, and lipid
nanocapsules, with lipospheres being designed to deliver compounds by parenteral and topical routes,
exhibiting important anti-inflammatory effects in vivo.

The aim of these polymer based biohybrid systems is the delivery of drugs while overcoming the
barriers presented by traditional drug delivery systems.

These polymer based biohybrid systems can be used for spatiotemporal release of the drugs they
encapsulate.However, some of these polymer based biohybrid systems may be incapable to provide
properties such as adhesion, fixation, adequate consistency, and viscosity that are required for
multiple types of administration routes in which the preservation of the proper mechanical properties
of the polymeric system proves vital for the delivery of the active molecules to produce the
therapeutic effect.

The desired characteristics of these polymer based drug delivery systems are high specificity,
nontoxicity, physicochemical stability, protection of the drug from degradation, and ability to be
scaled-up and produced in high quantity. Therefore, biohybrid systems emerged as a versatile way for
the delivery of formulations and dosage forms with high specificity and minimal side effects.

This report will discuss the selection process of polymers while highlighting the desired properties, the
design of biohybrid systems with the selection criteria and the desired characteristics, the analytical
techniques used for the characterization of these polymer based hybrid systems, their drug delivery
applications while discussing their advantages over conventional drug delivery methods and specific
examples.And finally address the present challenges and limitations faced with polymer based
biohybrid systems as drug delivery systems while discussing strategies to overcome these difficulties,
as well as highlighting new trends and discussing future perspectives.

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 Polymer Selection
In biohybrid systems, the selection of polymers is crucial as they play a fundamental role in achieving
compatibility, functionality, and performance. The criteria for selecting polymers in biohybrid systems
depend on several factors, including the intended application, desired properties, and interactions
with biological components. Here are some key criteria to consider:

1. Biocompatibility: Polymers used in biohybrid systems should be biocompatible, meaning they

do not elicit adverse immune responses or toxicity when in contact with biological tissues or
fluids. Biocompatible polymers are typically non-toxic, non-inflammatory, and do not interfere
with cellular processes.
2. Mechanical properties: The mechanical properties of the polymer should be compatible with
the intended application. This includes considerations such as elasticity, flexibility, toughness,
and strength. For example, in tissue engineering, the polymer should have similar mechanical
properties to the target tissue to support proper cell attachment, growth, and function.
3. Degradation characteristics: Depending on the application, polymers may need to degrade
over time to allow for tissue regeneration or to facilitate the release of drugs or biomolecules.
The degradation rate should match the desired timeline for the specific application. Some
polymers degrade through hydrolysis, enzymatic processes, or other mechanisms, and the
degradation byproducts should be non-toxic.
4. Stability: Polymers used in biohybrid systems should be stable under physiological conditions
to ensure the longevity and reliability of the system. They should not undergo significant
degradation or chemical changes that could compromise their structural integrity or
functionality over time.
5. Functional groups and surface properties: Polymers can be modified or functionalized with
specific chemical groups to enable interactions with biological molecules or enhance cell
adhesion. For example, the presence of reactive functional groups (e.g., amine or carboxyl
groups) can facilitate the attachment of bioactive molecules, such as peptides or growth
factors.
6. Processing and fabrication: The polymer should be processable using techniques suitable for
the desired biohybrid system fabrication, such as casting, molding, electrospinning, or 3D
printing. Processability considerations include solubility, melt processing, viscosity, and the
ability to form stable structures.
7. Biofunctionalization and bioconjugation: Polymers should allow for the attachment or
incorporation of bioactive molecules, such as proteins, enzymes, antibodies, or nucleic acids,
to confer specific biological functions to the biohybrid system. The polymer should support
bioconjugation techniques without compromising the stability or functionality of the attached
molecules.
8. Cost and availability: The cost and availability of the polymer should be taken into account,
especially for large-scale or commercial applications. Some polymers may be expensive or
difficult to source, limiting their practical use in biohybrid systems.

Polymers play a crucial role in drug delivery applications, where they serve as carriers or
vehicles for therapeutic agents. Several desirable properties of polymers make them well-
suited for drug delivery systems, including biocompatibility, biodegradability, controlled
release characteristics, and ease of synthesis.

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Biocompatibility: In drug delivery applications, it is essential for polymers to be biocompatible to
minimize any adverse effects on the body. Biocompatible polymers do not induce significant immune
responses, inflammation, or toxicity when in contact with biological tissues or fluids. This ensures the
safety and compatibility of the drug delivery system within the biological environment.

