Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5632_Библиотеки_им_академика_М_И_Перельмана.pdf
376 C. Chapa
offers a rigid crystalline structure in the shape of a double pyramid with six sides
(hexagonal bipyramidal) whose formula is represented as Ca
(PO4)3OH. The first formula option indicates the presence of ten calcium ions
Ca
5
2+
(Ca
) in each unit cell, while the second is the reduction to the minimum expression
(PO4)6(OH)2 or
10
but always keeps a precise ratio of calcium and phosphorus atoms (Ca/P) within the
crystalline unit cell, which in this case is 1.67 (10:6). If this ra
ideal value, the
crystal structure becomes less stable and dissolves more easily.
tio deviates from the
Interestingly, hydroxyapatite with a slight calcium deficiency (Ca/P ratio of 1.60)
shows slightly better bioactivity compared to the perfect ratio material (Ca/P 1.67).
The basic composition of the mineral component of bone is hydroxyapatite whose
formula Ca
(PO4)6(OH)2. In addition to containing calcium and phosphate, it also
10
contains minimal proportions of sodium, chlorine, carbonates, and magnesium,
which act
in the remodeling of the bone. Hydroxyapatite is part of the apatite family,
has a hexagonal structure, with a space group P63/m and has a Ca:P ratio of 1.67.
The crystal structure of the material has a six-fold symmetry along a specific axis
(c-axis) and three identical axes (a-axes) arranged perpendicularly at 120 degrees to
each other. Unit cell dimensions for this crystal structure are reported to be
0.9422 nm for bo
common methods
th a and b axes, and 0.688 nm for the c-axis. There are several
used to create this material, including wet chemical precipitation,
sol-gel, hydrothermal, and microwave irradiation.
15.2.1 Biomedical Applications of Hydroxyapatite
Bone tissue is a specialized connective tissue that, unlike other tissues, is
mineralized. This mineralization gives the bone the ability to provide support and
protection. The extracellular matrix of the tissue is composed of the organic matrix
and the inorganic matrix. The organic matrix represents 90% of type I collagen and
to a lesser extent type IV collagen. The other 10% is represented by the fundamental
substance, which are other non-collagen proteins such as: proteoglycan
macromolecules such as hyaluronan, chondroitin sulfate and keratan sulfate; multiadhesive glycoproteins such as osteonectin, sialoproteins; vitamin K-dependent
proteins such as osteocalcin, and finally, growth factors and cytokines, the most
important being bone morphogenic proteins (BMPs).
There are
four types of cells that can be found in bone. Osteoprogenitor cells are
cells derived from mesenchymal stem cells that give rise to osteoblasts. Osteoblasts
are derived from mesenchymal stem cells whose function is to secrete the extracellular matrix that, when surrounded by it, is called osteocyte and stops secreting
matrix, becoming one of those responsible for the viability of bone tissue.
Osteoclasts are bone resorption cells present on bony surfaces where bone is being
removed or remodeled (rearranged) or where bone has been injured. One tissue is
classified into two distinct structural organizations: compact and spongy. Compact
bone tissue is a dense, compact layer, which forms the outer surface of the bone. This
comprises 80% of the bone mass and is covered by the periosteum and lined up by
the endosteum. Cancellous bone tissue comprises 20% of the bone mass and forms
15 Hydroxyapatite-Starch-Based Sustainable Biomaterials 377
the inner part of the bone with thin web-like tissue spicules and is lined only by the
endosteum. Compact and spongy bone tissue, in turn, presents a structural organization compo sed of osteons on a micrometer scale that have a central duct called
Havers’ duct that contains vessels and nerves where the extensions of the osteocytes
arrive to carry out an exchange of substances. Each osteon is made up of concentric
lamellae and these in turn are made up of collagen fi bers on a nan
collagen fiber is
will be made that will serve as nucleation sites for the hydroxyapatite crystals.
