Current Nanomedicine - Volume 6, Issue 2, 2016

Background: An effective drug delivery system delivers the therapeutically active moieties at the right time, rate and in a reproducible manner to effectively target sites for human illnesses. A major limitation associated with most of the currently available conventional and controlled release drug delivery devices is that not all the drug candidates are well absorbed uniformly locally or systemically. Methods: We searched for recent technological advancements in the development of nano-structure mediated drug delivery systems and their potential applications for the treatment of diseases. We focused on the challenges and bottlenecks to commercialization of nanomedicines. Results: Currently available conventional therapeutic devices require frequent drug administration due to the non-specific bio-distribution and rapid premature metabolism of free drug molecules. With the remarkable development of nanostructure devices during the last 2-3 decades, new drug delivery approaches based on nanotechnology have been receiving significant attention and gaining popularity. Researchers, both from the academia and industries are giving significant importance in the development of various nanostructure mediated drug delivery devices, as evident from numerous academic publications every year. Unfortunately, till date, few nanostructure mediated dosage forms have been commercialized and reached to the market. Current challenges associated with the manufacturing of such nanostructure based delivery systems are associated with their various physicochemical characteristics such as to balance the small particle size along with high drug loading, toxicity issues, and to obtain a stable nano drug delivery device. Conclusion: This review will help the formulation scientists to understand the critical strategies that are commonly used in the development of various nanostructure mediated drug delivery systems with a special emphasis on challenges which needs to be monitored and optimized during the product development to achieve a therapeutically active drug delivery system.

Certain mechanism like presence of highly complex structure i.e. blood brain barrier (BBB), P-glycoprotein (active efflux transporter) and certain enzymatic activity protect the brain in adverse conditions. These mechanisms especially BBB frustrate therapeutic interventions during the treatment. As a result most of the drug substances are fruitless in treating brain disorders, because they are not able to reach the brain in desired amount required for therapeutic activity. As a consequence, several invasive and non-invasive strategies are presently being used to increase the delivery of drugs across the BBB by opening it. However, opening the BBB by such strategies may allow the entry of certain undesirable substances to the brain and may cause the damage. There are several drugs (especially peptides and proteins) which cannot cross the BBB or produce the systemic side effects when given orally. Due to the potential problems, an attempt has been made to conquer the barrier issues in-vivo by using a noninvasive approach i.e. intranasal drug deliver using solid lipid nanoparticles (SLNs). It is an innovative, practically feasible and simple approach for delivery of certain categories of drug that cannot reach the brain due to above mentioned reasons. The drug administered through intranasal route bypasses the BBB and prevents the systemic exposure of drug and hence systemic side effects associated with drug molecules. This is due to the unique connection provided by olfactory and trigeminal nerves between the brain and external environment. SLNs are lipid nanoparticles made up of solid lipids, possessing exclusive benefits over other drug delivery carriers. The lipids used for the preparation of SLNs are usually biocompatible. They can be used as drug carrier to overcome the BBB when administered through nose. The article aims to discuss the various barriers to CNS drug delivery, strategies to overcome the BBB, anatomy and physiology of nose, SLNs & their characteristic parameters and applications of SLNs in brain delivery.

Background: We have designed and patented a novel nanocarrier system to specifically deliver IL-2 to tumor cells expressing the IL-2 receptor (IL-2R). In this work, we provide data of the physical characteristics of the system, such as size, complexity and viscosity, stability to light, pH and temperature, pharmacodynamic and pharmacokinetic parameters, as well as toxic and antitumor properties. The nanocarrier system consists of positively charged liposomes that present non-covalently bound IL-2 molecules on their external surface to facilitate recognition by IL-2R expressing cells. Methods: We used transmission electron microscopy and flow cytometry to evaluate physical characteristics of the system and immunodeppressed CBA mice for toxicological, pharmacodynamic and pharmacokinetic parameters. Results: Our results show that liposomes in our system have a unilamellar structure, small enough to be easily internalized by tumor cells, a viscosity similar to water, and are stable over a wide range of light, pH and temperature conditions, which provide them with convenient properties for pharmaceutical dosage forms, and storage stability. By using an animal model of immunodeppressed CBA mice induced to form tumors derived from cervical cancer human cells, we show that our liposomes are non-toxic even at very high doses of liposome bound IL-2 molecules, and that far lower doses are very effective in significantly reducing the tumor burden. Our system has the same antitumor effect than free IL-2, but in the absence of extremely high toxicity associated with this molecule when administrated systemically, and at a longer permanence in tissues. Conclusion: Our results shows that our system has low toxicity, long tissue permanence, and high antitumor activity, thus we propose the possibility that our IL-2 nanocarrier system could be useful for anti-cancer therapy when tumor cells express the IL-2R.