Biodegradability: Polymers with biodegradable properties can undergo degradation over time, either
through hydrolysis, enzymatic processes, or other mechanisms. This is beneficial for drug delivery
systems as the polymer can gradually break down, releasing the drug payload in a controlled manner.
Biodegradable polymers eliminate the need for surgical removal or extraction, making them
advantageous for sustained drug release and reducing the potential for long-term accumulation in the
body.

Controlled release characteristics: Polymers used in drug delivery systems should possess the ability
to control the release rate and duration of the encapsulated drug. This enables precise administration
and sustained therapeutic effect. By modifying the polymer's structure, such as adjusting its molecular
weight, crosslinking density, or incorporating specific chemical moieties, the release kinetics can be
tailored to achieve desired profiles, such as zero-order, sustained, or pulsatile release.

Ease of synthesis: Polymers suitable for drug delivery applications should be readily synthesized using
established and scalable methods. Ease of synthesis allows for efficient production, cost-effectiveness,
and reproducibility of the drug delivery system. Furthermore, the polymer synthesis should allow for
the incorporation of drug molecules during the manufacturing process, ensuring efficient drug
encapsulation.

There are just a few examples of commonly used polymers in biohybrid systems, each with its own
advantages. The selection of the polymer depends on the specific requirements of the application,
such as biocompatibility, degradation characteristics, mechanical properties, and the desired
interaction with biological components.

Polyethylene Glycol (PEG): Advantages: PEG is highly biocompatible, non-toxic, and has excellent
water solubility. It can be easily modified to introduce specific functional groups for bioconjugation,
enhancing its versatility in biohybrid systems. PEG is also known for its "stealth" properties, reducing
immunogenicity and prolonging the circulation time of bioconjugates.

Polylactic Acid (PLA): Advantages: PLA is a biodegradable and biocompatible polymer derived from
renewable sources. It offers good mechanical strength and controlled degradation, making it suitable
for tissue engineering and drug delivery applications. PLA degrades into non-toxic lactic acid, which
can be metabolized and eliminated by the body.

Poly(lactic-co-glycolic acid) (PLGA): Advantages: PLGA is a copolymer of lactic acid and glycolic acid,
combining the benefits of PLA and polyglycolic acid (PGA). It exhibits excellent biocompatibility,
biodegradability, and tunable degradation rates. PLGA can be easily processed into various forms,
including nanoparticles, microspheres, and scaffolds, enabling controlled drug release and tissue
regeneration.

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 Biohybrid System Design
Designing polymer-based biohybrid systems involves careful consideration of several key principles
and strategies. Some of the important design principles and strategies for constructing such systems:

1. Biomimicry: Biohybrid systems often aim to mimic the structure, function, or properties of
natural biological systems. The design principles of biomimicry involve studying and
replicating the key features of biological systems, such as hierarchical organization, cellular
interactions, or specific functionalities. Polymer-based biohybrid systems can be designed to
mimic extracellular matrices, cellular environments, or specific tissues to enhance
compatibility and functionality.
2. Rational Polymer Selection: Selecting the appropriate polymer(s) is a critical step in biohybrid
system design. Polymers should possess the desired properties, such as biocompatibility,
biodegradability, mechanical strength, and the ability to interact with biological components.
The choice of polymer can be based on factors such as the target application, desired release
kinetics, and the specific interactions required with cells, proteins, or other biomolecules.
3. Surface Modification: Surface modification of polymers is commonly employed to enhance
the bioactivity and interactions of the biohybrid system. Functional groups can be introduced
onto the polymer surface to facilitate cell adhesion, bioconjugation of biomolecules, or the
incorporation of specific receptors. Surface modification techniques include chemical
functionalization, plasma treatment, or the use of self-assembled monolayers.
4. Controlled Drug Release: Polymer-based biohybrid systems are frequently used for drug
delivery applications. The design should focus on achieving controlled and sustained drug
release profiles. This can be accomplished through the incorporation of drug-loaded polymer
matrices, micro/nanoparticles, hydrogels, or stimuli-responsive systems. Strategies such as
adjusting polymer degradation rates, encapsulation techniques, or surface modifications can
be employed to achieve desired release kinetics.
5. Multifunctionality and Integration: Biohybrid systems often require multiple functionalities to
perform complex tasks. Polymers can be engineered to incorporate various components, such
as drug reservoirs, targeting ligands, imaging agents, or sensors, within a single system.
Integration of multiple functionalities into a single polymer-based construct allows for
synergistic effects, improved efficiency, and enhanced therapeutic outcomes.
6. Biodegradability and Clearance: For applications involving temporary or implanted biohybrid
systems, the design should consider the biodegradability and clearance of the polymer.
Biodegradable polymers can be tailored to degrade at controlled rates, enabling them to
provide therapeutic functions while gradually resorbing within the body. This minimizes the
need for invasive removal procedures and reduces long-term complications.
7. Manufacturing and Scalability: Consideration of manufacturing processes and scalability is
crucial to translate polymer-based biohybrid systems from research to clinical or commercial
applications. Design strategies should ensure that the fabrication methods are reproducible,
scalable, and cost-effective. Techniques such as 3D printing, electrospinning, or microfluidics
can be employed to achieve precise and scalable fabrication.