Bioactivity pertains to the capability of bone scaffolds to establish a direct bond
with the surrounding bone, avoiding the formation of fibrous tissue. The evaluation
of bioactivity commonly involves testing the biomaterial’s potential to form apatite
in a simulated body fluid (SBF), which has ion concentrations similar to human
blood plasma. A material is considered bioactive if it enhances apatite crystallization
in a hydroxyapatite-supersaturated solution. However, the reliability of using in vitro
SBF tests to predict a material’s bioactivity in vivo has been debated, as Bohner and
Lemaitre showed that “in vitro bioactivity” tests in SBF solutions cannot be used to
predict the in vivo bone bonding ability of a material.
Scientists can produce HA using various methods, including chemical precipitation and electrospinning. This unique material holds promise for several biomedical
applications due to its biocompatible and bioactive properties. It can function as an
implant material to promote bone regeneration, a carrier for delivering drugs, and
even a system for gene delivery. When processed into tiny particles, hydroxyapatite
can be used to create materials for bone tissue engineering. These particles degrade
slowly within the body (biodegradable) and have excellent properties for encouraging bone growth (osteoconductive and osteoinductive). HAnanoparticles modified
with a special compound (poly(sodium 4-styrene sulfonate)) can act as carriers for
antibiotics like vancomycin. This allows for controlled release of the medication
after implantation of a bone scaffold. Another environmental contribution of
hydroxyapatite microspheres is that they have a high capacity to absorb heavy
metals thanks to their porosity. For this reason, several researchers use them to
study and apply them in waters contaminated with these harmful elements and other
pollutants.
in turn made up of collagen fibrils where specific attachment points
ometer scale. Each
15.2.2 Hydroxyapatite Composites and Their Application in Drug
Delivery
Its biocompatibility and ability to induce bone formation has already been more than
demonstrated. However, hydroxyapatite has been emerging as a strategic component
in some drug delivery systems and we are seeing it alone or in combination with
polymers. Recent research promotes various methodologies where hydroxyapatite is
used and that is related to the controlled administration of drugs. Researchers take
advantage of its properties to propose solutions to improve the efficacy and reduce
the side effects of some pharmacological treatments.
378 C. Chapa
Where we see a very significant advance is the use of particle formulations for
dental disinfectants. Recently, the manufacture of calcium phosphate particles with
immobilized ciprofloxacin was carried out by a coprecipitation process. In this
process, the aging time significantly influences the physicochemical properties of
the resulting particles. Interestingly, particles with higher ciprofloxacin content
showed a slower release of the drug in physiological saline solutions in a less soluble
crystalline matrix of hydroxyapatite, compared to amorphous particles. Both types of
particles demonstrated antibacterial and acid-neutralizing activities against important oral bacteria such as Streptococcus mutans and Porphyromonas gingivalis (Pal
et al.
2024). In the same sense, hydroxyapatite microspheres exhibit defects in
mechanical properties, such as low resistance and brittleness, but have a large
specific surface area and good injection properties. In addition, these microspheres
can carry proteins and bioactive factors, as well as drugs to facilitate bone or dental
regeneration. Consequently, it is foreseeable that the preparation of microspheres
composed in this way will be suitable for such clinical applications (Wang et al.
2024).
Hydroxyapa
s prepared in other presentations, for example, in another study
tite i
hydroxyapatite nanorods were prepared for the release of bumetanide and
meloxicam, these active ingredients are poorly soluble in water. The method used
on this occasion was known as hydrothermal synthesis. Compared to compounds
alone, hydroxyapatite helped improve drug dissolution, solubility, and wettability
rates. Precisely this hybrid system is a good example of how hydoxoapatite improves
desirable properties in drug delivery (Friuli et al. 2024). In addition, hydroxyapatite
was shown to be effective in improving the bioavailability and tissue distribution of
nicotinamide mononucleotide (NMN) that was incorporated into the delivery system. In the same way as an example described above, here the chemical precipitation
method was used to obtain nanoparticles and NMN was incorporated by physical
adsorption. Again, the hydroxyapatite system showed signi ficantly slower release
compared to free NMN. This time, hydroxapatite extended circulation time,
improved bioavailability, and raised plasma levels of NMN, and NAD+, with
specific distribution in tissues such as the brain and liver in in vivo studies (Zhang
et al. 2023)
Another compo
.
