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264 Herbal Pharmacopeia
12.3 TYPES OF NANOCARRIERS AND THEIR APPLICATIONS
In recent years, the submicron- system, i.e. nanosystem, has become popular in medicine. This is
due to these systems having advantages over traditional approaches. The latter have limitations
such as off- target effect, rapid degeneration and bioavailability. As a result of these shortcomings,
new therapeutic intervention tools have been introduced, i.e. nanocarriers. In this section, we will
explore several types of nanocarriers based on their structure, properties, and functionality, and their
applications in medicine.
12.3.1 liposoMes: struCture, funCtion, and appliCations
Liposomes have become popular and often used nanocarriers for different hydrophobic and hydrophilic molecules due to their properties like high compatibility, biodegradability, ease of synthesis,
high loading efciency, and low immunogenicity.
12.3.1.1 Structure
Liposomes were discovered by Bengham in 1960 [22]. Liposomes are spherical and their size typically ranges from 50–500nm in diameter. The emulsication of lipids in aqueous media leads to the
formation of lipid bilayers [23]. Liposomes are generally composed of two molecules, i.e. phospholipids and cholesterol (although this is not always present). Phospholipids are major molecules
composing liposomes. Phospholipids are amphiphilic, meaning that they have both a hydrophobic
region (i.e. a tail) and a hydrophilic region (i.e. a head). The structure of phospholipids consists
of two fatty acid chains (with 10–24 carbon atoms in each chain) and the hydrophilic head composed of phosphoric acid and water- soluble molecules. Water can be excluded from the hydrophobic
domain by orienting the phospholipid tails, allowing the hydrophilic heads to be exposed to water.
The structure can be seen in Figure 12.4.
The lipids commonly used in the synthesis of liposomes are either natural (phosphatidylcholine)
or synthetic (dialkyl or trialkyl lipids, 1,2-dioleoyl- sn- glycero- 3-phosphocholine).
While cholesterol is not always present, it is often incorporated because of its properties like
modulating membrane permeability, changing uidity, and improving the stability of the bilayer
membrane [24].
FIGURE 12.4 Illustration of conventional liposome, a lipid bilayer vesicle with the representation of hydrophobic tails as well as the hydrophilic head groups.
Enhanced Bioavailability of Herbal Extracts using Nanocarriers 265
FIGURE 12.5 Schematic representation of bilaminar liposome. For active targeting, the liposomal surface
can be functionalized with ligands or PEGylated. Drugs can be packed into liposomes during preparation.
Polymers and membrane proteins can also be added to liposome formulations as shown in
Figure12.5 to enhance the liposome circulation half- life, enhance the biodistribution of liposomes,
and increase the effectiveness of the medicine contained [25].
12.3.1.2 Function
Most active constituents of extracts are extremely hydrophilic and have high solubility in water, but
their absorption is low because they cannot pass through the plasma membrane due to hydrophobicity of the plasma membrane and excessive molecular size, resulting in poor bioavailability and a
loss of efcacy. To overcome this hurdle, it has been recommended that herbal medicines should be
combined with nanotechnology. Liposomes can be used as nanocarriers for hydrophilic substances.
Drugs can be loaded into the engineered liposome so that an aqueous environment encapsulates
the hydrophilic substances and adsorbed hydrophobic molecules are introduced into the membrane.
In this way, both types of substances can be loaded into the liposome [26]. Methods to achieve drug
loading into the liposome are the PH gradient technique, utilizing organic solvents, and the solvent
exchange mechanism.
Liposomes are rst engineered by adding different molecules (targeting molecules, functionalized imaging agents) onto the exposed surface of the lipid bilayer. Due to this manipulation, liposomes can target specic tissues both actively and passively.
12.3.1.3 Applications
High systemic absorption of medicines leads to off- target effects on tissue other than the intended
target tissue, which can cause unwanted side effects. Using liposome- encapsulated medicines and
their controlled release rate reduces the adverse effects and incompatibility resulting from high
systemic absorption [27].