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Incorporating biological components, such as proteins, peptides, and cells, into the polymer matrix of
drug delivery systems can enhance drug delivery efficiency and specificity in several ways:

1. Targeting Ligands: Biomolecules, such as antibodies, peptides, or aptamers, can be conjugated

or incorporated onto the polymer surface to serve as targeting ligands. These ligands can
recognize specific receptors or markers on target cells or tissues, promoting selective binding
and internalization of the drug-loaded polymer carrier. Targeting ligands enhance the
specificity of drug delivery, allowing for localized therapy and reducing off-target effects.
2. Bioactive Signaling Molecules: Bioactive molecules, such as growth factors, cytokines, or
enzymes, can be incorporated into the polymer matrix to provide signaling cues and enhance
therapeutic efficacy. These molecules can regulate cellular responses, stimulate tissue
regeneration, or modulate immune reactions, promoting desired therapeutic outcomes.
3. Cell Encapsulation: Cells, such as stem cells or genetically modified cells, can be encapsulated
within the polymer matrix to exert their therapeutic effects. The polymer protects the cells
from the immune system, provides a controlled microenvironment, and facilitates their
prolonged presence at the site of action. Encapsulated cells can release bioactive factors or
perform specific functions, such as producing therapeutic proteins, promoting tissue
regeneration, or modulating the immune response.
4. Protein/Peptide Delivery: Proteins or peptides with therapeutic potential can be incorporated
within the polymer matrix to enhance their stability, controlled release, and targeted delivery.
The polymer protects the proteins/peptides from degradation or denaturation and allows for
sustained release over time. This ensures the therapeutic molecules reach the target site in
an intact and effective form.

Synthesis and fabrication techniques play a crucial role in the development of biohybrid systems. Here
is a brief explanation of three commonly used techniques:

1. Encapsulation: Encapsulation involves entrapping bioactive molecules, such as drugs,

proteins, or cells, within a protective polymer matrix or carrier. Techniques like
emulsion/solvent evaporation, coacervation, or electrostatic assembly are used to
encapsulate the bioactive components. Encapsulation provides controlled release, protection
from degradation, and targeted delivery of the encapsulated entities.
2. Surface Modification: Surface modification techniques alter the surface properties of
polymers to enhance their bioactivity, biocompatibility, or interaction with biological
components. Common methods include chemical grafting, plasma treatment, or self-
assembled monolayer deposition. Surface modification enables the introduction of functional
groups, biomolecules, or coatings onto the polymer surface, facilitating targeted cell
adhesion, bioconjugation, or controlled release.
3. Self-Assembly: Self-assembly is a process where molecules or nanoparticles spontaneously
organize into ordered structures or patterns. In biohybrid systems, self-assembly can be
employed to create functional nanostructures or scaffolds. Techniques such as
nanoprecipitation, micelle formation, or electrostatic assembly utilize molecular interactions
to drive the self-assembly process. Self-assembled structures offer controlled release,
increased stability, and enhanced interactions with biological systems.

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 Characterization Methods
Characterizing polymer-based biohybrid systems is crucial for understanding their structure,
morphology, composition, and properties. Several analytical techniques are commonly employed for
this purpose. Here is a brief overview of some key techniques used for the characterization of polymer-
based biohybrid systems:

Microscopy:

Electron Microscopy (SEM and TEM): Scanning Electron Microscopy (SEM) and Transmission Electron
Microscopy (TEM) provide high-resolution imaging of the biohybrid system's morphology, surface
features, and internal structure.