und that has been involved in demonstrating that hydroxyapatite
contributes in the field of nanomedicine is chloroaluminum phthalocyanine
(ClAlPc). On this occasion, the method for synthesizing hydroxyapatite
microspheres was using vaterite as a template and the drug was encapsulated by
mixing the components. Notably, the encapsulation efficiency was confirmed with
photophysical and photobiological studies. The results showed a significant reduct
in cell viability of gliosarcoma cells treated with photodynamic therapy
ion
(Ambrosio et al. 2023). Even bioactive compounds such as allicin, derived from
garlic, which has shown beneficial effects on dyslipidemia, obesity, endothelial
dysfunction, hypertension, heart attack, heart disease and even on cardiac arrhythmia, can also be loaded on hydroxyapatite. In one study, the biomaterial was shown
to contribute to the improved antibacterial properties and controlled release of allicin
(Bose et al. 2022).
15 Hydroxyapatite-Starch-Based Sustainable Biomaterials 379
As can be seen, hydroxyapatite, in its various forms, is being consolidated as a
component in the formulation of nanom edicine systems for drug delivery. Its
biocompatibility and ability to improve the bioavailability of medicines, along
with its applicability in bone and tooth regeneration, make it a versatile and effective
option in modern medicine. Recent studies highlight its potential in creating
sustained-release systems, offering new prospects for the development of more
effective and targeted treatments. When combined with polymeric materials, such
as starch, it gives rise to potential applications ranging from tissue engineering,
photodynamic therapy, to enhanced drug delivery (Mahdavinia et al.
et al. 2022).
2019; Ahamed
15.3 Starch
15.3.1 Sources, Structure and Properties of Starch
Plants store energy in the form of complex carbohydrates, particularly starch. These
starch molecules are very attractive to water because they have numerous hydroxyl
groups that can form hydrogen bonds with water molecules. Starch is especially
abundant in underground stems (tubers) like potatoes and in seeds (Mweta et al.
2010; Hong et al. 2011). Starch itself is a combination of two different types of
glucose polymers: amylose and amylopectin. Amylose is a long, unbranched chain
of sugar molecules (glucose) linked together in a specific way. These chains can vary
greatly in size. Amylopectin, on the other hand, is much more complex. It’s also a
large molecule, but unlike amylose, it’s highly branched. The branches occur at
regular intervals along the main chain. The macromolecules that make up starch
grains are arranged in layers. Amylose and amylopectin are two distinct polymer
structures that make up starches. Most starches contain 80% amylopectin and 20%
amylose. Amylose molecules, found in the inner layers, are helically wound chains,
made up of between 200 and 20,000 moles of glucose linked by glycosidic bonds
1–4. In the outer layer is amylopectin, which is structured differently from amylose.
The amylopectin molecule contains diglycan bonds 1–4 and 1–6. The glucose
molecules in the amylopectin skeleton are connected to each other by glycosidic
bonds. Backbone branching is common and arises from the coupling of 1–6glycosides with additional glucose molecules. In branches, endpoints account for
4–5% of total links.
15.3.2 Biomedical Applications of Starch
The pharmaceutical preparations use starch as an excipient in a variety of forms,
including as a disintegrant, binder, absorbent, viscosifier, diluent, and slipping agent.
It is commonly used as a thinner in face powders, as an absorbent in talcum powders,
and as an emulsion stabilizer in the cosmetic industry. Starch is also being studied as
a food packaging material (García-Guzmán et al. 2022 ) and derivatives (Azfaralariff
380 C. Chapa
et al. 2020; Chen et al. 2020; Sathyan and Nisha 2022). The search for new sources
of this carbohydrate that allow it to achieve different functional qualities is inspired
by the varied properties of starch. Starch has become a starter material for the
creation of excipients with new capabilities due to its biodegradability, biocompatibility, and bioavailability.