1. Since liposomes have high substantive rates of interaction with biological membranes, this
makes them capable of easily fusing with target cell membranes, releasing the encapsulated drug directly inside the cell [27].
2. Liposomes also enhance the stability of the herbal extract by acting as a protective barrier
against light, enzymes, and heat. Liposomes improve the stability of herbal extract during
storage and delivery.
3. For the improvement of bioavailability and to lessen the adverse reaction of a medication,
liposomes are designed so they can discharge the encapsulated drug in a regulated way [28].
266 Herbal Pharmacopeia
4. Liposomes can also be helpful in delivering drugs across the blood–brain barrier and the
blood–cochlear barrier [29].
5. Liposomes are used to lower the clearance of medication and extend its half- life.
12.3.2 polyMeriC nanopartiCles: design and delivery MeChanisMs
Polymeric nanoparticles are typically ranging from 10 to 100nm in size. These polymeric nanosystems are formed by the polymerization reaction of many monomer units and under specic circumstances they can self- assemble and organize into ananometric sizes [30].
12.3.2.1 Design
This section of the chapter focuses on design considerations for polymeric nanocarriers.
12.3.2.1.1 Polymeric Material
In designing a polymeric nanocarrier, the right choice of polymer is important as this determines the
properties of the nanocarrier. Polymer carriers vary in their chemical structures and functions. The
types of polymers that can be used in nanocarrier design are described in Figure 12.6.
12.3.2.1.2 Drug Encapsulation Methods
A suitable transport device should have desirable characteristics i.e. small particle size, bioavailability, high drug- loading rate, and efcient drug encapsulation and entrapment. There are two ways to
encapsulate drugs: (1) the incorporation of the drug during the nanocarrier formulation; and (2) the
uptake of the drug after the formulation. Loading of drugs into the nanocarrier is achieved through
different methods. Among the most common are those discussed below:
FIGURE 12.6 Types of polymeric nanocarriers based on their origin.
Enhanced Bioavailability of Herbal Extracts using Nanocarriers 267
12.3.2.1.2.1 Solvent Evaporation The solvent evaporation technique involves both the polymer and the drug dissolving in an organic volatile solvent. The solvent is evaporated, leaving the encapsulated drug in the self- assembled nanocarrier [31].
12.3.2.1.2.2 Nano-Precipitation In the nano- precipitation technique, the polymer can be dis-
solved in a water- soluble solvent and then it is quickly added to water with a strong shear force,
leading to rapid precipitation of the polymer as a drug- encapsulated nanoparticle [32].
12.3.2.1.2.3 Emulsion-Based Techniques A stabilizing agent is used to emulsify an oil phase
containing the drug and polymer in an aqueous phase. And the nanoparticles dispersed in the aqueous phase are left with the encapsulated drug after the organic solvent evaporates [31].
12.3.2.2 The Delivery Mechanism of the Drug
12.3.2.2.1 Route of Delivery
There are various routes for the administration of the nanocarriers inside the body, each having its
advantages and limitations. The delivery route can be oral, nasal, pulmonary, transdermal, or subcutaneous. For polymeric nanoparticles, intravenous injection is the main route of administration [1, 33].
12.3.2.2.2 Targeting Strategies
The site of administration of drugs is often far from pathological or targeted sites. So, the nanoparticle has to reach pathological sites and release the drug. Thus, there has been a signicant study
related to targeted drug delivery. Among the important targeting strategies are:
12.3.2.2.2.1 Passive Targeting Due to rapid angiogenesis in tumors, fenestrated blood vessels are formed which make tumors more permeable than normal tissues to nanoparticles. Due to delayed lymphatic drainage, passive targeted nanoparticles penetrate the fenestrated structure of blood vessels which leads to signicant accumulations of the drug. This process is therefore called an enhanced permeation and retention effect [34].
12.3.2.2.2.2 Active Targeting Active targeting refers to the interactions between receptors and ligands. Different cell lines express different types of cell surface receptors. As a result, conjugating nanoparticles with molecules that bind to the receptors can enhance the adherence or absorption of nanoparticles into target cells. Several molecules can be utilized for this purpose, such as antibodies, antibody fragments, DNA/RNA aptamers, peptides and so on [34, 35].
