Curt’s Cannabis Corner: What is Nanoemulsion Technology? Part 2

Welcome to the third installment in the series of educational articles from technical writer Curt Robbins at Higher Learning LV and MJBA’s MJNews Network. This collection is intended for cannabis and hemp industry professionals who wish to gain a better understanding of the nuanced biochemistry of this specialand newly legalherb. 

For the past two weeks, Curt has been teaching readers about the hot new manufacturing process for cannabis- and hemp-infused products called nanoemulsion

What is nanoemulsion? How can it help patients and consumers while offering additional marketing opportunities for entrepreneurs? How does it compare to traditional formulation technologies? Read on to learn!


CURT’S

CANNABIS

CORNER 

What is Nanoemulsion Technology?

Part 2

By Curt Robbins

 

 

Read What is Nanoemulsion Technology?: Part 1. In Part 1, readers learn the definition of nanoemulsion and how it is being employed in the cannabis and hemp industries for the creation of consumer products that feature enhanced bioavailability (including greater potency and faster onset). This formulation tech also allows more accurate dosing, a large advantage to millions of patients and their caretakers. 

In Part 2, let’s dive deeper into this excerpt from the Higher Learning LV course Cannabis Core Concepts by further exploring bioavailability issues, examining some real world metrics, and learning the latest scientific research about nanoemulsion technology! 

End Game: Increased Bioavailability

The purpose of packaging a medicine, wellness tonic, or lifestyle beverage in the form of a nanoemulsion is straightforward: To improve bioavailability. This includes not only greater potency, but also faster onset. 

Onset is an important issue for consumers who require quick relief from conditions such as chronic pain, nausea, seizure activity, and social anxiety, to name only a few. Most within this population cannot tolerate the approximately two-hour wait that characterizes the onset of standard infused edible products (especially given that peak potency requires an additional one to three hours). 

The exact onset period of a particular nanoemulsion depends on several factors, including consumption avenue and the biophysical circumstances under which it is consumed by users. This includes their age, relative health, genetic makeup, medical history, and use of commingling drugs.  

Edible cannabis products formulated with nanoemulsions typically involve an onset period of roughly 10-30 minutes, with 15-20 minutes being a common claim among companies offering infused beverages and edibles featuring nanoencapsulated cannabinoids and terpenes.   

A 2014 study entitled “Enhancement of the Oral Bioavailability of Breviscapine by Nanoemulsion Drug Delivery System” that was published in the journal Drug Development and Industrial Pharmacy explored the ability of a “nanoscale drug delivery system to realize the improvement of its oral bioavailability.” 

Reported the study, “the relative bioavailability of [the nanoencapsulated drug] reached 250 percent.” The researchers concluded that the nanoemulsion enhanced the oral absorption of [the drug] due to “improved stability and permeation.”  

A 2017 study entitled “Nanoemulsion-based Delivery System for Enhanced Oral Bioavailability” that was published in the journal Drug Delivery investigated the relative bioavailability of various formulation approaches, including nanoemulsion. “Nanoemulsion of BBH showed a relative bioavailability of 440 percent compared with unencapsulated BBH.” The study’s authors also reported that the nanoencapsulated liquid remained stable following a six-month evaluation period.  

If performed properly and depending on the exact compounds involved, nanotechnology can result in faster onset and greater potency at lowerand significantly more accuratedoses. This approach offers not only more efficient treatment of conditions such as pain and seizures, but also the economy resulting from smaller volumes of a particular compound or drug that yield greater potency.

Detailed Definitions

Research has revealed that bioavailability of cannabinoids such as CBD and CBG may be increased from as low as six percent in traditional, non-nanoemusified preparations (revealed by this study) to as great as 90 percent with nanoemulsified products (demonstrated by another study). 

According to a 2010 study entitled “Nanoemulsion: A Pharmaceutical Review,” nanoemulsion-based products are “by far the most advanced nanoparticle systems for the systemic delivery of biologically active agents for controlled drug delivery and targeting.” The study noted that nanoemulsion droplet sizes within a particular sample, when accomplished successfully, feature “narrow size distributions” (variance).  

“Nanoemulsions are the thermodynamically stable isotropic system in which two immiscible liquids (water and oil) are mixed to form a single phase by means of an appropriate surfactant [or emulsifying agent] or its mix with a droplet diameter in the range of 0.5-100 nm,” reported the study’s authors. The research concluded that “nanoemulsion shows great promise for the future of cosmetics, diagnostics, drug therapies, and biotechnologies.”

According to a 2014 study published in the journal 3 Biotech, a nanoemulsion is a “fine oil/water or water/oil dispersion” featuring a droplet size range of 20–600 nm. The study explained that three primary types of nanoemulsions exist: “(a) oil in water nanoemulsion in which oil is dispersed in water, (b) water in oil nanoemulsions in which water droplets are dispersed in oil, and (c) bi-continuous nanoemulsions.”

