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Trends in Food Science & Technology 46 (2015) 60e67

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Trends in Food Science & Technology


journal homepage: http://www.journals.elsevier.com/trends-in-food-scienceand-technology

Review

Ultrasound applications for the extraction, identication and delivery


of food proteins and bioactive peptides
b

Shekhar U. Kadam a, Brijesh K. Tiwari b, *, Carlos Alvarez
, Colm P. O'Donnell a
a
b

School of Biosystems and Food Engineering, University College Dublin, Beleld, Dublin 4, Ireland
Department of Food Biosciences, Teagasc Food Research Centre, Dublin 15, Ireland

a r t i c l e i n f o

a b s t r a c t

Article history:
Received 3 January 2015
Received in revised form
23 June 2015
Accepted 14 July 2015
Available online 17 July 2015

Bioactive peptides in foods can be obtained from plants, animal or marine sources. Bioactive peptides
possess diverse biological activities such as opiate, antithrombotic, anti-hypertensive, immunomodulating, antilipemic, osteoprotective, antioxidative, antimicrobial, ileum contracting, anticariogenic and
growth promoting properties. In general, peptide based drugs are physically and chemically unstable,
have short in vivo half-lives and have low oral bioavailability. Ultrasound which is a novel, robust, green
and rapid technology suitable for scale up, can enhance the efciency of protein digestion, extraction,
production and drug delivery of bioactive peptides. Ultrasound principally acts by generating bubble
cavitation in the biological matrix. It has been extensively reported for extraction of proteins and peptides from natural products facilitating higher yields and rates of extraction. Ultrasound assisted
encapsulation of peptide based drugs with biodegradable polymers can improve stability and bioavailability. Moreover, in sonophoresis applications, low-frequency ultrasound can be used to transport high
molecular weight peptide drugs. This review paper summarizes key bioactive peptides, sources, structure, function and application of ultrasound for production and drug delivery of peptides.
2015 Elsevier Ltd. All rights reserved.

Keywords:
Ultrasound
Bioactive peptide
Digestion
Extraction
Drug delivery
Microencapsulation
ACE inhibitory peptide

1. Introduction
Recent developments in functional food research have
generated renewed interest in bioactive compounds including
bioactive peptides. The word peptide comes from the Greek
term p3ptidia translated as small digestibles or digested
(Shahidi & Zhong, 2008). Biological activity of peptides were rst
reported by Mellander in 1950. In the last two decades there has
been a strong interest in bioactive peptide identication and
characterization. Researchers continue to investigate new sources, extraction methods and evaluate health benets of bioactive
peptides. Bioactive peptides are specic protein fragments that
can alter body functions or conditions and may ultimately inuence health positively (Korhonen & Pihlanto, 2006). Such
peptides are inactive within the sequence of the parent protein
and can be released by several hydrolysis techniques. Bioactive
peptides have potential to help reduce the worldwide epidemic
of chronic diseases affecting 58 million people annually (Sun,

* Corresponding author.
E-mail address: Brijesh.tiwari@teagasc.ie (B.K. Tiwari).
http://dx.doi.org/10.1016/j.tifs.2015.07.012
0924-2244/ 2015 Elsevier Ltd. All rights reserved.

2013). Currently the market for functional proteins and peptides is valued at $75 billion/year (Sun, 2013). Peptide based
drugs sales are growing at a rapid pace with annual sales of $20
billion corresponding to 2% of the global drug market (Sun,
2013). Bioactive peptides from food proteins offer major potential for incorporation into functional foods and nutraceuticals.
Major drivers for bioactive peptides drugs include their role as
hormones, neurotransmitters and neuromodulaters, and low
toxicity or non-toxicity of metabolic cleavage products. Challenges associated with the introduction of new peptide products
include proteolytic degradation, fast clearance in the body, low
solubility in water, immunogenicity (Bellmann-Sickert & BeckSickinger, 2010) and regulatory hurdles. Inactive or latent form
of bioactive peptides in parent protein can be activated by proteolysis (Ryan, Ross, Bolton, Fitzgerald, & Stanton, 2011). Bioactive peptides may be produced by several methods: the most
commonly employed are based on enzymatic hydrolysis by
digestive enzymes derived from micro-organisms and fermentation of food proteins (Kim & Wijesekara, 2013). However other
methods based on chemical hydrolysis or sub-critical water hydrolysis have also been widely researched in recent decades
(Rogalinski, Herrmann, & Brunner, 2005).