Atomic Force Microscopy (AFM): AFM allows for imaging at the nanoscale and provides information
about surface topography, roughness, and mechanical properties of the biohybrid system.

Spectroscopy:

Fourier Transform Infrared Spectroscopy (FTIR): FTIR analyzes the functional groups present in the
biohybrid system, providing information on chemical composition, molecular structure, and
interactions.

Nuclear Magnetic Resonance (NMR): NMR spectroscopy offers insights into the chemical structure,
molecular dynamics, and interactions within the biohybrid system, particularly in terms of polymer
chain conformation and mobility.

UV-Vis Spectroscopy: UV-Vis spectroscopy helps determine the optical properties, such as absorbance
and transparency, of the biohybrid system, which can be indicative of its composition and structure.

Thermal Analysis:

Differential Scanning Calorimetry (DSC): DSC measures the heat flow associated with thermal
transitions, such as melting or glass transition, providing information about the thermal properties,
crystallinity, and phase transitions within the biohybrid system.

Thermogravimetric Analysis (TGA): TGA measures the weight changes of the biohybrid system as a
function of temperature, providing insights into its thermal stability, decomposition behavior, and
composition.

Particle Size and Zeta Potential Analysis:

Dynamic Light Scattering (DLS): DLS measures the size distribution of particles or aggregates within
the biohybrid system, providing information on particle size, stability, and colloidal properties.

Zeta Potential Analysis: Zeta potential measurements assess the surface charge and electrostatic
interactions within the biohybrid system, which can influence its stability, dispersion, and cellular
interactions.

These two analytical techniques, among others, enable researchers to investigate the structural,
compositional, and physical properties of polymer-based biohybrid systems. By employing a
combination of these techniques, a comprehensive understanding of the biohybrid system's
characteristics can be achieved, aiding in the optimization of its performance and functionality.

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Understanding the physicochemical properties and structural features of biohybrid systems is of
paramount importance for optimizing drug delivery performance. Here are key reasons why this
understanding is crucial:

1. Stability and Shelf-Life: Knowledge of the physicochemical properties allows for the design
and formulation of stable biohybrid systems with a longer shelf-life. Understanding factors
such as solubility, compatibility between components, and physical stability helps prevent
aggregation, degradation, or loss of activity over time.
2. Drug Loading and Release: The physicochemical properties of the biohybrid system directly
impact drug loading capacity and release kinetics. By understanding factors such as drug-
polymer interactions, solubility, diffusion rates, and encapsulation efficiency, optimal loading
and controlled release profiles can be achieved. This knowledge ensures efficient delivery of
the therapeutic agent to the target site while maintaining therapeutic efficacy.
3. Targeting and Specificity: Physicochemical properties influence the ability of biohybrid
systems to target specific cells, tissues, or organs. Properties such as surface charge, size, and
surface functionalization impact the system's interaction with biological components,
enabling targeted delivery and enhancing specificity. Understanding these properties aids in
designing biohybrid systems that can navigate biological barriers and selectively accumulate
at the desired site of action.
4. Biocompatibility and Safety: The physicochemical properties of biohybrid systems are crucial
for ensuring biocompatibility and safety. Factors such as surface charge, hydrophobicity, and
degradation profiles influence the interactions of the system with biological environments,
including cells, tissues, and the immune system. Understanding these properties helps
minimize adverse reactions, cytotoxicity, and immunogenicity, enhancing the safety and
acceptance of the biohybrid system.
5. Pharmacokinetics and Pharmacodynamics: Physicochemical properties play a key role in
determining the pharmacokinetics and pharmacodynamics of the biohybrid system.
Parameters such as particle size, shape, surface area, and surface chemistry affect the
system's biodistribution, circulation time, cellular uptake, and therapeutic efficacy.
Understanding these properties enables tailoring the biohybrid system to achieve the desired
pharmacokinetic profiles and therapeutic outcomes.

