Breast milk-mediated drug delivery

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Breast milk-mediated drug delivery refers to the use of breast milk to transport a pharmaceutical compound, protein, or other treatment to achieve a desired effect. Delivery of these substances via milk provides an oral alternative for transport of a compound to the gut, specifically in infants. Breast milk-mediated drug delivery provides a way for pharmaceuticals and proteins to travel through the gastrointestinal system of an infant while minimizing the potential for irritation within gastrointestinal tissue.

Contents

Addition of compounds into breast milk

There are multiple routes that a treatment can enter into the breast milk. One route is through a breastfeeding mother. When a mother that is lactating receives a treatment including but not limited to prescription medication, over-the-counter medications, or herbal remedies, these compounds can make their way into the mother’s milk and are subsequently delivered to an infant via breastfeeding. [1] The amount of treatment transferred into the milk depends on the substance, but it is noted that these compounds can have an effect on the infant consuming the breast milk. [1]

A silicone nipple shield that could be loaded with a pharmaceutical compound Siliconen tepelhoedje - vorm na aanbrengen.JPG
A silicone nipple shield that could be loaded with a pharmaceutical compound

A common method for intended addition of treatment into breast milk involves the use of donor breast milk in combination with the compound of interest for treatment. Addition of antibiotics, oligosaccharides, cytokines, or selected proteins into donor breast milk for consumption can have a variety of effects on the patient consuming it, typically an infant. [2] [3] [4] This method has also been studied for use in adults, specifically for the delivery of poorly water-soluble drugs. [5] [6] While this method allows for the highest level of modularity among breast milk treatments, the effects of these treatments on various factors such as the microbiome of the milk base must be acknowledged to limit potential side effects.

Other novel technologies for drug delivery via breast milk involve the use of external objects to mediate the addition of compounds into the milk being consumed. One of these technologies is a nipple shield. A nipple shield is placed onto the nipple of a breastfeeding mother, releasing treatment into the milk as the mother breastfeeds an infant. [7] Many of these novel technologies still require testing for efficacy and safety before any potential commercial application.

Potential applications

Breast milk fortification

Breast milk fortification refers to the addition of nutrients such as proteins, oligosaccharides, or cytokines into breast milk to supplement the natural contents of the milk. [2] [3] [4] This practice is common in babies that have been born prematurely, with a major goal of this practice being growth promotion. [8] These infants do not receive enough nutrients for proper growth and development from a normal breastfeeding regimen, potentially leading to neural and/or cognitive impairment. [8] [9] Thus, supplementation of breast milk with proteins, calcium, phosphate, and other nutrients can help to remedy this issue. [8] [9]

Studies have shown that human milk fortification can improve the short-term growth of infants, though future research is needed to determine long term growth effects. [10] There is variation with results from case to case, however. The nonstandard concentration of proteins across different mothers’ breast milk can lead to issues when pinpointing the amount of nutrients an infant is receiving. [8] While there is a standard fortification level used in most cases, “Adjustable Fortification and “Targeted Fortification” are being researched as ways to provide targeted individual fortification to suit the needs of each individual being treated. [8]

One particular compound that can be used to fortify breast milk is Human Milk Oligosaccharide. These prebiotics are found naturally in human breast milk, and provide a variety of health benefits to newborns, including modulation of the immune system, fighting viral infections, and promoting epithelial cell maturation. [3] These prebiotics, which have been confirmed to be safe and tolerable for infants, are a leading candidate for breast milk fortification.

Antibiotic addition

Antibiotics can be added into breast milk as a preventative measure for the development of infections such as Subsequent Late Onset Sepsis and Necrotizing Enterocolitis. [11] Antibiotic treatment is a very common treatment for premature babies, though dosing regimen and treatment length tend to be “arbitrary”. [11] While potentially detrimental to the health of the gut microbiome if given in excess, the administration of antibiotics within breast milk can help to prevent infection in newborns. [12]

Antibiotics are used as the most common treatment for prematurely born infants in Neonatal Intensive Care Units – used as a preventative measure for infection. These treatments usually contain empirical antibiotics and are often given to infants that do not show signs of bacterial infection. [13] Studies are currently being performed to determine the optimal length of treatment for infants to prevent infection while maintaining gut health, specifically in the microbiome. [11] [12] [13]

Stability of milk-drug formulations is another factor that contributes to the effectiveness of antibiotic addition into breast milk. Many orally delivered antibiotics show poor solubility in aqueous environments, leading to increased research into lipid-based drug delivery systems. [6] Milk formulations, which contain varying levels of natural lipids, have been shown to increase delivery efficacy of antibiotic compounds, while maintaining stability and integrity of the colloidal structure that makes up milk. [6]