12.3.2.2.2.3 Stimuli- Responsive Targeting Due to disease or inammation, the microenvironment of tissues undergoes different chemical or biological changes. The pH, oxygen concentration, temperature, and enzyme levels are all typical indicators of an abnormal state. Sensitive nanocarriers can be developed that can sense stimuli and release the drug upon stimulation. The composition or structural conformation of nanocarriers can be inuenced by chemical, biochemical, or physical stimuli, resulting in the release of drugs into a targeted environment.
12.3.2.2.3 Drug Release
Different factors are seen to inuence the drug release from the nanocarrier, i.e. drug composition
(polymer’s type etc.), chemical and physical interaction among various components of the nanocarrier and drug, composition ratio, and manufacturing methods. There are four categories that a
drug release mechanism falls into: (i) Diffusion- controlled release; (ii) Solvent control release; (iii)
Chemical interaction- based release; and (iv) Stimulated release.
268 Herbal Pharmacopeia
12.3.2.2.3.1 Diffusion- Controlled Release Due to the change in concentration gradient, the drug is diffused across the membrane. Thus, in the systems mentioned below, the dissolved or dispersed drug is diffused across the membrane and reaches the target site [36]. The two kinds of nanosystems that use diffusion- controlled release are
• Reservoir systems: The drug is encapsulated inside a central core of nanocarrier.
• Matrix systems: In this polymer matrix the drug is dispersed [37].
12.3.2.2.3.2 Solvent- Controlled Release There are two approaches involved in solvent control release, i.e., osmotic- controlled release and swelling- controlled release [38].
a. Osmotic- controlled release: This is based on the osmosis principle in which the drug
and environment are separated by a membrane that is semipermeable. This allows water
to move inside, but restricts the movement of drug molecules. When a nanoparticle is
internalized by the cell exposed to the environment where a high concentration of external
solvent is present, water starts moving inside the nanoparticle. This inux of solvent leads
to high pressure inside the nanoparticle and the release of the drug through a semipermeable membrane [36].
b. Swelling- controlled release: In the case of high solvent concentration polymers, they
absorb water and swell. As a result of this swelling, a large space is created inside the
matrix allowing for the release of the drug [38].
12.3.2.2.3.3 Chemical Interaction- Based Release In this method, biodegradable polymers are used. These can be degraded and release the encapsulated drug. The degradation process can be simultaneous or enzymatic, depending on the type of polymer used.
If polymers like polylactic acid (PLA), polycaprolactone (PCL), or polylactic- co- glycolic acid
(PLGA) are used for matrix preparation then the matrix will degrade simultaneously without the
need for enzymatic degradation. However, if polymers such as polysaccharides, polyamides, and
polyesters are used then they release the drug through enzymatic degradation [36].
12.3.2.2.3.4 Temperature- Controlled Release Heat- responsive polymers are used in nanocarrier synthesis. These polymers release the drug upon the slightest change in temperature since in response to heat these polymers can change their chemical and physical properties [39]. These thermo- responsive nanocarriers have gained popularity in recent years, as studies show that inammatory diseases and tumors show abnormal temperatures due to high metabolic activity [40].
Besides temperature changes brought on by disease tissue, the temperature can also be changed
by extrinsic factors in particular tissues. When subjected to temperature change, the polymer undergoes go a structural change which results in a shift in hydrophobicity or solubility Below a certain
temperature, they are hydrophilic; above that, they are hydrophobic [41, 42].
12.3.3 nanoeMulsions: forMulation and stability
As the name suggests, nanoemulsions are two insoluble liquids (either oil in water droplets or water
in oil), stabilized by an amphiphilic surfactant. There are different techniques, such as high- pressure
homogenization and ultrasonication, for rupturing large microscale droplets into nanoscale droplets
[43]. Typically, a mean droplet diameter attained is <500 nm [44]. Nanoemulsions come under a
broad class of multiphase colloidal dispersion. Nanoemulsion is sometimes also called submicron
emulsion or mini emulsion, but it is entirely different from microemulsion in terms of structure and
thermodynamic stability [45].
