Drug Delivery System

The use of medicines is an irreplaceable necessity in healthcare delivery. Application of advancing technology, especially the oral film techniques in pharmaceutical production has resulted in medicine availability in a trendy, readily acceptable and usable form, oral films. Although many literature abound on oral film delivery systems, there is paucity of work on recent incorporation of nanotechnology concepts and the potentials of this delivery system in improving medication adherence. Thus this work focuses on bridging this obvious gap. It reviews published works on the oral film technology, profiling recent advances in the nanoparticles incorporated into films, and necessary considerations in such formulations. It also explores oral films as a delivery system for improved adherence. Online search for articles on oral films production, marketed nanoparticle-based oral films, and the extensiveness of medication non-adherence was carried out using websites of researchgate, google search, film manufacturer's websites, google scholar and pubmed. Search terms used were 'marketed oral films', 'available medicines as oral films', 'nanotechnology in oral film production', 'oral film techniques', 'oral films manufacture + disease condition' and 'medicine adherence'. Articles were sorted on the basis of currency and practicality of information. The market space of oral film is growing steadily. Present use of oral film technology in delivering antipsychotics, antihistamines and analgesics is well received. Many drugs are currently incorporated into films in nano-sized forms to improve dissolution, bioavailability and effectiveness as revealed by the search. More can be achieved if this technology is extended to cover other classes of drugs such as antihypertensives, antiulcers and agents indicated for other chronic conditions. Fully exploring the unique features of the conventional oral films dosage forms and those embedded with nanoparticulate drug forms, therein lies the potentials to contribute to significant improvement in medication adherence even in chronic conditions.

In this paper, we present design of a transdermal drug delivery system for treatment of cardiovascular or hemodynamic disorders such as hypertension. The system comprises of integrated control electronics and microelectromechanical system devices such as micropump, micro blood pressure sensor and microneedle array. The objective is to overcome the limitations of oral therapy such as variable absorption profile and the need for frequent dosing, by fabricating a safe, reliable and cost effective transdermal drug delivery system to dispense various pharmacological agents through the skin for treatment of hemodynamic dysfunction such as hypertension. Moreover, design optimization of a piezoelectrically actuated valveless micropump is presented for the drug delivery system. Because of the complexity in analysis of piezoelectric micropump, which involves structural and fluid field couplings in a complicated geometrical arrangement, finite element (FE) numerical simulation rather than an analytical system has been used. The behavior of the piezoelectric actuator with biocompatible polydimethylsiloxane membrane is first studied by conducting piezoelectric analysis. Then the performance of the valveless micropump is analyzed by building a three dimensional electric-solid-fluid model of the micropump. The effect of geometrical dimensions on micropump characteristics and efficiency of nozzle/diffuser elements of a valveless micropump is investigated in the transient analysis using multiple code coupling method. The deformation results of the membrane using multifield code coupling analysis are in good agreement with analytical as well as results of single code coupling analysis of a piezoelectric micropump. The analysis predicts that to enhance the performance of the micropump, diffuser geometrical dimensions such as diffuser length, diffuser neck width and diffuser angle need to be optimized. Micropump flow rate is not strongly affected at low excitation frequencies from 10 to 200 Hz. The excitation voltage is the more dominant factor that affects the flow rate of the micropump as compared with the excitation frequency. However, at extremely high excitation frequencies beyond 8,000 Hz, the flow rate drops as the membrane exhibits multiple bending peaks which is not desirable for fluid flow. Following the extensive numerical analysis, actual fabrication and performance characterization of the micropump is presented. The performance of the micropump is characterized in terms of piezoelectric actuator deflection and micropump flow rate at different operational parameters. The set of multifield simulations and experimental measurement of deflection and flow rate at varying voltage and excitation frequency is a significant advance in the study of the electric-solid-fluid coupled field effects as it allows transient, three dimensional piezoelectric and fluid analysis of the micropump thereby facilitating a more realistic multifield analysis. The results of the present study will also help to conduct relevant strength duration tests of integrated drug delivery device with micropump and microneedle array in future.