S.U. Kadam et al. / Trends in Food Science & Technology 46 (2015) 60e67

Sample preparation is one of the major limiting steps for rapid


protein and peptide identication. Traditional methods of sample
treatment are laborious, time consuming and involve use of
pez-Ferrer et al., 2006). To reduce the time of
chemical solvents (Lo
sample preparation for protein and peptide identication, many
measures have been investigated either separately or combined
which include use of higher temperature during the digestion step,
use of columns containing immobilized trypsin and addition of
organic solvents. Use of novel techniques including high intensity
ultrasound, microwave processing (Lopez-Ferrer, Capelo, &
, Pare
s,
Vazquez, 2005) and high hydrostatic pressure (Toldra
Saguer, & Carretero, 2011) have also been explored.
Ultrasound waves are sound waves that exceed the hearing limit
of frequency of the human ear i.e. above 20 kHz. Ultrasound principally acts by generating bubble cavitation in the biological matrix.
The various principal mechanisms of generation of bubble cavitation by ultrasound are shown in Fig. 1. Recent advances and developments have led to the introduction of more efcient and
versatile ultrasound instrumentation which has expanded the potential applications of ultrasound in the food and biopharmaceutical industries (Awad, Moharram, Shaltout, Asker, & Youssef, 2012).
The main applications of ultrasound in food biotechnology are
outlined in Fig. 2. Application of ultrasound results in physicochemical changes to proteins and peptides owning to/via sonochemical reaction, sonolysis of water, formation and collapse of
cavitational bubble and microstreaming (O'Donnell, Tiwari, Bourke,
& Cullen, 2010). Ultrasound is reported to be economically feasible
and, meets process requirements including scale up (Chemat, Zill e,
& Khan, 2011). The objective of this paper is to review reported
applications of ultrasound for extraction, digestion, generation,
encapsulation and controlled release of peptides and proteins.
Bioactive peptides, their types, sources and biological activities are
also outlined.
2. Bioactive peptides
2.1. Sources
Bioactive peptides in foods may be obtained from plants, animal or marine sources. Plant peptides, with molecular weight less
than 10 kDa, can essentially be divided into two categories:
bioactive peptides that are produced by selective action of peptidases on larger precursor proteins and degraded peptides that

61

result from the activity of proteolytic enzymes during protein


turnover. Bioactive peptides such as hypogin (peanut), angularin
(adzuki bean), lunasin (soybean and barley) have been shown to
have medicinal properties. Plant peptides also include glutathions
and protease inhibitors such as BowmaneBirk inhibitors and
mustard trypsin inhibitors (McGurl, Pearce, Orozco-Cardenas, &
Ryan, 1992). Interestingly, most of the therapeutic peptides
initially discovered were sourced from animal venoms and toxins
(Redwan, 2009). Recently research has focused on discovery of
new bioactive peptides from animal sources. Moreover, biofunctionalities and isolation procedures of previously discovered
bioactive peptides are well documented in the literature. Peptides
from animal sources possess biological activities such as antihypertensive, antioxidant, antimicrobial and antiproliferative activity
(Ryan et al., 2011). Sources such as milk, egg and meat have been
given special consideration due to their abundance in the human
diet and documented biological activities. Enzymatic digestion is
one of the common methods to obtain peptides from protein
hydrolysates of meat products. In addition to this, fermentation of
meat products is an alternate method to generate bioactive peptides by proteolytic enzymes during microbial fermentation
(Arihara, 2006).
The marine environment provides half of the total global
biodiversity. Marine bioresources have been investigated as a
source of novel compounds for pharmaceutical and nutraceutical
applications. Due to the competitive and aggressive nature of
habitats, marine species develop specic and potent bioactive
molecules (Aneiros & Garateix, 2004). Marine derived biologically
active peptides are reported to have a range of functionalities
including enzyme inhibition, mineral binding, immunomodulatory,
antimicrobial, antioxidant, antithrombotic, hypocholesterolemic,
and antihypertensive actions (Kim & Wijesekara, 2010). Moreover,
fish protein hydrolysates and peptides thereof have been shown to
have bioactive properties. Bioactive peptides and depsipeptides
with functional properties have also been isolated from tunicates,
sponges, soft corals, sea hares, nudibranchs, bryozoans, sea slugs,
tunicates, sponges, mollusks and other marine organisms (SuarezJimenez, Burgos-Hernandez, & Ezquerra-Brauer, 2012).
2.2. Structure and function
Peptides are formed by condensation of two or more amino
acids. Peptides are classied into ribosomal and non-ribosomal

Fig. 1. Mechanism of bubble cavitation phenomenon.