Enhanced Bioavailability of Herbal Extracts using Nanocarriers 269
12.3.3.1 Formulation
Major components of nanoemulsion include: (1) lipids/oils; (2) surfactants and co- surfactants; and
(3) preservatives, chemo- protectants, and antioxidants.
i. Oil/lipid: In the case of oil/water emulsion, the percentage of oil/lipid droplets it contains
is 5–20% generally, but sometimes it can increase up to 70%. Long- chain triglyceride,
medium- chain triglyceride, and short- chain triglycerides like safower oil and soyabean
oil are used to formulate nanoemulsions. They can be used alone or can be combined to
formulate nanoemulsions [46, 47]. A carrier in the nanoemulsion D- α-Tocopherol (vitamin
E) family can be used [48].
ii. Surfactants and co- surfactants: Surfactants have polar heads and non- polar tails, and
they should be highly soluble in one liquid. Because of the difference in attractive interaction between molecules of two liquids, in all situations where a liquid phase contacts
another liquid phase, there is an interfacial tension σ [43]. Nanoemulsions are stabilized
by surfactants since they have ability to lessen the interfacial tension and prevent droplets
from aggregating. Lecithin is a common surfactant used in nanoemulsion [49].
iii. Preservatives, chemo- protectants, and antioxidants: We use preservatives to inhibit the
growth of microorganisms. Preservatives should have low toxicity, chemical and physical
compatibility, affordable cost, acceptable odor, color and taste, stability to heat and storage,
and a broad anti- microbial spectrum. Quaternary ammonium compounds and phenolics
can be used as broad- spectrum preservatives [50].
12.3.3.1.1 The Generation of Nanoemulsion
The stability of nanoemulsion depends on many factors that need to be controlled. These factors
include choosing the appropriate composition, effective shear application to rupture droplets effectively, and sequence of component addition. There are three types of tailoring techniques for forming nanoemulsions: high- energy emulsication, low- energy emulsication, and a combination of
low and high energy.
12.3.3.1.1.1 Emulsication by High- Energy Method In this method, mechanical devices are
used to generate strong disruptive forces for size reduction. Mechanical apparatus such as ultrasonicators, high- pressure homogenizers, and microuidizers. For example, ultrasonication uses highfrequency sound waves (20khz and up). Nanoemulsions can be formed in situ or preformed
emulsions can be reduced in size using ultrasonication. Cavitation bubbles form when ultrasonic
waves are dipped in samples; these bubbles continue to grow until they reach their limit and implode.
This implosion produces a shock wave. As a result, a jet stream of liquid is created in the surrounding area, decreasing the size of dispersed droplets by pressurizing them [51]. The simple process
involves the adding oil phase to the aqueous phase with continuous shaking to produce a coarse
emulsion. Afterwards, the prepared emulsion is exposed to ultrasonication at different amplitudes
until the desired characteristics are obtained [50].
12.3.3.1.1.2 Emulsication by Low- Energy Method
This process involves spontaneous emulsication [52] and the phase inversion method. Spontaneous
emulsication is particularly used for the synthesis of polymeric nanoparticles. The overall process
involves the preparation of two phases: an aqueous phase, which contains hydrophilic surfactant;
and a second phase containing , oil . The forming of a nanoscale emulsion requires the continuous
stirring of the aqueous phase and the dropwise addition of oil or the organic phase. Oil nanoemulsions can form spontaneously because the increase in entropy (disorder) from spreading the oil into
tiny droplets outweighs the energy needed to break them up. The overall process can be initiated
by itself or might require a little external energy (which can be supplied by a magnetic stirrer) [50].
270 Herbal Pharmacopeia
12.3.3.2 Stability
12.3.3.2.1 Physical Stability
Nanoemulsions have a small size due to which they have advantages such as better physical stability against droplet aggregation, high optical clarity, and enhanced bioavailability of drugs. A lowviscosity oil emulsion produces signicantly smaller droplets than a high- viscosity oil emulsion. In the
same study, it is found that increased concentration of alcohol up to 10 wt.% leads to decreased droplet
size. However, with a further increase in alcohol concentration, the droplet size begins to increase.
