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The critical impact of controlled drug delivery in the future of tissue engineering.

In classic drug delivery, simple and fast acting response through different delivery routes such as oral or injection has been achieved [1]. The cost and complexity of classic delivery of drugs resulted in the inhibition of these conventional techniques. The concept of controlled drug delivery was first introduced as a part of pharmaceutical industry via Wurster technique in 1949 and experienced Coacervation (liquid encapsulation) from 1953, offering microencapsulation technology in 1960 as a milestone in this progress [2]. This led an extreme application of microencapsulation technics in over 60% of all current drugs. This approach was continued by implants invention in 1970, transdermal delivery in 1980 and was developed with site directed systems in 1990 [2]. The development of controlled drug delivery as a successful strategy has been recently formed due to many complicated challenges in classic drug delivery systems like drug potency reduction, toxic level of release and costs associated with long term drug doses [1]. Moreover, oral administration of drugs could potentially result in disorderly pharmacokinetics, since these agents might have different effects on the metabolic pathways of the body [3]. This can result in larger than necessary doses being administered, which can further cause increased toxicity [4]. The traditional intravenous routes are often even more problematic. It is also known that the specificity of some conventional intravenous drugs is very low, which could be harmful for the healthy tissues. Therefore, nanoparticle-based drug delivery as an alternate approach provides more efficient solutions to overcome some of these problems. It was first in 1975 that Ringdorf suggested a polymer-drug conjugate model that could enhance the delivery of drugs [5].Controlled drug delivery systems are known as biocompatible carriers, allowing high payloads of drug molecules, preventing premature drug release with site specific targeting potential, and drug releasing at a controlled rate to reach effective local drug concentrations in the range of therapeutic level with minimum possible side effects [6].The multiplicity in compositions, properties and structures in polymers has made them the main material in drug delivery in the range of micro and nano carriers as capsules, micelles and dendrimers[7]. The controlled delivery of an active pharmaceutical ingredient by polymeric nanoparticlesis obtained with the specific property of controlled release of a drug over a prolonged period without renewal dosing [8,9].To achieve the required specific combination properties a plethora of polymeric materials have been usually proposed [10]. During the last few years, a new field of drug delivery systems based on nanomaterials science has emerged. These novel systems have had a significant impact on localized, safe and effective drug delivery. Annual sale of these drug delivery systems alone in the United States is about $30 billion, which is probably more than two times worldwide [11]. Diffusion of water in the polymeric matrix is considered as the first step in drug release. Polymer hydrolysis in controlled biodegradable drug delivery system is taken into account as a main degradation mechanism whereas microbial, enzymatic, and thermal degradation may occur in some cases [12]. In the body, chemical hydrolysis of nanoparticles begins with water uptake, followed by hydrolytic cleavage of the bonds, under the influence of different factors such as chemical structure, crystallinity and hydrophobicity, molecular weight, purity, morphology, processing method, etc. [13].Despite the fact that, the controlled release is related to biodegradation, removal of the carrier of the drug molecules is considered as another key point of biodegradable systems [14]. Therefore, among all the polymers available for drug delivery applications, biodegradable polymers are highly recommended.

Tissue engineering is known as a newly emerged strategy to repair and regenerate the injured or deficient tissues through natural, synthetic biodegradable porous constructs as scaffolds. The combination of biomaterials, cells, and biological molecules to induce differentiation signals to promote tissue repair is shown in tissue engineering as a promising therapeutic approach [15]. The combination of tissue engineering and controlled drug delivery has been shown as an effective strategy for locally controlling the dose and duration of the release of biological molecules [6]. Indeed, dual application of biodegradable polymers as a porous substrate for cell adhesion, proliferation and differentiation and also as a controlled drug release system for the local tissue has led to be a valuable achievement in both tissue engineering and drug delivery aspects. Transferring active pharmaceutical ingredients to the site defects in the body by biodegradable polymeric nanocarriers, owning their unique physicochemical properties is the goal of this approach [16]. These therapeutic nanoparticles have the potential to revolutionize the drug development process and change the landscape of tissue engineering and regenerative medicine [17-21]. Application of polymeric carriers in nano size has led to develop a new achievement to better control on different types of biological molecules such as hydrophilic drugs, hydrophobic drugs, antibiotics, growth factors, proteins, and nucleic acids [22]. In addition, many factors such as the physicochemical properties of the nanoparticles, morphological characteristics, type of the defected tissues, the rate of blood flow, and vascular supply, play critical roles in determining the effectiveness of this strategy [23]. In order to revolutionize the delivery mechanisms of biological molecules to the targeted tissues or organs, development of highly improved nanocarriers with enhanced biocompatibility and biodegradability properties is needed [24].


There have been several attempts to generate new treatments for defected tissues. Many tissue engineering strategies have been proposed but the field is still in its fancy stages and needs further developments. This note suggested a major strategy for creating the next generation of scaffold constructs along with the approaches taken to incorporate biological molecules within the nanoparticles and the benefits of combining tissue engineering and drug delivery.

Masoud Mozafari

Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), P.O. Box 14155-4777, Tehran, Iran E-mail:

Received 18 June 2014; Accepted 19 June 2014; Available online 1 July 2014


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Author:Mozafari, Masoud
Publication:Trends in Biomaterials and Artificial Organs
Article Type:Report
Date:Jul 1, 2014
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