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S.U. Kadam et al. / Trends in Food Science & Technology 46 (2015) 60e67

Fig. 2. Applications of ultrasound in food biotechnology.

classes. Peptides can also be classied on the basis of their bioactivity. The applications of peptides have evolved from being a
simple source of nitrogen and energy towards applications in human health (Fig 3). Peptides possess diverse biological activities
such as opiate, antithrombotic, anti-hypertensive, immunomodulating, antilipemic, osteoprotective, antioxidative, antimicrobial,

ileum contracting, anticariogenic and growth promoting properties


ller, Scholz-Ahrens, Roos, & Schrezenmeir, 2008). In recent
(Mo
years, the production of synthetic, modied, constrained or conjugated peptides has been researched. Peptides can be employed to
create new protein-peptide scaffolds and as antimicrobial agents,
drug carriers, peptide vaccines and glycemic regulators. (Kaspar &

Fig. 3. Evolution of peptides and applications. Modied from (Sharma, Singh, & Rana, 2011).

S.U. Kadam et al. / Trends in Food Science & Technology 46 (2015) 60e67

Reichert, 2013; Kastin, 2013; Michael Henderson & Lee, 2013;


Reichen, Hansen, & Plckthun, 2013).
3. Applications of ultrasound
Application of ultrasound can be characterized according to
frequency and power, namely low frequency/high power
(<16e100 kHz and power from 10 to 1000 W cm2) and high frequency/low power (100 kHz to 10 MHz and power < 1 W cm2)
ultrasound (Soria & Villamiel, 2010). Low power ultrasound is
mainly used in medical diagnostics whereas high power ultrasound
is used to induce physical and chemical changes in biological
matrices due to mechanical, cavitational and thermal effects.
Implosion of cavitational bubbles, formation of microjets, microturbulence, high-velocity inter-particle collisions and perturbation in micro-porous particles (Shirsath, Sonawane, & Gogate,
2012) result in enhanced extraction yield and accelerated chemical reactions (Kadam, Tiwari, & O'Donnell, 2013). Formation and
collapse of cavitational bubbles generate extremely high local
temperatures (in excess of 5000 K) and high pressures (500 atm)
along with formation of free radicals (Rokhina, Lens, & Virkutyte,
2009) due to sonolysis of water (H2O / OH H,
H2O OH H / H2O2 H2). Over the past decade, ultrasound
has been increasingly investigated in peptidomics and encapsulation applications for controlled release of peptides. Ultrasound
mechanisms for selected proteins and peptides applications are
outlined in Table 1. Emerging ultrasound applications in food
biotechnology and pharmaceuticals are outlined in Fig 4.
However, high power ultrasound treatment for longer treatment times can generate high temperature and pressure conditions
which can alter the native state of food protein or peptide. Wave
attenuation with distance in dispersed phase systems is a specic
challenge with ultrasound assisted extraction (UAE) technologies,
particularly with samples containing small gas bubbles. Thus, it is
necessary to optimize the treatment conditions for specic ultrasound applications to achieve optimum results.
3.1. Protein digestion
Protein digestion is an important step in protein identification, characterization, quantification and in the generation of
bioactive peptides. Generally protein digestion is carried out
using proteolytic enzymes or acid hydrolysis performed insolution (overnight) or in-gel (24e72 h) (Capelo et al., 2009).
Both of these traditional methods require lengthy sample preparation, thus making digestion one of the major bottlenecks in
bottom-up proteomics (Switzar, Giera, & Niessen, 2013). Lengthy
digestion processes in proteomics do not guarantee reproducibility due to matrix heterogeneity of proteins (Capelo et al.,
2009). Many emerging accelerated techniques are reported in
the literature for improving digestion efciency including sub/
super-critical water hydrolysis, microwave, ultrasound, high