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 Drug delivery Applications

The field of drug delivery has been transformed by the development of polymer-based biohybrid
systems, which combine polymers with biological components. Some of the key drug delivery
applications of polymer-based biohybrid systems:

1. Nanoparticles: Polymer-based nanoparticles are widely used for drug delivery due to their
small size and high surface area. They can be designed to encapsulate both hydrophobic and
hydrophilic drugs within their polymer matrix, protecting the drug from degradation and
improving its stability. Nanoparticles can also be surface-functionalized with targeting ligands
to enhance specific drug delivery to desired tissues or cells.
2. Hydrogels: Polymer-based hydrogels are three-dimensional networks that can absorb and
retain large amounts of water. They are used as drug delivery systems due to their high water
content and biocompatibility. Hydrogels can be loaded with drugs and implanted at specific
sites in the body for sustained drug release over an extended period. They are particularly
useful for local delivery to treat various diseases, such as cancer, inflammation, and wound
healing.
3. Micelles: Polymer-based micelles are self-assembled structures formed by amphiphilic block
copolymers. They have a core-shell structure, with a hydrophobic core and a hydrophilic shell.
Micelles can solubilize hydrophobic drugs in their core, improving their bioavailability and
circulation time. The hydrophilic shell provides stability and allows for controlled release of
the encapsulated drug.
4. Liposomes: Polymer-based liposomes are lipid bilayer vesicles that can encapsulate both
hydrophobic and hydrophilic drugs within their aqueous core. Polymer coating of liposomes
can enhance their stability and improve drug retention, resulting in prolonged circulation time
and controlled drug release.
5. Nanogels: Polymer-based nanogels are cross-linked polymer networks that can encapsulate
drugs within their porous structure. They combine the advantages of nanoparticles and
hydrogels, offering high drug loading capacity, stability, and controlled release. Nanogels can
respond to external stimuli such as temperature, pH, or enzymatic activity, enabling triggered
drug release at specific sites in the body.
6. Polymer-protein conjugates: Polymer-based bioconjugates, where polymers are covalently
attached to proteins or peptides, have gained attention for drug delivery applications. These
conjugates can improve the stability, bioavailability, and pharmacokinetics of therapeutic
proteins, peptides, and antibodies. They can protect the protein from degradation, extend its
circulation time, and enhance its cellular uptake.

Biohybrid systems have several advantages over conventional drug delivery methods:

1. Enhanced Drug Stability: They protect drugs from degradation, ensuring their integrity and
bioactivity.
2. Prolonged Release Kinetics: Biohybrid systems enable controlled and sustained drug release,
optimizing treatment efficacy.
3. Targeted Delivery: They can actively or passively target specific tissues, reducing off-target
effects and enhancing drug concentration at the desired site.
4. Improved Bioavailability: They enhance drug solubility, increasing drug bioavailability and
absorption.
5. Stimuli-Responsive Release: They can respond to specific stimuli, triggering drug release at the
desired location or under specific physiological conditions.

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 6. Versatile Formulations: Biohybrid systems offer flexibility in formulation, allowing
customization for different drugs and delivery modes.
7. Combination Therapies: They can accommodate multiple therapeutic agents, enabling
synergistic combination therapies.

Examples of biohybrid systems used for delivering different types of therapeutics:

1. Small Molecule Drugs: Polymeric nanoparticles and liposomes are employed to encapsulate
and protect small molecule drugs, such as anticancer agents like paclitaxel and doxorubicin.
2. Nucleic Acids: Cationic polymers and lipid-based systems, like lipid nanoparticles (LNPs), are
used for efficient delivery of nucleic acids, including mRNA-based COVID-19 vaccines.
3. Proteins: Protein-loaded hydrogels and polymer-protein conjugates improve stability and
extend circulation time for growth factors, cytokines, and therapeutic enzymes.
4. Peptides: Peptide-loaded nanoparticles and self-assembled peptide nanofibers offer
protection and controlled release of therapeutic peptides.

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 Challenges and Future Perspectives
Polymer biohybrid-based drug delivery has become one of the promising delivery systems for many
diseases like cancer, inflammatory bowel diseases.

The main problem associated with conventional drug delivery systems is the resistance developed by
tumor cells. So as to overcome this problem, microbial drug therapy in combination with an anti-
cancer agent plays an important role in the drug delivery system. Moreover, other strategies to treat
tumor cells include bacterial ghosts, microbots and bactofection. Even if microbial therapy shows
favorable applications, toxicity, dose and therapeutic efficacy still remain a problem.

Another novel approach is virotherapy, which includes using the virus, virosomes, viral particles, to
convey molecules, nucleic acids, biological actives, etc. Bacteria show promising results because of
their exploited properties like penetration in the tumor, increase in immunity, etc. Bacteria in drug
delivery are extensively under research and achieved success in preclinical trials as well as in clinical
trials. A novel approach of microbes-based drug delivery with reduced toxicity and side effects will
surely be a futuristic advanced carrier to actively improve patients' health.