A novel drug-delivery system was developed by loading the anticancer drug, mitomycin C (MC) into an oil/water system with the aim of investigation by electrochemical sensing the interaction between the drug and DNA in microemulsion phase. The physical and physicochemical properties (droplet size, pH, viscosity, conductivity and refractive index) of this microemulsion were examined. The electrochemical detection of the interaction between MC and double-stranded DNA (dsDNA) in microemulsion phase was performed by using differential pulse voltammetry (DPV) in combination with a disposable sensor, pencil graphite electrode (PGE). The magnitude of guanine oxidation signal was monitored before and after interaction between MC and dsDNA. The effect of different experimental parameters, such as MC concentration, MC interaction time with dsDNA, and dsDNA concentration were also studied to find the optimum analytical performance based on electrochemical detection of this interaction in microe...

Over the past several years, great advances have been made on development of novel drug delivery systems (NDDS) for plant actives and extracts. The variety of novel herbal formulations like polymeric nanoparticles, nanocapsules, liposomes, phytosomes, nanoemulsions, microsphere, transferosomes, and ethosomes has been reported using bioactive and plant extracts. The novel formulations are reported to have remarkable advantages over conventional formulations of plant actives and extracts which include enhancement of solubility, bioavailability, protection from toxicity, enhancement of pharmacological activity, enhancement of stability, improved tissue macrophages distribution, sustained delivery, and protection from physical and chemical degradation. The present review highlights the current status of the development of novel herbal formulations and summarizes their method of preparation, type of active ingredients, size, entrapment efficiency, route of administration, biological activity and applications of novel formulations.The novel formulations reported to have remarkable advantages over conventional formulations of plant actives and extracts.

Ketorolac tromethamine is a non-steroidal anti-inflammatory drug that has two major problems when administered orally; it has
severe gastrointestinal side effects as bleeding, peptic ulcer, perforation. Second, it has short half-life (4hr) so require frequent
administration. The aim of this study was to overcome these two problems through preparation of this drug as topical hydrogel.
Hydroxypropyl, hydroxylpropylmethyl, and sodiumcarboxymethyl were the three cellulosic polymers used as gelling agents, the
influence of type and concentration of them on the release of ketorolac was investigated. Oleic acid, tween 80, carveol, and
isopropyl alcohol were used as penetration enhancers, and effect of these enhancers on diffusion of ketorolac across semipermeable
membrane was tested. The optimized formula was evaluated for its anti- inflammatory action on carragenan induced rat
paw edema model. Results revealed that the hydrogel formulations exhibited high drug release especially at low polymer
concentration and the release was follow diffusion controlled mechanism. All enhancers showed enhancement in ketorolac
penetration specially the optimized formula contain Ketorolac 2%, HPMC 1%, and 0.5% Tween 80, which exhibited improved antiinflammatory
activity. So it can be concluded that topical hydrogel enhanced permeation of ketorolac and given an effective antiinflammatory
activity, with avoidance of GIT adverse effect.

Starch nanoparticles were prepared from native potato starch using acid hydrolysis and precipitation methods. The acid hydrolysis method yielded high relative crystallinity of starch nanoparticles (SNP-H), while ethanol precipitation method resulted in nanoparticles (SNP-P) with low crystallinity, which shows a broad peak in diffractogram. SNP-P has higher drug loading capacity than SNP-H. The modification of nanoparticles using CTAB resulted in the highest drug loading compared to SDS and Tween 20. A sustained release mechanism at pH 5.8 and 7.4 was observed for SNP-H. Anionic surfactant modified SNP shows the burst release in the initial time of drug release. The cumulative release is lower at pH 5.8 than pH 7.4. The simple sigmoidal function and Higuchi model were used to represent the kinetic release profile of Paclitaxel from starch nanoparticles. Cytotox-icity assay of the original nanoparticles showed good biocompatibility of nanoparticles with 7F2 cells.

Propolis is a natural product with a plethora of biological effects, utilized by traditional medicine since antiquity. However, its application as a pharmaceutical is hindered by its variable composition and difficult standardization. CAPE has been shown to be a major component of propolis, with a large contribution to its pharmacological effects, among which the anti-inflammatory, antioxidant and antineoplastic have been attracting most attention. The current review article aims to present the cornerstone pharmacological studies of CAPE throughout the years, following its discovery, which confirmed its primary importance among propolis constituents and opened the path to its intensive research as a potential pharmaceutical. We present the diversity of drug delivery systems of CAPE, which have been developed to improve its efficacy in in vitro and in vivo disease models and discuss their primary promises and weaknesses. The increased interest in recent years over more practical approaches of CAPE research such as its pharmaceutical formulation comes to show that it has a potential to become commercialized as a pharmaceutical.