The use of starches as carriers of active molecules has been studied to find
alternative approaches to the problems of minimizing the side effects of certain
active molecules, protecting them from harmful environmental factors, transporting
them to the site of action and doing so in a regulated manner, as well as meeting the
need to use biodegradable and biocompatible materials as excipients. Starches have
been used in the development of encapsulation techniques for this purpose.
15.4 Rationale for Combining HA and Starch: Creation
of Sustainable Green Biomaterials with Enhanced
Functionalities
HA in combination with starch has emerged with the aim of creating sustainable
green biomaterials with enhanced functionalities that fulfill the functions of bone
both at the cellular and structural level for bone replacement or repair (Miculescu
et al.
2017; Koski et al. 2018; Ordon et al. 2019; Mohd Roslan et al. 2021; You et al.
2022; Le et al. 2023; Murugan and Akshata 2023), and for other important biomedi-
cal applications such as drug delivery. Nanomedicine, as a multi- and interdisciplinary research area, has made it necessary to search for materials and techniques that
meet the different requirements for the creation of a sustainable biomaterial, so the
following points need to be considered:
(a) Biocompatibility. Materials that do not trigger an immune or cytotoxic response
are needed.
(b) Porosity. A porous structure promotes tissue growth and nutrient exchange. Pore
size of 50–100 microns is essential for the growth of bone tissue.
(c) Osteoinductivity. The support must be able to allow the process of recruitment
and differentiation of stem and osteoprogenitor cells.
(d) Biodegradability. Materials that have resorption rates that go hand in hand with
bone formation should be used.
(e) Mechanical properties. The support must offer adequate mechanical strength to
maintain the integrity of the support, and it has been shown that trying to mimic
the mechanical properties offers better differentiation of osteogenic cells.
Surface proper
(f)
morphological. Having similar morphologi cal properties will allow the migration process of osteo genic cells to the new matrix. The chemical properties will
allow the cells to adhere to the matrix.
ties. There are two that are fundamental for cells: chemical and
15 Hydroxyapatite-Starch-Based Sustainable Biomaterials 381
All these demanding requirements for a sustainable biomaterial that is used in
applications as sophisticated as drug delivery are met by designing and obtaining
biomaterials that combine hydroxyapatite with starch.
HA-starch compo sites exhibit excellent biocompatibility, making them suitable
for biomedical applications. HA, being similar to the mineral component of bone, is
inherently biocompatible and supports bone cell attachment and proliferation.
Starch, being a natural polysaccharide, is also biocompatible and biodegradable.
The combination of these materials creates a compo site that integrates well with
human tissues, promoting cellular activities essential for bone healing and regeneration. Moreover, the degradation products of starch are non-toxic and can be
metabolized by the body, further enhancing the composite’s compatibility.
15.5 Synthesis Techniques for HA-Starch Composites
Sustainable biomaterial manufacturing techniques constitute a significant factor in
the biomedical function. The morphology of the material is essential for the release
of drugs because each tissue has different characteristics: porosity, degradation,
structure, mechanical properties, etc. There is a wide area of techniques used for
the creation of biomaterials, therefore it is necessary to pay attention to the
characteristics of the biomaterial and understand the interaction that you want it to
acquire, in order to select the appropriate technique. In the field of nanomedicine, the
methods more common used for the development of biomaterials that combine HA
with starch are electrospinning, sol-gel, reaction-diffusion systems, solvent casting
(Beh et al. 2021a), thermally induced phase separation (Beh et al. 2021b), 3D
printing (Koski and Bose 2019), among others (Hosseinzadeh and Ramin 2018).
15.5.1 Electrospinning
Electrospinning has proven to be an effective technique in the production of supports
as the diameter of their fibers can be controlled, as well as their spatial orientation. It
is generally defined as the process by which fibers are made using an electric field
acting on a polymeric solution. Electrospinning begins with a drop of polymer at the
tip of a needle, which is stimulated by an electric field until it forms a surface tension
in the droplet that begins to give way, resulting in the deformation of the droplet until
it acquires a conical shape called the Taylor cone. This stage is critical since the final
morphology of the fibers depends on the correct formation of this cone. Once the
cone is formed, the surface tension exerted by the force of the electric field on the
polymer causes a deform ation on the surface of the polymer, generating fibers.