The idea that a single nanosystem will satisfy all needs for drug delivery is utopian. Although
pharmaceutical nanotechnology has advanced, all of the current drug delivery system (DDS) have
benefits and restrictions for clinical usage. The DDS made up only of biopolymers may have
unfavorable mechanical characteristics and lack the benefits of drug encapsulation. The therapeutic
qualities of protein nanoparticles and liposomes are impacted by their limited physicochemical
stability, which can also occur in emulsions, despite their ability to encapsulate hydrophilic molecules.
Long-term stability and poor hydrophilic molecule encapsulation efficiency are characteristics of SLN
and NLC. Due to unsatisfactory adhesion, spreadability, and viscosity, which are benefits of emulsions,
CD and all colloidal compositions cannot be successfully administered for topical routes.

Finally, both hydrophilic and hydrophobic compounds can be included in the structures of CD and
liposomal systems. Given that there is no ideal DDS system, selecting the best device requires a
thorough knowledge of the structural, physicochemical, and biological characteristics of the route and
medication.

The use of (bio)polymeric excipients in biohybrid systems development is especially relevant due to
its:
1. Diversity
2. Abundance
3. Low cost
4. Biocompatibility

This class of biohybrid systems (organic-organic) deserves attention, considering the ability to interact
with the ability to interact with sites of interest, predicting and controlling the DDS performance when
in contact with the target, solving several limitations of traditional DDS.

There are several hybridization processes of DDS currently employed to improve the nanocarrier
specificity to the targets. Changes in the global charge of the traditional nanocarriers by superficial
functionalization or isomerization provide hybrid smart drug delivery systems, which are able to
electrostatically interact with the different mucosal tissues, fixing them at the desired site.

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Moreover, molecular designed polymer-based hybrid DDS can combine several stimuli-dependent
effects in a single biodevice, such as pH and temperature, which should be specific to the action site,
as a tumor tissue.

Along with that, the regulatory issues of the excipients' safety as well as their conjugation in a single
nanostructured biodevice are not fully established, contributing to the delay in commercial availability
of these promising DDS. Moreover, the long-term consequences of nanostructured systems as DDS in
the environment have not been fully elucidated yet.

Conclusion:

In conclusion, the research into polymer based biohybrid systems as drug delivery systems
has been developed and studied extensively over the past few years. This report went over essential
topics and key points regarding the development of polymer based biohybrid systems intended for
drug delivery. Starting with the polymer selection process, which is a first and vital step, as these
polymers constitute the building blocks of the delivery systems. Then discussing the design of the
biohybrid system which involves the careful consideration of key principles which provide the
foundation for the construction of the polymer based system where these design principles and
strategies provide a foundation for constructing polymer-based biohybrid systems with improved
biocompatibility, functionality, and performance. After which the characterization methods are
expanded upon, detailing the various analytical methods used for understanding the structure and the
morphology of the polymer. Moreover, the drug delivery applications of the mentioned systems are
tackled, with the advantages of these polymer based systems over traditional dosage forms talked
about. And lastly, the challenges and limitations associated with this dosage form are discussed, while
also expanding on potential future perspectives regarding this technology, demonstrating the
potential of polymer based biohybrid systems as versatile and effective drug delivery platforms
characterized by improved biocompatibility, functionality, and performance.

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 Writer(s) of the section:

Introduction Kamal Morkos

Polymer Selection Mohamad Salman Al Harakeh

Biohybrid System Design Mohamad Jawad Khalil

Characterization Methods Mohamad Jawad Khalil & Mohamad Salman Al Harakeh

Drug Delivery Applications Rola Nasser

Challenges and Future Perspectives Lama Mortada

Conclusion Kamal Morkos

References:

● Advances in Hybrid Polymer-based Materials for Sustained Drug Release

https://www.hindawi.com/journals/ijps/2017/1231464/

● Chen, Y., and Zhang, Z. (2019). Polymers for bio hybrid systems: from synthetic
polymers to natural polymers. Journal of Materials Chemistry B, 7(5), 701-713.

● Biomater Res. 2020; 24: 12. Published online 2020 Jun 6. doi: 10.1186/s40824-020-
00190-7 PMCID: PMC7285724 PMID: 32537239. Recent advances in polymeric drug
delivery systems.

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