Pharmaceutical Drug Carriers Research Articles

Poloxamer-Based Hydrogel as Drug Delivery System: How Polymeric Excipients Influence the Chemical-Physical Properties.

Thermogelling amphiphilic block copolymers have been widely investigated in the development of pharmaceutical drug carriers. In particular, thermosensitive gels based on poloxamer 407 (P407) have great potential for periodontal disease treatment, thanks to their ability to be liquid at room temperature and become viscous gels at body temperature. However, some problems, related to short in situ residence time, reduce their feasible clinical use. Thus, in order to improve the effective applicability of these materials, we studied how P407 thermogels are affected by the pH and by the inclusion of different hydrophilic polymers, used as excipients for increasing the gel stiffness. For this scope, a complete chemical-physical characterization of the synthesized gels is provided, in terms of determination of sol-gel transition temperature, viscosity and erosion degree. The data are correlated according to a statistical multivariate approach based on Principal Component Analysis and their mucoadhesion properties are also tested by Tapping mode-Atomic Force Microscopy (TM-AFM) imaging. Finally, we studied how the different P407 formulations are able to influence the release pathway of two antibacterial drugs (i.e., chlorhexidine digluconate and doxycycline hyclate) largely used in oral diseases.

Mucosal Applications of Poloxamer 407-Based Hydrogels: An Overview.

Poloxamer 407, also known by the trademark Pluronic® F127, is a water-soluble, non-ionic triblock copolymer that is made up of a hydrophobic residue of polyoxypropylene (POP) between the two hydrophilic units of polyoxyethylene (POE). Poloxamer 407-based hydrogels exhibit an interesting reversible thermal characteristic. That is, they are liquid at room temperature, but they assume a gel form when administered at body temperature, which makes them attractive candidates as pharmaceutical drug carriers. These systems have been widely investigated in the development of mucoadhesive formulations because they do not irritate the mucosal membranes. Based on these mucoadhesive properties, a simple administration into a specific compartment should maintain the required drug concentration in situ for a prolonged period of time, decreasing the necessary dosages and side effects. Their main limitations are their modest mechanical strength and, notwithstanding their bioadhesive properties, their tendency to succumb to rapid elimination in physiological media. Various technological approaches have been investigated in the attempt to modulate these properties. This review focuses on the application of poloxamer 407-based hydrogels for mucosal drug delivery with particular attention being paid to the latest published works.

Current trends and concepts in the design and development of nanogel carrier systems

Nanotechnology, a relatively novel technique, has much potential in smart drug delivery. Development of novel nanosized particulate drug delivery systems (DDS) may help in disease prevention, diagnosis, and treatment of many of the important diseases. Nanogels have particle sizes in the 0–100 nm range, and the three-dimensional network is maintained by varying the solvent quality. This review article describes concisely the current trends and concepts involved in the design and development of nanogel DDS. This review also explores the various approaches of drug loading, release mechanisms, characterization, and biomedical applications. Optimized nanogel systems can be developed on the basis of the site of action and pattern of drug release desired for improved therapeutic benefits. This can be achieved by using the appropriate method of preparation (physical or chemical) and drug loading mechanism by modifying the geometry and surface of the nanogels. The properties of nanogels are dependent on the constituent materials/components (synthetic or natural) and on external stimuli (pH, temperature, ionic strength or incorporation of hydrophilic residues) in the case of stimuli-sensitive nanogels. Due to the high stability, biodegradability, biocompatibility, large surface area, and minimal resources required for manufacture of nanogels, their applications (such as in oral, pulmonary, nasal, ocular, and topical routes) have gained special attention in the development of pharmaceutical drug carriers.

Conformational, Dynamical. and Tensional Study of Tethered Bilayer Lipid Membranes in Coarse-Grained Molecular Simulations

Tethered bilayer lipid membranes (tBLMs) have attracted great interest recently due to their crucial roles in elucidating fundamental membrane characteristics and the implications in biochemical sensors and pharmaceutical drug carriers. Nevertheless, they have not yet been investigated computationally on the molecular scale. Here, we study tBLMs consisting of DOPCs (1,2-dioleoyl-sn-glycero-3-phosphocholine) as free lipids and pegylated DOPCs (on phosphate group) as tethers in water by a variation of the MARTINI model. By varying grafting densities and tether lengths, distinct conformational changes from planar to undulated bilayers are observed. Lateral diffusivities and lateral pressure profiles show that the dynamical and tensional states are specific to the system configurations. These results suggest that the conformations, fluidity, and elasticity of the tBLMs can be tuned and manipulated to conform to various requirements in theoretical investigations and technological applications.