These fibers do not follow a straight path but undergo a series of electrodynamic
instabilities, resulting in a trajectory in concentric circles until they reach the
collector.
The fibers obtained through the Taylor cone are captured on different types of
collectors, depending on the spatial arrangement of the nanofibers in the support.
382 C. Chapa
Fixed collectors are used to obtain random or undirected nanofibers, while rotating
collectors are used for the generation of directed nanofibers. The matrix of the
support created by electrospun nanofibers not only provides a defined area but also
offers a spatial arrangement that is extremely important. It has been discovered that
supports with directed nanofibers are more similar to a natural 3D extracellular
matrix (ECM) than supports with undirected nanofibers, there
development and proli
feration of cells in these materials. This is a crucial character-
by enhancing the
istic for the development of a support. However, biocompatible polymeric mat erials
with both natural and synthetic materials are being investigated for applications in
tissue engineering, drug delivery and other biomedical applications (VillarrealGómez et al.
et al.
2024).
2016; K
half and Madihall y 2017;
Nave
enkum
ar
et al.
2023; Tören
Electrospinning can be utilized to create composite fibers that combine the
biocompatibility and bioactivity of hydroxyapatite with the biodegradable and
renewable properties of starch. The incorporation of hydroxyapatite into electrospun
starch fibers can enhance the mechanical properties and biological functionality of
the resulting biomaterial, making it suitable for applications in bone tissue engineering. Characteristically, this electrospinning technique allows the creation of fibers,
although it is known that the ability to control the diameter and orientation of the
fiber requires the design of experiments to test different variables ranging from the
voltage, the gauge of the syringe, to the viscosity of the polymer solution. But
once controlled, materials are obtained that even closely mimic the structure and
function of natural tissues, particularly in terms of cell adhesion, proliferation and
differentiation.
15.5.2 Sol-Gel
If we could address a method that would be versatile and effective for creating
hydroxyapatite and starch-based biomaterials with potential applications in tissue
engineering and regenerative medicine, we would be talking about the sol gel. The
method classically occurs in the following stages: hydrolysis of precursor (sol
formation), i.e. the hydrolysis of metal alkoxides to produce hydroxyl groups in
the presence of stoichiometric amounts of water and acid or basic catalyst, then
comes the polycondensation (gelation), here occurs the polycondensation of the
resulting hydroxyl groups and residual alkoxy groups to form three-dimensional
networks, then aging, drying and finally, the calcination which is performed at
increased temperatures varying within the range of 400–800 °C. During the calcination stage the dry gel structure is dehydrated. Volatile organics are also removed in
this stage. Although some authors claim to obtain polymer gels using the sol-gel
method, sometimes they do not comply with the classically involved stages, especially the calcination, therefore these methods could not be called sol-gel.
However,
but researchers have adapted it to obtain calci um phosphates as well, including
hydroxyapatite. Thus, it is said that hydroxyapatite can be prepared using the sol-gel
the method is traditionally associated with obtaining ceramic oxides,
15 Hydroxyapatite-Starch-Based Sustainable Biomaterials 383
technique and that this method is able to improve the chemical homogeneity of the
resulting hydroxyapatite, especially when it is used as a coating. The method is
simple and more accessible than the plasma spray method, currently used for
biomedical applications. Among its advantages, it has the ability to precisely adjust
the properties of the material but with an experimental design that allows control of
the variables, so we could be facing the development of new gener
ation biomaterials.
Undoubtedly, the sol-gel method is a widely used process, especially to produce
ceramics that
are then used as coatings or catalyst supports that provide stability and
regulated physicochemical properties. It could be said that the method was developed as an alternative for the preparation of glass and ceramics at low temperatures.