This shows that at optimum concentrations, alcohol enhanced solvent performance [53]. In addition,
natural stabilizers such as eugenol are also useful in obtaining more stable nanoemulsions [54].
12.3.3.2.2 Chemical Stability
To avoid chemical degradation, it is advisable to design nanoemulsions to avoid light- catalyzed
reactions that may occur due to the transparency of nanoemulsion and surface- catalyzed reactions,
i.e. lipid oxidation may occur because of high interfacial areas [55]. Also, bioactive lipids such as
carotenoids, conjugated linoleic acid and so on, which are incorporated into nanoemulsions are
unstable [56, 57]. To tackle these problems with solutions a number of steps can be taken, such as
maintaining low storage temperature, incorporating appropriate antioxidants, controlling droplet
interfacial properties, and chelating transition metal catalysts [55].
12.3.4 MiCelles: enhanCing solubility and bioavailability
Micelles are colloidal structures with a diameter of between 5 and 200nm which are amphiphilic.
Critical micellar temperature and critical micelle concentration (CMC) are the specic temperature
and concentration at which molecules aggregate to form a micelle. By forming the hydrogen bonds
in water and removing the micelle's hydrophobic fragments from the aqueous environment, amphiphilic molecules aggregate into micelles, reducing the free energy of the system [58]. Micelles
can be polymeric micelles (poly ethylene oxide- poly(propylene oxide) [59] and triblock copolymer
micelles (poly (ethylene oxide)-poly (aspartic acid) block copolymer (PEO/PASP (ADR)) and so on
[60]. Figure 12.7 shows polymeric micelles as hydrophobic drug carrier.
FIGURE 12.7 Polymeric micelles as hydrophobic drug delivery nanocarriers. Polymeric micelle with a
hydrophobic core and hydrophilic shell, allowing for the encapsulation and delivery of hydrophobic drugs.
Enhanced Bioavailability of Herbal Extracts using Nanocarriers 271
12.3.4.1 Enhancing Solubility and Bioavailability
The factors affecting the amount and speed of absorption of a drug include its solubility and gastrointestinal permeability [61]. The aqueous solubility of therapeutics plays an important role in
absorption after drug administration [62]. The biopharmaceutics’ classication indicates that Class
II and IV drugs (APIs) are poorly soluble, bioavailable, and dissolvable.
In this section we will discuss micelles and polymeric micelles [63]. Nanocarriers can enhance
the solubility and bioavailability of hydrophobic drugs. Of these, the most promising nanocarrier is
the micelles system which can improve the drug’s solubility due to its core–shell structure and can
also control drug release. Two of the prominent ways to increase the solubility of drug- using micelles
systems are the following:
12.3.4.1.1 Micellar Solubilization
This approach involves the incorporation of components into or onto the micelles. One of the
most important properties of the micelle is that it can enhance the water solubility of compounds.
Plotting the solubility of a substance with low water solubility as a function of surfactant concentration typically leads to the conclusion that drug solubility is signicantly lower until the surfactant concentration approaches the CMC. Solubility increases linearly with surfactant concentration
after it reaches concentrations higher than the CMC, suggesting that solubilization is important for
micellization [63].
12.3.4.1.2 Polymeric Micellar Nanocarriers
Another approach to improve the solubility of weekly soluble drugs is through their incorporation into surface active agents. Amphiphilic copolymers with hydrophobic and hydrophilic building
blocks dissolve in an aqueous solution to form micelles [64, 65]. Hydrophobic domains constitute
the core of the micelles while the hydrophilic copolymer tails constitute the outer shell. Lipophilic
drugs are entrapped in the core. The solubility of lipophilic medicine can be enhanced by incorporating micellar carriers within the micellar core [66]. Amphiphilic block copolymers offer a
promising alternative to traditional delivery systems for hydrophobic drug delivery with increased
bioavailability.