Nanoemulsion Research Studies

Although a relatively new technology, serious peer-reviewed research reports have begun to emerge regarding nanoemulsions. These study results consistently demonstrate significantly greater bioavailability, including shorter onset periods and enhanced peak potency. Nanoemulsion tech has shown this effect for a variety of cannabis-derived compounds, including CBD.

A 2016 study entitled “Nanoemulsions: Formation, Properties, and Applications” that was published in the journal Soft Matter noted a number of advantages to the use of nanoemulsion technology for delivery of drugs, including a small size that “leads to useful properties such as high surface area per unit volume, robust stability, [and] optically transparent appearance.” 

The research also noted the different forms of drug delivery in which nanoemulsion technology can improve bioavailability, which include “topical, ocular, intravenous, internasal, and oral delivery.” 

The study reported that most nanoemulsions are transparent in appearance because the droplet size employed “is significantly smaller than the wavelength of visible light.” However, the researchers noted that product and drug formulators “can easily tune the appearance of nanoemulsions to range from transparent to milky white” through the adjustment of droplet size. 

A 2017 study entitled “Biocompatible Nanoemulsions Based on Hemp Oil and Less Surfactants for Oral Delivery of Baicalein with Enhanced Bioavailability” that was published in the International Journal of Nanomedicine aimed to “probe the potential of nanoemulsions consisting of hemp oil in ameliorating [improving] the oral bioavailability of [the flavonoid] baicalein.” 

The study involved a particle size of 90 nm and an impressive bioavailability (what the study called an “entrapment efficiency”) of 99.31 percent. It reported that the flavonoid’s oral bioavailability was increased by “up to 524.7 percent and 242.1 percent relative to the suspensions and conventional emulsions, respectively.” 

The research determined that the safety profile of the flavonoid-based nanoemulsion revealed safe oral consumption. “Our findings suggest that such a novel…preparative process provides a promising alternative to current formulation technologies” and that nanoencapsulation is suitable for “oral delivery of drugs that feature…bioavailability issues.”

A 2017 study entitled “Nanoemulsion: A Novel Eon in Cancer Chemotherapy” that was published in the journal Mini Reviews in Medicinal Chemistry investigated the role of nanoemulsions in the effective treatment of cancer. 

The study’s authors observed that nanoemulsions offer a new approach to improving the sometimes poor bioavailability issues that have plagued traditional preparations and formulations for generations. Reported the study, “the research fraternity has acknowledged nanoemulsions as…capable of effectively addressing the low bioavailability…issues associated with conventional anticancerous chemotherapeutic dosage forms.”

A 2019 study entitled “Development of a Novel Nano­emulsion Formulation to Improve Intestinal Absorption of Cannabidiol” that was published in the journal Medical Cannabis and Cannabinoids observed the relatively poor bioavailability of CBD when ingested orally. “Cannabidiol (CBD) is highly lipophilic [fat loving] and its oral bioavailability is known to be very low in humans.” 

The study developed a novel nanoemulsion preparation of CBD involving a droplet size of approximately 35 nm “to improve the poor solubility and absorption of CBD.” The research reported that significant improvements in bioavailability were afforded by the nanoemulsification process. The period to achieve peak bioavailability (delay from time of consumption) was shortened by 330 percent and its potency was increased by 65 percent compared to a traditional non-nanoemulsified CBD oil. 

The study’s authors observed that their research was “the first to develop a CBD-based nanoemulsion formulation for testing,” which they observed to “extensively enhance the absorption of CBD and improve its bioavailability.”

A 2019 study entitled “Quercetin Loaded Nanoemulsion-based Gel for Rheumatoid Arthritis” that was published in the journal Biomedicine & Pharmacotherapy explored the advantages of a nanoemulsified topical application for the treatment of arthritis. 

The study found the nanoemulsified gel to feature improved bioavailability and “confirmed adequate rheological behavior with a good texture profile and improved drug permeation.” The report’s authors concluded that the nanoemulsified gel featuring the flavonoid quercetin “is an efficient topical treatment strategy for rheumatoid arthritis.” 

A 2019 study entitled “Emulsiogenesis and the Emergence of Nanoemulsions” that was published in the journal Matter investigated “the origin of the first natural emulsions and the evolution in production, classification, and nomenclature of extremely fine colloidal emulsions.”

The study reported that the first emulsions in nature appeared without the help of homo sapiens (and long before their appearance on the planet), about three to four billion years ago. It detailed how the emergence of waterborne microbes “produced organic hydrocarbon molecules, which were large enough in molar mass that collections of [them] formed liquid oil droplets surrounded by water.”

The researchers explained how the history of human-crafted emulsions dates back more than one hundred years. “Small-scale emulsions have been the subject of serious scientific investigations for more than a century, leading to very important milestones in condensed matter.”

The study emphasized how nanoemulsion tech remains in its infancy and that future developments will lead to novel and commercially enticing methods of encapsulating particular types of molecules for storage, distribution, and consumptionall while maintaining maximum bioavailability. 

“Regardless of the trends in nomenclature used for classifying emulsions, it is clear that emulsions having the smallest attainable droplet sizes, increasingly complex chemical compositions, and even multiple internal compartments represent a fertile area for basic research and important applications over many decades to come,” concluded the study’s authors. 