63

pressure, infrared, magnetic particle immobilized enzymes and


on-chip immobilized enzymes (Switzar et al., 2013). Use of ultrasound to enhance enzymatic reaction is known as ultrasonicassisted enzymatic digestion (USAED). It is a robust, rapid and
cost effective technology. The effect of ultrasound on biological
systems has been widely reported. In the early 1980's the role of
ultrasound to enhance enzyme activity of a-chymotrypsin,
catalase, malate deshydrogenase and lipase enzymes was reported. However some studies reported inactivation of enzyme
after repeated sonication (Ishimori, Karube, & Suzuki, 1981;
Kashkooli, Rooney, & Roxby, 1980; Kwiatkowska, Bennett,
Akunna, Walker, & Bremner, 2011). Inactivation of enzymes is
caused due to denaturation of proteins either by generation of
free radicals from sonolysis of water molecules or shear forces
resulting from the formation or collapse of cavitating bubbles
(O'Donnell et al., 2010). A recent study by Yu, Zeng, Zhang, Liao,
and Shi (2013) demonstrated that the effect of ultrasound is
enzyme specic. They reported that while the activity of pepsin
was enhanced, both a-amylase and papain were inhibited under
the same sonication conditions namely at a frequency of 40 kHz
and at power level of 278.8 7.4 W. It was suggested that
observed changes in activity were mainly due to variations in the
secondary and tertiary structures. Ultrasonic bubble cavitation
causes crushing, which results in large mechanical shearing
forces, which degrade protein structure and open up hydrophilic
groups. This opening up of structure increases the protein solubility and allows the protease to bind more easily with the protein substrate. This increases the efciency of hydrolysis (Yu
et al., 2012). However to date USAED has only been used for
off-line digestion systems. Lopez-Ferrer et al. (2005) employed
power ultrasound to achieve in-solution and in-gel tryptic
digestion of proteins which was measured by mass spectrometry.
They concluded that ultrasonic bubble cavitation causes not only
temperature and pressure changes but also shear forces, jets, and
shock waves which result in rapid mixing of reaction components. This decreases proteomic digestion time to 1e3 min
 pez-Ferrer et al., 2008).
without any undesirable side effects (Lo
Various extrinsic and intrinsic factors inuence the efciency of
USAED. For example, incubation temperature and digestion time
are directly proportional to the number of peptides identied from
protein except at a temperature of 55  C, due to a high ratio of
miscleavage compared to conventional techniques (Shin, Yang,
Kim, & Kim, 2011). USAED requires smaller quantities of sample
for protein digestion and further analysis compared to traditional
methods. Both ultrasound bath and probe systems are employed
for protein digestion applications, ultrasound baths require longer
treatment times compared to ultrasound probe systems due to the
lower ultrasonic energy applied. However in sonoreactor applications, lower standard deviation, cleaner mass spectra and a higher
percentage of protein sequence coverage were achieved compared
to ultrasonic probe based systems. This was attributed to the gel
degradation and more contaminant peaks in high power

Table 1
Ultrasound mechanisms for different applications.
Application

Ultrasound mechanism

References

Protein digestion

Ultrasonic bubble cavitation causes rapid changes of temperature, pressure, shear forces, jets, and shock waves
which results in mixing of reaction components instantly and proteolysis
Implosion of cavitational bubbles, formation of microjets, micro-turbulence, high-velocity inter-particle collisions
and perturbation in micro-porous particles results in enhanced extraction yield and accelerated chemical reactions
Increase in the surface hydrophobicity and loosening of protein for easy release of peptides

pez-Ferrer et al.,
(Lo
2008)
(Shirsath et al., 2012)

Isolation/Extraction of
protein
Production of ACE
inhibitory peptide
Encapsulation of
bioactive peptides
Sonophoresis

Capillary wave and bubble cavitation disintegrates liquid for atomization

(Huang, Liu, Ma, &


Zhang, 2014)
(Avvaru et al., 2006)

Ultrasonic cavitation and non-cavitational effects increase skin permeability

(Polat et al., 2011)

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S.U. Kadam et al. / Trends in Food Science & Technology 46 (2015) 60e67

Fig. 4. Application of ultrasound to proteins and peptides.

ultrasound probe applications (Rial-Otero et al., 2007). Rapid


denaturation of protein during USAED can be overcome by using
highly stable cross-linked enzyme aggregates of tissue-culturegrade trypsin which can maintain an activity of 92.6% (Wang, Mu,
Qi, Su, & He, 2013). USAED can be applied to in-gel and insolution separated proteins. Moreover, it can speed up denaturation, reduction, alkylation, and digestion steps in proteomics
(Capelo et al., 2009).
3.2. Isolation/extraction of proteins
Ultrasound is a novel technology extensively reported for
extraction of bioactive compounds from natural products. UAE has
been used to extract proteins from various sources including soybean (Moulton & Wang, 1982), wheat germ (Zhu, Sun, & Zhou,
2009), defatted rice bran (Chittapalo & Noomhorm, 2009),
brewers spent grain (TaNg et al., 2010), rapeseed (Dong et al., 2011),
sorghum (Bean, Ioerger, Park, & Singh, 2006) and perilla seed (Zhu
& Fu, 2012). Li, Yu, Ahmedna, and Goktepe (2013) studied the effect
of ultrasound and enzymatic treatment on soluble proteins and
allergenic peanut proteins. Their results showed that ultrasound
increased the solubility of peanut protein, enhanced cleavage of
peptide bonds and loosened the peanut kernel structure. According
to Dong et al. (2011) UAE was signicantly better than traditional