Prevention of necrotizing enterocolitis

Depiction of Necrotizing Enterocolitis Histopathology Necrotizing enterocolitis histopathology.jpg
Depiction of Necrotizing Enterocolitis Histopathology

Addition of carefully selected compounds into breast milk have been shown to not only stimulate growth within an infant, but also help to prevent infections from forming, specifically in the gut. Babies born very prematurely are at high risk for these infections, particularly necrotizing enterocolitis. [14] Necrotizing enterocolitis is an intestinal condition that develops in some premature babies, and is characterized by inflammation, bacterial infection, potential intestinal injury, and in extreme cases, death. [13]

The development of necrotizing enterocolitis has also been linked to the microbiome of the gut in the affected population. [11] [12] High levels of antibiotic administration have been shown to reduce the variety of bacteria present within the gut microbiome, and this lower level of diversity found in these infants can increase their susceptibility to necrotizing enterocolitis. [11] Studies have indicated that time of administration of antibiotics as well as type of antibiotic can impact the incidence of the condition. [12]

Prevention of necrotizing enterocolitis in premature infants is mainly achieved through the addition of predetermined compounds into donor breast milk that is fed to premature infants at risk for the condition. Compounds such as immunoglobulins have been shown to reduce Necrotizing Enterocolitis incidence, as well as severity in those that still develop the condition. [2] Studies have shown that the addition of IgA and IgG into a premature infant’s feed can lower the incidence of the disease in the population of infants that are at the highest risk for the condition (very premature, low birth weight). [2]

Problems

One of the main issues surrounding breast milk-mediated drug delivery is the uncertainty of the composition of the milk acting as the vessel for the treatment. Since every breastfeeding mother experiences different external conditions such as diet and environment, as well as differences in genetics, breast milk from every mother will have a different composition, making it difficult to create replicable treatments from infant to infant. [8] Donor breast milk encounters this same issue, with infant formula acting as a potential avenue for stabilization of treatment levels.

Improper administration of antibiotics into an infant’s gastrointestinal system can increase the susceptibility of infants to gut infections. This is due to the lowered diversity and viability of organisms found within the gut, also known as the microbiome. [11] [12] Especially prevalent in preterm infants, this deviation from a healthy microbiome can lead to adverse effects during the beginning of an infant’s life. These infants may be predisposed to conditions such as Necrotizing Enterocolitis due to higher growth of pathogenic bacteria within the gut, as well as a lower count of commensal bacteria growth. [11]

Future prospects

New breast milk-mediated therapies are still in development, aiming to take advantage of properties that are unique to this form of treatment. One such technology is the use of exosomes found in milk to transport molecules such as mRNA, DNA, and proteins to an area of interest. [15] This research proposes the use of milk as a scalable source of exosomes for a method of targeted drug delivery with higher efficacy than standard oral methods. [15] These novel therapies may provide a way to achieve a low-cost method to deliver drugs with poor water solubility into the body, with potential use as a low-cost alternative. [5]

See also

Related Research Articles

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<span class="mw-page-title-main">Breast pump</span> Mechanical device used to extract milk from human breasts

A breast pump is a mechanical device that lactating women use to extract milk from their breasts. They may be manual devices powered by hand or foot movements or automatic devices powered by electricity.

<span class="mw-page-title-main">Mastitis</span> Medical condition

Mastitis is inflammation of the breast or udder, usually associated with breastfeeding. Symptoms typically include local pain and redness. There is often an associated fever and general soreness. Onset is typically fairly rapid and usually occurs within the first few months of delivery. Complications can include abscess formation.

<span class="mw-page-title-main">Preterm birth</span> Birth at less than a specified gestational age

Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between 28 and 32 weeks, early preterm birth occurs between 32 and 36 weeks, late preterm birth is between 34 and 36 weeks' gestation. These babies are also known as premature babies or colloquially preemies or premmies. Symptoms of preterm labor include uterine contractions which occur more often than every ten minutes and/or the leaking of fluid from the vagina before 37 weeks. Premature infants are at greater risk for cerebral palsy, delays in development, hearing problems and problems with their vision. The earlier a baby is born, the greater these risks will be.

<span class="mw-page-title-main">Breast milk</span> Milk produced by the mammary glands in the breast of a human female

Breast milk or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates and variable minerals and vitamins. Breast milk also contains substances that help protect an infant against infection and inflammation, whilst also contributing to healthy development of the immune system and gut microbiome.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease that affects premature or very low birth weight infants. Symptoms may include poor feeding, bloating, decreased activity, blood in the stool, vomiting of bile, bowel death, multiorgan failure, and even death.