It’s a Wrap

Nanoemulsion technology offers patients and lifestyle consumersand the companies that serve thema way to encapsulate wellness molecules such as CBD, CBG, and THC that features improved stability and greater bioavailability than more traditional formulation techniques, including standard oils and liposomes. 

Heavily regulated industries such as hemp and cannabis benefit significantly from products that are formulated in a manner that leads to maximum shelf life and that can ensure sometimes lengthy storage periods. Greater bioavailability, in turn, offers both lifestyle consumers and multiple patient populations the advantage of rapid onset and enhanced potency. Medical professionals and caretakers are demonstrating an affinity for nanoemulsions based on not only enhanced bioavailability, but also more accurate dosing.   

Copyright © 2021 Higher Learning LV™. All Rights Reserved. 

Nanoparticle Drones To Target Lung Cancer with Radiosensitizers And Cannabinoids

imageWilfred Ngwa1,2*, imageRajiv Kumar1,3imageMichele Moreau1,2imageRaymond Dabney4 and imageAllen Herman4

1Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
2University of Massachusetts Lowell, Lowell, MA, United States
3Northeastern University, Boston, MA, United States
4Cannabis Science Inc., Irvine, CA, United States
 
CALIFORNIA: Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. Smart nanomaterials (nanoparticle drones) can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous (“sea”) routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

Introduction

Nanomedicine, the application of nanotechnology to medicine, has opened a new, previously unimaginable world in cancer diagnosis and therapy. Today new multifunctional nanoplatforms or smart nanomaterials (nanoparticle drones) can be constructed and endowed with image contrast enhancement capabilities for techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) (12) and can contain therapeutic payloads programmed for targeted delivery to disease sites (3). The vision of combining diagnostics and therapeutics, now being referred to as theranostics, was considered futuristic only a few years ago but is now clearly achievable—the future is almost now!

A) Cartoon showing both intravenous and inhalation (INH) delivery of nanoparticle drones; (B) TEM image of lung tumor targeted with drones; (C) absorption spectra of drone technology uniquely customized for INH delivery to lung tumors.

A) Cartoon showing both intravenous and inhalation (INH) delivery of nanoparticle drones; (B) TEM image of lung tumor targeted with drones; (C) absorption spectra of drone technology uniquely customized for INH delivery to lung tumors.

Recognizing the potential impact of nanomedicine, the National Cancer Institute created the Alliance for Cancer Nanotechnology to leverage the potential of nanotechnology toward transforming the way cancer is diagnosed, treated, or prevented. Projects funded by this Alliance have led to significant research breakthroughs and have even entered successful clinical trials (4). Today, cancer nanomedicine now includes burgeoning research and development in nanoparticle-aided radiotherapy (NRT). A recent article (5) provides a robust review of NRT developments for over a decade in NRT with gold nanoparticles (GNPs), highlighting emerging approaches, challenges, and opportunities for further research toward clinical translation. Beyond GNP, other research has highlighted the use of alternative nanoparticle platforms like gadolinium nanoparticles (67), hafnium nanoparticles (8), platinum-based chemotherapy drug platforms, and others with theranostic capability (910).

In general, the key goal for NRT and cancer drug development efforts is the same, which is to optimize therapeutic efficacy/ratio. To this end, recent advances in the design of smart nanomaterials proffer tremendous potential toward realizing this goal. Such smart materials (11) are specifically designed to be sensitive to a specific stimulus, such as temperature, magnetic field, ultrasound intensity, light or radiation, and pH, and to then respond in active ways including radiosensitization or changing their structure for drug delivery, or other functions that have the potential to cogently enhance treatment outcomes.

Gold nanoparticles provide an excellent template for building such nanoparticle drones. They are biocompatible radiosensitizers (5), proffering relatively no toxicity. They can readily interact with photons by the photoelectric effect, to emit missile-like photoelectrons or Auger electrons in the micrometer range, to substantially boost RT damage to cancer cells. In the photoelectric effect, photons interact with the nanomaterials, with the probability of photoelectric interaction inversely proportional to the cube of the photon energy (5). Once the photoelectron is emitted, this creates a vacancy that may be filled by an electron from a higher energy level. The resulting release of energy could then also knockout Auger electrons. The Auger electrons are shorter range and with high linear energy transfer, so can lead to highly localized damage. Such highly localized damage to tumor cells can allow minimization of the primary radiotherapy dose and hence normal tissue toxicity. Nanoplatforms such as GNPs are also particularly attractive for building nanoparticle drones because they can provide CT and photoacoustic imaging contrast and are suitable for drug loading and attaching targeting moieties. Depending on surface functionalization, type of drug, and desired application, GNPs can be easily loaded with drugs or other molecules through either non-covalent interactions or covalent conjugation. Loading of drugs onto GNPs may improve their stability and biodistribution in biological media since the drugs are protected in the carrier. In short, multifunctional nanoparticle drones based on GNPs hold great promise in cancer nanomedicine.