alkaline extraction and acidic precipitation for rapeseed protein


extraction. Kim, Kim, Kim, Park, and Lee (2012), observed that the
treatment time required to extract 20% collagen from sea bass
Lateolabrax japonicas reduced with an increase in ultrasound
amplitude. Similarly protein release from dry wine yeast was found
to improve with an increase in duty cycle (Liu, Zeng, Sun, & Han,
2013). Microstructural studies using SEM indicate that higher
amplitude increased the severity of cell structure disintegration,
thus facilitating complete rupture of defatted soy akes cell with
increased amount of fragmented cell matter (Karki et al., 2010).
3.3. Production of ACE inhibitor peptides
Angiotensin I-converting enzyme (ACE) inhibitor peptides have
been widely investigated to reduce hypertension and replace ACE
inhibitor drugs. ACE (dipeptidyl carboxpeptidase, EC 3.4.15.1),
through its action on renin-angiotensin system and kinin-kalicrein
ndez-Ledesma, del
system increases human blood pressure (Herna
Mar Contreras, & Recio, 2011). ACE inhibitor peptides can be
sourced from food sources including dairy, sh, chicken egg, wheat,
corn, soybean and garlic. (Kadam & Prabhasankar, 2010; Li, Le, Shi,
& Shrestha, 2004). Traditionally, these peptides can be produced
from parent protein hydrolysis using enzymes including pepsin,
pancreatin, trypsin, chymotrypsin, thermolysin, subtilisin or

S.U. Kadam et al. / Trends in Food Science & Technology 46 (2015) 60e67

combinations thereof (Marczak et al., 2003). ACE inhibitory peptides, can be divided into three groups, namely substrate, inhibitor
and prodrug type due to presence of ACE substrates in enzymatic
food protein digests (Iroyukifujita, Eiichiyokoyama, & Yoshikawa,
2000). An overview of ACE-inhibitory peptides is outlined in
Fig. 5. Jia et al. (2010) used ultrasound pre-treatment to enhance the
breakdown of defatted wheat germ protein to yield ACE inhibitor
peptides. On average the breakdown rate constant increased by
22.2% when treated with ultrasound at 22 kHz frequency and 40 W
for 210 min. Ultrasound treatment also elevated ACE inhibitor activity levels. Zhou et al. (2013) reported that an ultrasound probe
system can deliver better ACE inhibitor activity compared to an
ultrasonic bath system.
Ultrasonic-assisted hydrolysis at a power level of 150 W for
25 min treatment can be used to improve the antioxidant activities
of peanut protein (Yu et al., 2012). Ultrasound at an intensity of
0.707 W cm2 and frequency of 25 kHz was employed to produce
wheat gluten hydrolysates with enhanced iron-chelating, antioxidant and ABTS radical scavenging activities (Zhu, Su, Guo, Peng, &
Zhou, 2011). The same authors reported that molecular weight
distribution was strongly inuenced by ultrasonic frequency, being
lower in size when a lower frequency was applied. Peptides smaller
than 1 kDa possess the best antioxidant properties (Moure,
, 2006); thus the desirable production of low
Domnguez, & Parajo
molecular weight peptides can be facilitated using ultrasound.
3.4. Drug delivery
In general peptide based drugs are physically and chemically
unstable, have short in vivo half-lifes and have low oral bioavailability. Encapsulation of peptide based drugs with biodegradable
polymers can improve stability and bioavailability.
There are number of encapsulation techniques used for protein