Theoretical and experimental study of the tetracain/β-cyclodextrin inclusion complex

The local anaesthetic Tetracain has previously been found to block, induce or potentiate Ca2+ release from the sarcoplasmic reticulum of skeletal muscle. Cyclodextrins (CD) are complexing agents that have been successfully used as pharmaceutical drug carriers, to improve the bioavailability of medicines. The aim of this work is to investigate the inclusion process of the local anesthetic Tetracain with the beta-cyclodextrin at the Hartree–Fock level of theory calculations with a 6-31G (d) basis set, and to evaluate stabilization upon the formation of the inclusion compounds for 1:1 association. The inclusion process pathways are described and the most stable structures of the different complexes are sought through a global potential energy scan. The data suggest that the most stable structure for the 1:1 stoichiometry between the Tetracain and the β-CD is obtained when the inclusion complex formed by Tetracain from the tertiary amine group, entering into the cavity of β-CD from its narrow side (i.e. the primary 6-CH2OH hydroxyl group). Structure–activity relationship is discussed in terms of different molecular descriptors and experimental Raman spectroscopy measurements at different mole fraction for the inclusion complexes analyzed and compared with our theoretical constructed Raman spectra.

Nanoparticles: Crossing barriers and membrane interactions

In recent years, the field of nanotechnology has progressed at an exponential pace and is now at the forefront of medical research. Future nanomedicine (primarily the field of cancer nanotechnology) is projected to have an enormous impact on both diagnostics and treatment modalities to improve human health. Therefore, research and development of engineered multifunctional nanoparticles as imaging tools and pharmaceutical drug carriers is an area of current interest. The field of nanomedicine embraces a number of outstanding questions, critical for successful applications of nanoparticles in disease identification and cure. These include: (a) Technological developments to produce monodisperse drug-loaded nanocarriers, (b) biological factors affecting accumulation of nanocarriers to the diseased tissues including skin; (c) intracellular localization of nanoparticles via receptor-mediated targeting; (d) exploitation of the microenvironment of the tumour tissue for selective targeting of nanoparticles; (e) an understanding of molecular interactions between nanoparticles, biological membranes, intracellular organelles, preferred drug transport mechanisms; and finally (e) strategies for localized drug release intracellularly or in the vicinity of the tumours. It is our intention to address some of these issues in this special issue. Articles from experts in their respective research disciplines in nanomedicine are included to provide a broad overview of the current status of nanoparticle research. The papers present the latest information on the fabrication of nanoparticles, issues related to targeting, effect of route of administration, nano-imaging tools, and on-demand drug release. Each of these research fields provide excellent opportunities for cancer treatment, yet face limitations. The primary modes of nanoparticle delivery include intravenous, topical and oral administration. In either case, the ability of nanoparticles to cross barriers, such as the skin (topical delivery route) or GI tract (oral administration) or blood brain barrier (BBB) is a prerequisite for their success. It is important to understand the molecular mechanisms of nanoparticle-membrane interactions during multiple steps. Therefore the studies aimed at examining the barriers that are posed by various membranes (such as skin, cellular membranes or GI tract) deserve a closer look. In addition, coating of nanoparticles to target specific ligands has been demonstrated to improve intracellular accumulation. Therefore issues related with passive vs. active targeting of nanoparticles will bear their own merits and reservations. Saha and colleagues describe the strategies of fabrication for nanoparticulate drug delivery systems, and critical issues related to production of clinically relevant nanoparticles. The authors further discuss the factors that govern in vivo distribution of the nanoparticles. Along similar lines, Torchilin and Sawant describe another interesting platform, ‘phospholipid micelles’ as versatile pharmaceutical nanocarriers. Here, the authors also address an important issue of in vivo stability by using polyethyleneglycol phosphatidylethanolamine (PEG-PE)-based micellar drug delivery systems. It is worth mentioning that the nanoassemblies bearing pegylated molecules (such as liposomes) have proven to be extremely successful for in vivo drug delivery. Two papers are focused on drug delivery aspects resulting from passive accumulation. Sachdeva, Desai and colleagues discuss the nanoparticle interactions with the skin (first barrier). This article also presents the role of cell penetrating peptides (CPP) in modulating trans-dermal drug delivery. Amiji and colleagues present another clinically viable nanoparticulate assembly for drug delivery based on natural oils

Modeling and characterization of drug release from glutinous rice starch based hydrogel beads for controlled drug delivery

