development and characterization of casein-based micro- and nano
TRANSCRIPT
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Development and characterization of casein-based micro- and nano-carriers as promising drug delivery vehicles.
OR
Making medicines better with novel micro- and nano-carriers.
Instructor: Turovsky Tanya Department of Biotechnology and Food Engineering
Abstract
There are many ways to deliver drugs into the body. Taking drugs by the mouth (orally)
is the most widely used form of drug administration because of its simplicity,
convenience, and patient acceptance, especially in the case of repeated dosing for
chronic therapy. The importance of oral drug delivery also demonstrates itself in that it
comprises the largest fraction of all marketed drugs today. However, the majority of
current drugs are characterized by low water solubility, a property that leads to severe
drawbacks, such as poor and variable bioavailability. Increasing aqueous solubility of
drugs is therefore a key for successful drug design and researchers are seeking ways to
incorporate various technologies in oral formulations. For example, many
developments concentrate on encapsulation of drugs into vehicles, e.g., polymeric
capsules, micelles, liposomes and other structures (Figure 1a). Such vehicles are
designed to deliver the drug to its target site and release it there.
The present research project suggests the utilization of casein for the design and
construction of a novel vehicle for oral delivery of poorly water-soluble drugs. Casein
is the major protein in milk, where it is found as a suspension of particles called "casein
micelles" (Figure 1b). It has many desirable properties as a drug delivery vehicle: it is
inexpensive, readily available, non-toxic and highly stable. Owing to its natural food
source, this GRAS (generally recognized as safe) protein is biocompatible and
biodegradable. Moreover, casein is natively designed as an efficient delivery vehicle;
in nature it serves to transport nutrients from mother to infant. With its unique
characteristics, casein is a great candidate for the preparation of conventional and novel
drug delivery systems.
Figure 1. (a) Diagrammatic representation of various types of carriers for oral drug delivery (b) A casein micelle; A: a
submicelle; B: protruding chain; C: Calcium phosphate; D: κ-casein; E: phosphate groups
a b
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The leading concept is to utilize the unique properties of the protein to stabilize,
encapsulate, and protect poorly water-soluble drugs, and administer the drug-loaded
system orally. Then, relying upon spontaneous digestion of the milk protein (thus
without a need for sophisticated mechanisms) the drug is expected to be released along
the intestine wall. While the research is driven by the motivation to improve
bioavailability of poorly soluble drugs, here a study of a fundamental character is
proposed, aiming to first gain deep understanding of the inherent properties. This will
involve important techniques as drug-loading and drug-release, and utilization of basic
equipment as the light microscope, and advanced equipment as the electron microscope.
Student mission / Objective:
The main objective is to develop a stable casein-based carrier for oral delivery of poorly
water-soluble drugs. This aim may be divided into three steps as follows:
1. Drug encapsulation in different compositions and basic characterization of the
obtained drug vehicles.
2. Identification of the potential formulations, their further development and
optimization, and deeper characterization.
3. Identification of the most promising drug vehicle and determination of its drug
release profile; comparison between the release profile of drug when
encapsulated in the developed vehicle and when not encapsulated.
During the project, students will experience in:
Basic laboratory procedures, such as preparation of simple solutions and use of
the analytical balance, the pH meter, the centrifuge, the magnetic stirrer, the
spectrophotometer, the dry bath incubator and the water bath incubator.
Advanced laboratory skills and techniques:
- Use of light microscope
- Use of high-resolution scanning electron microscope (HR-SEM), including
experience in sample preparation
- Use of freeze-dryer, including experience in sample preparation
Fundamental techniques in the development of drug carriers:
- Drug loading procedure
- Strategies for identification and selection of good drug-loaded candidates
- Strategies for platform optimization
- Preparation of a calibration curve
- Determination of in-vitro drug release profile
- Strategies to improve formulation stability and shelf-life
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Requirements:
Knowledge of chemistry at a good level (5 units/college)
Knowledge of math at a basic level
Knowledge of microsoft office at a basic level
"Good hands" for lab work
Paper name:
Casein-based formulations as promising controlled release drug delivery systems
Questions about the paper:
1. What are the advantages of milk proteins for the delivery of bioactive
molecules?
2. Describe the casein micelle structure
We will discuss the answers when we meet at the dinner in the opening ceremony.
Please feel free to contact me with questions regarding the project at
Recommended reading material:
Livney, Yoav D. "Milk proteins as vehicles for bioactives." Current Opinion
in Colloid & Interface Science 15.1 (2010): 73-83.
Semo, Efrat, et al. "Casein micelle as a natural nano-capsular vehicle for
nutraceuticals." Food Hydrocolloids 21.5 (2007): 936-942.
Zimet, Patricia, Dina Rosenberg, and Yoav D. Livney. "Re-assembled casein
micelles and casein nanoparticles as nano-vehicles for ω-3 polyunsaturated
fatty acids." Food Hydrocolloids 25.5 (2011): 1270-1276.