12.4 NANOCARRIERS AND SOLUBILITY ENHANCEMENT
12.4.1 teChniques for iMproving the solubility of hydrophobiC CoMpounds
The use of nanocarriers has emerged as the most promising method for improving the solubility of
hydrophobic drugs and increasing bioavailability. Some nanocarriers are employed often to enhance
hydrophobic drug solubility:
12.4.1.1 Lipid Dispersion Techniques
The lipid dispersion method is the synthesis of nanoparticles using lipid excipients. Dispersions of
lipids are more suitable for the drug to be encapsulated as this process has features such as being low
water- soluble, and having high lipid solubility, and a low melting point.
1. Solid lipid nanoparticles
Solid lipid nanoparticles (SLNs) developed from oil/water emulsions [67]. SLNs solidify
at room temperature and body temperature. SLNs offer several benets as drug carriers,
such as facilitating the absorption of drugs, high drug loading and regulated drug release.
Because of these features, in order to enhance the oral bioavailability of readily soluble
drugs, solid lipid nanoparticles are more suitable for formulation. SLNs can be produced
by the high- pressure homogenization technique [68]. SLNs are now considered a possible
way to increase the bioavailability of hydrophobic drugs.
272 Herbal Pharmacopeia
2. Nanostructured lipid carriers
Solid lipids have a lower ability to dissolve poorly soluble drugs when compared with
liquid lipids. To overcome this limitation of SLNs, nanostructured lipid carriers (NLCs)
have been developed. NLCs are created simply by adding liquid lipids to the core of the
SLNs. Due to their exceptional solubilizing and dispersion abilities, NLCs have emerged
as a potential nanocarrier for poorly soluble drugs [69, 70].
3. Nanoemulsions
Pharmaceutical nanoemulsions are made up of the water phase, the emulsier co- emulsier
phase, and the oil phase. Liquid lipid oil is employe to formulate nanoemulsions, which
offer a high capacity for readily soluble drugs. Because of their particle size, which is less
than 100nm, they have a large surface area for high drug dispersibility and absorption [71].
4. Liposomes
Of all the liposome preparation methods, the lm hydration method is the most developed
and widely used. In this procedure, the drug is completely dispersed in the lipid mixture.
5. Micellar solubilization
By lowering the surface tension in aqueous solution, surfactants efciently increase the
solubility of hydrophobic drugs. Drug suspensions can also be stabilized by surfactants.
Micelle formation happens when the concentration of surfactants exceeds their critical
micelle concentration, which is typically between 0.05 and 0.10%, entrapping the hydrophobic drug inside the micelle in a process known as micellization. Micellization enhances
the solubility of drugs that are readily soluble in aqueous media. Micellar solubilization is
the preferred substitute for dissolving poorly soluble medications [72].
6. Polymeric composite (solid dispersions)
Polymeric composite is not a lipid dispersion technique. Solid dispersions involve the
incorporation of not readily soluble drugs in a hydrophilic polymeric matrix, which may
improve the solubility of drugs and the rate of dissolution in aqueous media. After reaching the target site, the hydrophilic polymer dissolves, releasing the ne particles of the
drug [73]. Solid dispersion has proved a familiar method for improving the aqueous solubility and dissolution rate of BSC II drugs (poorly soluble but highly permeable, limiting their dissolution and absorption). Hydrophilic polymeric matrices such as poloxamer
407, carboxymethylcellulose, poloxamer 188, polyvinylpyrrolidone etc. can be used for
solid dispersion preparation. A variety of techniques, including melting, kneading, solventevaporation, and lyophilization, can be used to create solid dispersions.