Background: Treatment by using magnetic nanoparticles is an emerging concept. Currently, magnetic nanoparticles (MNP) are being used for hyperthermia, targeting of drugs (active or passive), and for diagnostic purposes using nuclear magnetic resonance imaging. Objective: In the present study, imatinib-loaded chitosan magnetic nanoparticles were formulated by modified ionic gelation method. The purpose of the study was to explore the effect of the concentration of magnetite (X1) and the concentration of chitosan (X2) on the encapsulation of imatinib from magnetic nanoparticles using a central composite design. Methods: The formulated magnetic nanoparticles were characterized by laser light scattering, Fourier transform infrared spectroscopy, scanning electron microscope, and zeta potential measurement. Results: It was found that batch MNP-4 has the maximum encapsulation efficiency, loading capacity, and minimum particle size achieved for the optimized batch. Scanning Electron Microscopy (SEM) results confirmed a sphere-shaped or ellipsoidal morphology of the nanoparticles. A particle size analysis gives an average diameter of 188 nm. The encapsulation efficiency and drug loading were found to be (7.22 ± 0.13) and (5.16 ± 0.34) mg/100 mg, respectively, for the optimized batch. In-vitro drug release studies disclosed that 91.05% of the drug was released cumulatively. The magnetic characteristics were confirmed by a vibrating sample magnetometer. The saturation of magnetization was found to be 1.408 emu/g. VSM analysis confirmed that the as-prepared magnetic chitosan nanoparticles have a satisfactory magnetic receptivity for a prospective magnetic drug carrier for targeted delivery. The encapsulation efficiency was highest at the highest levels of chitosan and magnetite concentration. The encapsulation was lowest at the lowest level of the chitosan concentration. Conclusion: The magnetic and nano-effects due to the presence of magnetite and crosslinked chitosan are strong determining factors for the utilization of the prepared nanoparticles for various targeted applications. The model developed in the current study can be further utilized as response surface for the encapsulation efficiency of MNPs.

Background: Irbesarten antagonizes angiotensin II by blocking AT1 receptors in hypertension. Objective: To develop hydrophobically modified starch nanoparticles and to increase the dissolution and bioavailability of Irbesarten. Methods: The synthesis of palmitic acid grafted maize starch (PAgMS) using long chain fatty acid was performed by esterification. The formation of palmitic acid grafted maize starch (PAgMS) was confirmed by FTIR and NMR study. Particle size measurements, zeta potential, percentage drug entrapment efficiency were characterized to optimize formulations. Results: The particle size of formulation shows smaller particle size and high drug entrapment efficiency. All formulations showed negative zeta potential which results in better stabilization of the nanoparticles. The Scanning electron microscopy (SEM) results revealed that Irbesarten was present in amorphous state in the polymer. There was a significant enhancement of in vitro release (94.75%) of Irbesarten from PAgMS nanoparticles as compared to pure Irbesarten (20%) in 60 min. Irbesarten loaded palmitic acid grafted maize starch (PAgMS) nanoparticles showed significant increase (P<0.001) in relative bioavailability than marketed formulation. Conclusion: In conclusion, the prepared Irbesartan loaded palmitic acid grafted maize starch (PAgMS) nanoparticles showed remarkable increase in dissolution rate and hence bioavailability in rabbit.