The final properties of the material obtained by this method depend on conditions
ring t
such as temperature and pressure du
yield
proces
an aerogel,
offers several advantages for the synthesis of hydroxyapatite-starch-based
s
while
ambi
conditions typi
ent
he drying process. Critical conditions can
produce a xerogel.
cally
The
sol-gel
biomaterials:
(a) Homogeneity: Ensures uniform distribution of hydroxyapatite within the starch
matrix.
(b) Control of Composition: Allows precise control over the ratio of hydroxyapa-
tite to starch.
(c) Low-Temperature Process: Suitable for incorporating temperature-sensitive
biological molecules.
(d) Reduction of Impurities: The use of pure precursors minimizes contamination.
(e) Encapsulation Capability: Enables the incorporation of elements such as
enzymes or growth factors.
(f) Cost-Effective Equipment: The process does not require expensive apparatus.
(g) Optical Properties: Can be advantageous for developing optical and biological
sensors.
15.5.3 Thermally Induced Phase Separation
The thermally induced phase separation technique (TIPS) consists of reducing the
temperature of a polymeric solution to induce a phase separation, what happens is
that they are separated into two phases, one with a high concentration of polymer and
the other with a low concentration. When the solvent is separated, it is removed,
leaving a space that becomes the pores of the material. Thermally induced phase
separation can be said to have two stages: phase separation and solvent removal.
Solid-liquid
crystallization inducing phase separation of the polymer solution. It is important to
say that the morphology that will be obtained by this separation will change with the
type of solvent, the crystallization temperature, and the polymer concentrations. For
the removal of the solvent, the freeze-drying process is used. Freeze-drying is
considered a technique in which a material is frozen and then dehydrated by
sublimation without losing the shape of the material. This entire process is carried
phase separation occurs when low temperature leads to solvent
384 C. Chapa
out through the freeze-dyer machine, which has the corresponding sections to carry
out the process.
The stages of the process are:
(a) Freezing. The material is put in low temperature conditions.
(b) Vacuum. Once frozen, the material is placed in a section where it will be
emptied. This allows the solvent to evaporate without passing through the liquid
phase.
15.6 Starch-Based Drug Delivery Systems
Interest in biopolymers as agents in drug delivery has grown considerably in recent
years. We can list materials such as polylactic acid (PLA), chitosan, cellulose,
alginate and of course starch. All these biopolymers have properties that make
them ideal for biomedical applications. Focusing on starch, this glucose polymer
found in the diet of virtually all humans is, obviously, biocompatible, but also
biodegradable, which gives it the stamp of sustainability. In the laboratory, it is
used to form gelled matrices capable of encapsulating drugs (Lukova et al.
Consider another example, polylactic acid is known for its biomedical applications.
It also provides us with the ability to form nanoparticles that ca n release drugs in a
controlled manner (Tudorachi et al. 2017; Pariy et al. 2022; Taib et al. 2022; Diaz
Varela et al. 2024). Certainly, chitosan, which is a chitin derivative, is also biocompatible and biodegradable, and has been widely documented and demonstrated to
have antimicrobial properties and to improve mucosal permeability, facilitating drug
release (Alvarez-Barreto et al. 2017; Marouf et al. 2020; Kedir et al. 2022). Cellulose
and its derivatives, indeed hydroxyapatite-cellulose, is an example in drug delivery
due to its ability to form films and membranes with adequate mechanical and release
properties (Morán et al. 2013). Biopolymers also include alginate, a polysaccharide
derived from algae that forms gels in the presence of calcium ions, allowing drugs to
be encapsulated and released in a controlled manner (Huq et al.
2018; Rosch et al. 2019; Thomas et al. 2021; Abka-khajouei et al. 2022; Shaikh et al.
2022). In view of the above, there is no doubt that biopolymers give us a great
diversity of options for use in the formulation of these drug delivery systems and, in
fact, their study encompasses various active substances, routes of administration and
methods of preparation. (Kamaly et al. 2016; Barclay et al. 2019; Alvarez-Barreto
et al. 2021; Valdez et al. 2022; Gaona et al. 2023).
