Cells as Drug Carriers

Review Article

Austin J Nanomed Nanotechnol. 2014;2(3): 1017.

Cells as Drug Carriers

Arun Kumar*

Department of Medical Laboratory Sciences, University of Delaware, USA

*Corresponding author: Arun Kumar, Department of Medical Laboratory Sciences, Nanomedicine Research Laboratory, College of Health Sciences, University of Delaware, USA

Received: January 06, 2014; Accepted: March 17, 2014; Published: March 24, 2014


The biggest challenges in drug delivery are to transport the drug to the site of infection without degradation with high concentration and protect it from body’s immune system. In order to achieve these goals, it is important to have a better understanding of the cellular mechanisms and primary intracellular uptake systems and to figure out fate of nanomaterials in multifarious biological systems [1]. Most delivery systems suffer from one or another drawback such as rapid clearance by the immune system, low targeting efficiency and difficulty in crossing biological barriers [2]. The understanding of mechanisms underlying intracellular uptake is important to design nanomaterials for effective drug delivery. The most common drug delivery methods are injection, infusion, ingestion, and inhalation. The common ingestion systems are tablet, capsule or liquid formulations and inhalation systems use a dry powder inhaler, metered–dose inhaler (MDI) or a nebulizer. The challenges for both drug and drug delivery systems are to deliver a drug in such a manner that improves the benefits to the patients, healthcare personnel and the healthcare structure. The major challenges in drug delivery are: (i) Efficacy of drug and side effects, (ii) slow and sustained release, (iii) minimizing the pain from drug administration, (iv) increased ease of use, (v) increased use compliance, (vi) improved mobility, and (vii) decreased involvement of healthcare personals. Improved safety for healthcare personnel and minimization of the environmental impactby elimination of chlorofluorocarbon (CFC) is key to develop safe drug delivery methods. A number of approaches are being used tomeet these challenges [3,4]. The drug entered into cells was believed to be via diffusion through the lipid bilayer of the cell membrane, with the influence of transporter proteins. However, recent research has shown that the drug uptake is transporter–mediated [5]. This suggests that uptake transporters may be a major determinant of idiosyncratic drug response and a site at which drug–drug interactions occur. Precisely modeling of drug pharmacokinetics involves the knowledge of systems biology and transporters with which a drug interacts and where those transporters are expressed in the biological systems. The pharmacokinetic models, based on biophysical properties of the cells, allows for improved drug uptake by diffusion [6]. The incorporation of transporter protein delivery systems greatly improves cellular uptake of the drug [7]. Development of a new drug molecule is expensive and time consuming. Improving the safety and efficacy of existing drugshas been attempted using different methods such as individualizing drug therapy, dose titration, and therapeutic drug monitoring. Drug delivery at a controlled rate, with slow and sustained delivery, and targeted delivery are important to improve the cellular uptake of a drug. Nanoparticles and nanoformulations have been used by many researchers as safe and effective drug delivery systems and have greater potential for many applications including anti–tumors therapy, gene therapy, AIDS therapy, radiotherapy, protein delivery, antibiotics, virostatics, and vaccines [8].

Challenges in cellular drug delivery

In cellular systems membranes are major obstacles for drugs attempting to target intracellular structures. Drugs degrade while attempting to across biological membranes and it is directly related to the polarity of a drug molecule; nonpolar or lipophilic molecules easily bypass this complication with greater membrane penetration, generally via diffusion [9]. However, numerous other cellular processes such as endocytosis mechanisms, intracellular trafficking, and release of the drug directly affect the intracellular concentrations and effectiveness of the drug. However, many pharmaceutical agents, including many large molecules such as nucleic acids, proteins, enzymes, antibodies or drug–loaded pharmaceutical nanocarriers,need to be delivered intracellularly to exert their therapeutic action. Biological membranes prevent hydrophilic drug molecules from entering cells [10]. The intracellular transport of different biologicallyactive molecules is one of the major complications in drug delivery. Many compounds shows great potential in vitro studies but cannot succeed in vivo because of delivery problems. Several intracellular drug delivery systems were evaluated for their potential to transport therapeutic molecules inside cells and genome sequencing critically contributed in designing the drug delivery strategies. Significant advances were made with many efficient transfection reagents to study the gene functions. However, few nucleic acid intracellular delivery systems were developed for transfection, gene therapy, and delivery of other biomolecules [11].

Nanoparticles for cellular drug delivery

Nanoparticles are made up of natural or synthetic polymers ranging in size between about 10 and 1000 nm (1 mm). Drugs can be bound to nanoparticles or dispersed or adsorbed to the surface or can be chemically attached to it. Poly (butylcyanoacrylate) nanoparticles are successfully used for the in vivo delivery of drugs into the brain. This successful delivery to the brain uses hexapeptidedalargin (Tyr–DAla– Gly– Phe–Leu–Arg), and Leu–enkephalin analogue nanoparticleswith opioid activity [12]. Nanoparticles provide enormous advantages regarding drug targeting, delivery and release, and, with the potential to combine diagnosis and therapy, emerge as one of the major tools in nanomedicine. The main goals in using nanoparticles in drug delivery are to improve drug stability in the biological system, to mediate the bio–distribution, improve drug loading, targeting, transport and release, and efficiently cross the biological barriers. The major problems of nanoparticles are cytotoxicity, remaining degraded products, and biocompatibility. Liposomes are used in controlled drug delivery systems due their bio–adhesive and levonorgestrel properties. Mesophasicproliposomal systems were mostly unilamellar and some were multilamellar with zero order kinetics [13]. Alcohol as a polar molecule had greater effect on transdermal flux, and in vivo studies have shown that a significant lag phase observed before it reaches therapeutic levels. This proliposomes system is better thanPEG–based ointment systems [14] (Figure 1).

Citation: Kumar A. Cells as Drug Carriers. Austin J Nanomed Nanotechnol. 2014;2(3): 1017. ISSN:2381-8956