<span class="mw-page-title-main">Prelabor rupture of membranes</span> Medical condition

Prelabor rupture of membranes (PROM), previously known as premature rupture of membranes, is breakage of the amniotic sac before the onset of labor. Women usually experience a painless gush or a steady leakage of fluid from the vagina. Complications in the baby may include premature birth, cord compression, and infection. Complications in the mother may include placental abruption and postpartum endometritis.

<span class="mw-page-title-main">Chorioamnionitis</span> Medical condition

Chorioamnionitis, also known as intra-amniotic infection (IAI), is inflammation of the fetal membranes, usually due to bacterial infection. In 2015, a National Institute of Child Health and Human Development Workshop expert panel recommended use of the term "triple I" to address the heterogeneity of this disorder. The term triple I refers to intrauterine infection or inflammation or both and is defined by strict diagnostic criteria, but this terminology has not been commonly adopted although the criteria are used.

Gray baby syndrome is a rare but serious, even fatal, side effect that occurs in newborn infants following the accumulation of antibiotic chloramphenicol. Chloramphenicol is a broad-spectrum antibiotic that has been used to treat a variety of bacteria infections like Streptococcus pneumoniae as well as typhoid fever, meningococcal sepsis, cholera, and eye infections. Chloramphenicol works by binding to ribosomal subunits which blocks transfer ribonucleic acid and prevents the synthesis of bacterial proteins. Chloramphenicol has also been used to treat neonates born before 37 weeks of the gestational period for prophylaxis purposes. In 1958, newborns born prematurely due to rupture of the amniotic sac were given chloramphenicol to prevent possible infections, and it was noticed that these newborns had a higher mortality rate compared with those who were not treated with the antibiotic. Over the years, chloramphenicol has been used less in clinical practices due to the risks of toxicity not only to neonates, but also to adults due to the risk of aplastic anemia. Chloramphenicol is now reserved to treat certain severe bacteria infections that were not successfully treated with other antibiotic medications. Signs and symptoms are summarized in the WHO Model Formulary for Children 2010 under the rare adverse effect section of chloramphenicol.

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<span class="mw-page-title-main">Breastfeeding difficulties</span> Medical condition

Breastfeeding difficulties refers to problems that arise from breastfeeding, the feeding of an infant or young child with milk from a woman's breasts. Although babies have a sucking reflex that enables them to suck and swallow milk, and human breast milk is usually the best source of nourishment for human infants, there are circumstances under which breastfeeding can be problematic, or even in rare instances, contraindicated.

<span class="mw-page-title-main">Breastfeeding</span> Feeding of babies or young children with milk from a womans breast

Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be pumped and fed to the infant. The World Health Organization (WHO) recommends that breastfeeding begin within the first hour of a baby's life and continue as often and as much as the baby wants. Health organizations, including the WHO, recommend breastfeeding exclusively for six months. This means that no other foods or drinks, other than vitamin D, are typically given. WHO recommends exclusive breastfeeding for the first 6 months of life, followed by continued breastfeeding with appropriate complementary foods for up to 2 years and beyond. Of the 135 million babies born every year, only 42% are breastfed within the first hour of life, only 38% of mothers practice exclusive breastfeeding during the first six months, and 58% of mothers continue breastfeeding up to the age of two years and beyond.

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<span class="mw-page-title-main">Neonatal infection</span> Human disease

Neonatal infections are infections of the neonate (newborn) acquired during prenatal development or within the first four weeks of life. Neonatal infections may be contracted by mother to child transmission, in the birth canal during childbirth, or after birth. Neonatal infections may present soon after delivery, or take several weeks to show symptoms. Some neonatal infections such as HIV, hepatitis B, and malaria do not become apparent until much later. Signs and symptoms of infection may include respiratory distress, temperature instability, irritability, poor feeding, failure to thrive, persistent crying and skin rashes.

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<span class="mw-page-title-main">Human milk microbiome</span> Community of microorganisms in human milk

The human milk microbiota, also known as human milk probiotics (HMP), refers to the microbiota (community of microorganisms) residing in the human mammary glands and breast milk. Human breast milk has been traditionally assumed to be sterile, but more recently both microbial culture and culture-independent techniques have confirmed that human milk contains diverse communities of bacteria which are distinct from other microbial communities inhabiting the human body.

<span class="mw-page-title-main">Human milk immunity</span> Protection provided to immune system via human milk

Human milk immunity is the protection provided to the immune system of an infant via the biologically active components in human milk. Human milk was previously thought to only provide passive immunity primarily through Secretory IgA, but advances in technology have led to the identification of various immune-modulating components. Human milk constituents provide nutrition and protect the immunologically naive infant as well as regulate the infant's own immune development and growth.

References

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