Emphasis
properties that facilitate topical drug delivery by promoting controlled release (Mao
et al. 2004; Rydell et al. 2005; Mundargi et al. 2008; Kim et al. 2015; Okunlola and
Ghomorai 2018; Yasar et al. 2018; de Oliveira Cardoso et al. 2020; Marto et al.
2020; Ali et al. 2021; Lemos et al. 2021; Obireddy and Lai 2021; Ren et al. 2021;
Choi et al. 2022
candidate for the development of nanoparticulate drug carriers in the area of
nanomedicine lies in its natural polymeric nature of glucose monomers. The reader
should be placed on starch-based nanomedicine systems, as they offer
b’lah et al. 2023). The properties that make starch an excellent
; A
2017; Song et al.
2023).
15 Hydroxyapatite-Starch-Based Sustainable Biomaterials 385
can find recent exhaustive reviews based on natural polymers being employed in
drug delivery systems elsewhere (Fazal et al.
2023), but without a doubt starch-based
products and their derived compounds are remarkable. For example, hydroxyethyl
starch is combined with curcumin (Acevedo-Guevara et al. 2018), with Fe
3O4
for a
magnetic carrier (Castrejón-Parga et al. 2015), and with alginate to deliver
medications such as metoprolol tartrate, tolbutamide, ibuprofen, and metformin
HCl. Sustainability, as mentioned above, is due to the fact that starch sources are
merely natural.
Previously, we have talked about hydroxyapatite without emphasizing the
most recommended form for the application we have been discussing,
nanohydroxyapatite (nHAp). It is well known that nanoparticles have distinct and
outstanding properties compared to their bulk counterparts, well, the same is true for
nHAp and it is becoming a material of great interest in drug delivery systems due to
its distinctive properties (Ghorbani et al. 2019; Gui et al. 2022; Munir et al. 2022;
sghar e
A
t al. 2023) such as high surface area, porosity and inherent biocompatibility
as a calcium phosphate that mimics the mineral composition of human bone (Pandey
et al. 2018; Santillana-Marín et al. 2018; Singh et al. 2020). Of particular note,
porosity facilitates drug loading and release by allowing a high adsorption capacity
of molecules, consequently, what is being studied are the conditions to achieve
sustained and controlled drug relea se. nHAp can successfully load and release
various therapeutic agents in a controlled manner while at the same time it can be
also functionalized with various chemical groups to enhance its potential affinity for
certain drugs without compromising biocompatibility so that it does not cause
adverse responses in the body. In addition, several studies have demonstrated their
capability to enhance the antibacterial and antioxidant properties of some
compounds when nHAp is the carrier, further underscoring their multifunctionality
in biomedical applications (Ragab et al. 2014; Pandey et al. 2018; Fatimah et al.
2021; González-Torres et al. 2021; Asghar et al. 2023). For example, zinc-doped
hydroxyapatite nanoparticles loaded with ciprofloxacin have shown increased drug
loading and a tunable controlled release profile significantly improving antibacterial
and antioxidant activities (Devanand Venkatasubbu et al. 2011).
Without neglec
ting the extensively reported properties such as efficacy and
biodistribution, the property of composite materials for drug delivery that should
be gaining more relevance is the sustainability of the manufacturing processes.
Researchers currently developing such nanomedicine systems should take a growing
interest in embracing green methods for the synthesis of these materials by looking
to minimize the use of toxic solvents, reduce energy consumption and employ
renewable raw materials. Fortunately, the green synthesis of nHAp, for example,
can be carried out using plant extracts (Averous and Halley
2014;
Anaya-Barajas
et al. 2019; Sriprapha et al. 2024). Similarly, modification of biopolymers such as
starch by environmentally friendly techniques can result in materials with properties
suitable for selective, controlled, prolonged or targeted drug delivery (Morán et al.
2013; Alvarez-Barreto et al. 2021). This book is about sustainable biomaterials for
drug delivery. Therefore, it should be emphasized that hydroxyapatite can be derived
from natural sources such as eggshells, animal bones and seashells, which is where