The solvent- evaporated dispersion is one of the most effective techniques to enhance the aqueous
solubility and dissolution rate of BSC class II drugs. A clear and transparent solution is produced by
completely dissolving the drug and polymeric matrix in a solvent system. The dried product is then
obtained by evaporating this clear solution. Drug molecules are dispersed evenly or trapped within
the polymeric compound in a solvent- evaporated solid dispersion [74].
a. Case Studies of Solubility Enhancement Using Nanocarriers
i. Case study 1: Enhancement of Silymarin solubility using PVP- PEG polymeric composite
Silybum marianum belongs to the Asteraceae family and is used to treat hepatic
diseases. Silymarin is an extract derived from the fruits and seeds of Silybum mari-
anum. There are four isomeric avonoids in silymarin: silybinin, isosilybinin, silydianin, and silychristin. In the pharmaceutical industry, silybinin is of the utmost
importance. Silymarin is well known for itsanticarcinogenic, hepatoprotective, and
anti- inammatory properties. It also acts as a strong antioxidant, restores damaged
hepatocytes, detoxies harmful substances, and stabilizes cell membranes. It is considered an effective decongestant for the liver and kidneys.
Enhanced Bioavailability of Herbal Extracts using Nanocarriers 273
Challenge: Oral drug administration is the most practical and safe way. Solubility of
the drug in gastrointestinal (GIT) uid is crucial in the absorption of orally administered drugs. Silymarin belongs to the BSC II class and such compounds are only poorly
soluble in aqueous solutions. The low solubility of silymarin hinders its absorption and
reduces its effectiveness as a therapeutic agent.
Proposed solution: Researchers developed a novel approach in which they used a
polymeric composite made of polyvinylpyrrolidone (PVP) and polyethylene glycol
(PEG) to increase the solubility of silymarin [74].
Method
• Silymarin was incorporated into the PVP- PEG composite via the solvent evapora-
tion method.
• PVP K- 30 and PEG 6000 ratios were experimented with to maximize the compos-
ite’s capacity to improve silymarin’s solubility.
Results: The study shows that the polymeric composite increases the solubility of silymarin by 1150 folds. The drug's maximum aqueous solubility was shown by the ratio
0.25/1.5/1.5 (w/w/w) for PVP K- 30, and PEG 6000.
The study suggests that solubility increases due to the increased surface area,
increased interaction between PVP- PEG with water and the formation of a silymarin
amorphous state facilitated by composite [74].
ii. Case Study ii: Improving Curcumin Solubility and Delivery using Solid Lipid Nanoparticles
Curcuma longa belongs to the Zingiberaceae family, and its active compound is curcumin, which has antibacterial, antidiabetic, anti- inammatory, antioxidant and antitumor properties. Several studies show that curcumin is effective in the treatment of
GIT disorders, liver disorders, and inammatory conditions. It also shows effectiveness
in cancer management by reducing protein levels like Cyclin D1 and CDK4, which are
involved in cell proliferation.
Challenges: Curcumin has multiple uses, but due to its low bioavailability, rapid
metabolism, almost complete insolubility in water (about 11 ng/ml), and physiological
instability, it has not been effectively used as a therapeutic drug. All these factors lead
to its poor absorption and reduced effectiveness as a therapeutic agent.
Proposed solution: Scientists proposed SLNs as drug delivery vehicles to overcome
the above- mentioned problems. SLNs increase the drug’s solubility, provide protection
against degradation, and make the drugs more bioavailable.
Method: The high- pressure hot homogenization technique was used to prepare the
curcumin- loaded SLNs technique. Curcumin was encapsulated within a lipid core and
the lipid used was CompritolR888 ATO and GMS (4:1). To attain a 1.5% w/v curcumin
concentration in the SLN dispersion, various formulations were prepared using a variety of types and concentrations of lipids and phospholipon 90G.
Results: In this study, researchers developed a high- drug loading CLEN dispersion that
contains 15 mg of curcumin per ml, along with a high drug loading of 15%. According
to reports, there is the largest increase in solubility of curcumin in aqueous solution
(1.4×106 times higher than 11ng/ml in water for free curcumin) combined with high
drug loading so far [75].
12.5 STABILITY OF HERBAL EXTRACTS IN NANOCARRIER SYSTEMS
The primary issue of using herbal extracts is their sensitivity to ultraviolet light, oxygen, enzymes,
and chemicals. They also undergo a degradation process in the GI tract before entering the circulation. These drawbacks restrict the number of applications for these herbal extracts. Consequently, an