Purpose: To identify the potential of Assam Bora rice in modulation of drug release from the formulated matrix devices and demonstrate its utility in pharmaceutical drug carrier systems. Methods: The hydrogel microbeads were prepared by an industrially feasible conventional ionotropic gelation method using the blends of pregelatinized Bora rice along with sodium alginate as mucoadhesive backbone. The potential of proposed natural polymer in modulation of drug release from the formulated microbeads was investigated through in vitro dissolution test conducted as per SUPAC-MR guidelines provided by FDA. Data obtained from in vitro release studies were fitted to various kinetic equations to find out the kinetics and mechanism of drug release from fabricated microbeads. Results: The microbeads were almost spherical, discreet and free flowing in a size range of about 0.726±0.008 mm to 1.16±0.009 mm. The different formulations had variable correlation with the different kinetic models under the different release environments. Conclusion: Assam Bora can be a promising option for mucoadhesive controlled drug delivery systems as natural substance. Keywords: Drug delivery, Bora rice starch, Release kinetics, Natural polymer.

Silica xerogels as pharmaceutical drug carriers

This review focuses on silica xerogels obtained by the sol-gel method and their application as drug delivery systems. SiO2 xerogels are potential biomaterials to be used as matrix materials for the extended and controlled release of different kinds of biologically active agents administered by various routes. The article includes some representative examples that describe the encapsulation of bioactive molecules and model compounds inside a silica matrix produced by the conventional sol-gel method or by ultrasound hydrolysis. The drug release rate from xerogels could be modified by adjusting several parameters, such as the type of precursor, the concentration of the catalyst and drying temperature. In vitro and in vivo studies have shown the efficacy and biodegradability of these composites. The potential application of silica xerogels as drug carrier systems is critically analyzed and discussed.

Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic.

In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical drug carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nanoemulsions, dendrimers, nano-gold, liposomes, drug-carrier conjugates, antibody-drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid carriers will be presented. We conclude with a few examples of clinically successful formulations of currently available lipid-based nanoparticles.

Investigation of tetracaine complexation with beta-cyclodextrins and p-sulphonic acid calix[6]arenes by nOe and PGSE NMR

Cyclodextrins (CD) and calixarenes are complexing agents that have been successfully used as pharmaceutical drug carriers, to improve the bioavailability of medicines. The aim of this work was to investigate the complexation of the local anesthetic tetracaine 1 with β-cyclodextrin 2, as well as with p-sulphonic acid calix[6]arene 3. 1H NMR experiments were carried out in D2O, i.e., with the charged tetracaine species 1. HR-DOSY 1H NMR allowed determination of the fraction of complexed population (%p bound = 55% and 70%) and the apparent association constants (K a = 1358 and 3889 M−1), respectively, for 1/2 and 1/3. These results confirm that a strong association takes place between 1 and 2, while the 1/3 complex is even more stable, due to the negatively charged sulphonic groups of 3. Studies conducted at pH 10 revealed that the association of the uncharged form of 1 with 3 is considerably weaker, while that with 2 increased significantly (K a = 6597 M−1), protecting the anesthetic against alkaline hydrolysis. 1H-ROESY 1D NMR experiments allowed determination of the host-guest relative positions, revealing that the proposed topologies for the 1/2 and 1/3 complexes were quite different. The complexation of 1 with either 2 or 3 is being investigated in view of its potential use in new therapeutic formulations, designed to increase the bioavailability and/or to decrease the systemic toxicity of tetracaine, in anesthesia procedures.

Chitosan: A Unique Polysaccharide for Drug Delivery

The aim of this review is to give an insight into the many potential applications of chitosan as a pharmaceutical drug carrier. The first part of this review concerns the principal uses of chitosan as an excipient in oral formulations (particularly as a direct tableting agent) and as a vehicle for parenteral drug delivery devices. The use of chitosan to manufacture sustained-release systems deliverable by other routes (nasal, ophthalmic, transdermal, and implantable devices) is discussed in the second part.

Selective liver targeting of antivirals by recombinant chylomicrons — a new therapeutic approach to hepatitis B

Hepatitis B virus (HBV) infection is the world's most important chronic virus infection. No safe and effective treatment is available at present, and clinical exploration of promising antiviral agents, such as nucleoside analogues is hampered because of significant side-effects due to their aspecific body distribution. We are exploring the possibility of the selective delivery of antiviral active drugs to liver parenchymal cells, the main site of infection and replication of HBV. Chylomicrons, which transport dietary lipids into the liver via apolipoprotein E-specific receptors, could serve as drug carriers. However, their endogenous nature hampers their application as pharmaceutical drug carriers. We report here that incorporation of a derivative of the nucleoside analogue iododeoxyuridine into recombinant chylomicrons leads to selective targeting to liver parenchymal cells. Potentially effective intracellular drug concentrations of 700 nM can be achieved, and we therefore anticipate that these drug carrier complexes represent a conceptual advance in the development of an effective and safe therapy for hepatitis B.