65

drug delivery including ultrasonic atomization, electrospray, micro-uidic, pore-closing, thermo-reversible-gel, and microfabrication (Ye, Kim, & Park, 2010). Ultrasonic atomization is a
simple and continuous technique, and aseptic in nature (Ye et al.,
2010). Ultrasonic atomization is the process of breaking up of
thin lm of liquid into ne droplets when allowed to ow on a
vibrating surface (frequency >20 kHz). Capillary wave and cavitation are the two main hypotheses used to explain the mechanism of
liquid disintegration during ultrasonic atomization. The cavitation
hypothesis is generally applied to high frequency and high-energy
intensity systems. During the implosive collapse of cavities formed
during sonication, high intensity hydraulic shocks are generated.
These hydraulic shocks initiate the disintegration of the liquid lm
and cause direct ejection of the droplets (Avvaru, Patil, Gogate, &
Pandit, 2006). Various ultrasonic atomizer systems have been
developed over the years to produce protein microspheres (Freitas,
Rudolf, Merkle, & Gander, 2005; Yeo, Chen, Basaran, & Park, 2004).
Liposomes, composed of a lipid bilayer, are generally used as protein delivery carriers due to their robust and convenient nature to
deliver large protein molecules (Lu et al., 2010). However,
microbubble-enhanced ultrasound can be more efcient than liposomes for controlled release of proteins and peptides (Kinoshita
& Hynynen, 2005).
Sonophoresis is the use of ultrasound technology at a frequency
of 20 kHz-16 MHz and power intensity of up to 14 W cm2 to increase the penetration of molecules into and across the skin (Park,
Park, Seo, & Lee, 2014). Permeability of skin is enhanced by various
cavitational and non-cavitational mechanisms of ultrasound. In
high-frequency ultrasound (0.7e16 MHz) cavitation occurs within
the skin i.e. within cavities near the corneocytes of the stratum
corneum. However, low-frequency ultrasound (<100 kHz) uses
transient cavitation inside and outside the skin. Convection, thermal effects, mechanical or radiation pressure effects, lipid

MECHANISM

SOURCES

Chicken eggs,
Wheat, Corn,
Garlic, Milk,
Fish

KininKalicrein
System

ACE-Inhibitory
Pepdes

Substrate
Inhibitor
Prodrug

Producon
Tradional
- Protein hydrolysis by
using enzymes such as
pepsin, pancrean,
trypsin, chymotrypsin,
thermolysin, sublisin
and combinaons of
pepsin with other
enzymes

Ultrasound
- Improved dispersion and
less agglomeraon of
enzymes.
- Higher acvity
- Increased producon rates
- Probe ultrasound beer
than bath ultrasound
system

Fig. 5. Overview of ACE-Inhibitory peptides.

TYPES

ReninAngiotensin
System

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S.U. Kadam et al. / Trends in Food Science & Technology 46 (2015) 60e67

extraction and increase in the solution-membrane interfacial


transfer rate are some of the non-cavitational mechanisms of
sonophoresis (Polat, Hart, Langer, & Blankschtein, 2011). Lowfrequency ultrasound systems are under continuous commercial
development for transdermal delivery as they can be used to
enhance in vitro transdermal transport of many products including
insulin, erythropoietin, interferon and low-molecular weight heparin. Low-frequency ultrasound is more efcient than high frequency ultrasound due to increased incidence of cavitations and
high collapse pressure due to large size of bubbles (Prausnitz,
Mitragotri, & Langer, 2004). Mitragotri, Blankschtein, and Langer
(1995) successfully delivered insulin, interferon g and erythropoietin without any physical damage to skin or underlying muscle
tissue. Low-frequency ultrasound can be used to transport high
molecular weight drugs such as poly-L-lysine (Mol. weight 51 kDa)
due to a phenomena termed sonomacroporation (Weimann & Wu,
2002). Ultrasound combined with other methods, including
iontophoresis and electrophoresis enhances the efciency of drug
transport (Azagury, Khoury, Enden, & Kost).
4. Conclusions
Bioactive peptides have been widely researched because of their
abundant nature and diverse biological activities related to nutrition and health. The peptide drug market is also growing very
rapidly. However, commercial exploitation of bioactive peptides
remains challenging due to regulatory hurdles, low solubility in
water, fast clearance in the body and immunogenicity issues.
Recent research has shown that ultrasound can facilitate the production of bioactive peptides. USAED has been shown to facilitate
faster novel peptide preparation. UAE has been demonstrated to
achieve higher extraction yield and rates. In addition UAE also reduces solvent usage and results in minimal damage to thermolabile
peptides. Ultrasound also has applications in peptide drug delivery.
In summary, ultrasound is a robust and economically feasible option for the production and delivery of peptide drugs. Additional
research is required including scale up studies to facilitate the
adoption of ultrasound in the protein and peptide industries for
enhanced processing efciency and capability.
Acknowledgements
The authors acknowledge the nancial support from the Irish
Research Council's Embark Postgraduate Research Scholarship
Scheme.
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