The combination of an efficient encapsulation method of small water-soluble substances with a stimuli-responsive release of defined quantity remains a challenging task. A novel drug delivery system (DDS) representing a free-standing PLLA microchamber arrays film and its application as the cover for implantable endovascular stent are reported in this work. The proposed DDS preparation method is consisting of a patterned polydimethylsiloxane (PDMS)-stamp dip-coated into a polymer solution followed by drug loading and sealing it by polymer pre-coated substrate. It was shown that using 1 wt.% PLLA solution is optimal for obtaining microchamber arrays with an individual cargo capacity of 2.88×10-9µg, which was successfully loaded by model drug substance Rhodamine B. Rhodamine B was completely released in vitro during 13 days in PBS at 37 °C by diffusion.  It was demonstrated that low-frequency ultrasound (LFUS, 20 kHz) allows triggering RhB release due to microchamber damage and detachment of individual PLLA microchambers over time. LFUS exposure time up to 25 s led to RhB release of up to 8.4×10-4µg (approximately 55%) from microchambers located on the flat substrate; up to 5.2×10-4µg from microchambers located on the stent with using a simplified vessel model. Furthermore, the free-standing printed PLLA microchamber arrays were demonstrated to be applied as endovascular stent cover that can be used for complementary pharmacological effect, for example, triggered local delivery of anticoagulants.

Reactive oxygen species (ROS) (H2O2, OCl−, •OH, O2−) are a family of reactive molecules that are generated intracellularly and are engaged in many
biological processes. In physiological concentrations, ROS act as signaling
molecules to a number of metabolic pathways; however, in excess they can
be harmful to living organisms. Overproduction of ROS has been related
to many pathophysiological conditions and a number of studies have been
reported in elucidating their mechanism in these conditions. With the aim of
harnessing this role, a number of imaging tools and therapeutic compounds
have been developed. Here these imaging and therapeutic tools are reviewed
and particularly those structures with ROS-sensitivity based on their biomedical applications and their functional groups. There is also a brief discussion
about the method of preparation as well as the mechanism of action.

Bioerodible polymers used in controlled drug delivery systems, such as poly(lactic-co-glycolic acid) (PLGA) undergo radiolytic degradation during γ-irradiation. In spite of the considerable practical importance, yet only little knowledge is available on the consequences of this sterilization method on the resulting drug release patterns in a quantitative way. The major objectives of the present study were: (i) to monitor the

Aims: The abstract of the current study was to formulate amikacin sulfate in a liposomal formulatiom for enhancing its efficacy and safety.
Place and Duration of Study: Pharmaceutical Technology Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Cairo, Egypt, between 2010-2013.
Methodology: Amikacin sulfate liposomes were prepared by the vortex dispersion method using dipalmitoyl phosphatidyl choline (DPPC), cholesterol (CHOL) and charge inducing agent (CIA).
Dicetyl phosphate (DCP) and Stearyl amine (SA) were added as the negative and positive charge inducing agents respectively. Characterization of the prepared amikacin sulphate liposomes was performed. In-vitro release of selected formulations was estimated. A stability study for 45 days was performed. Investigation of the optimum dose for sterilization of amikacin sulfate liposomes was carried out. Selected amikacin sulfate liposomal formulations activities were evaluated against
Escherichia coli infection in mice and compared to the free drug.
Results: The entrapment efficiencies ranged from 43.6±1.81 to 62.5±2.57%, the vesicles are well identified and present in a nearly perfect sphere like shape ranging in size from 54.3±11 to
362.1±56 nm and the polydospersity index values of all liposomal formulations were < 0.3. DSC of different liposomal formulations shows a change in transition temperature of the main phospholipids. In-vitro release profiles revealed biphasic release of the drug from liposomes. Physical stability performed at 2-8ºC for 45 days revealed low leakage of drug from all liposomal formulations investigated. Sterilization using gamma radiations revealed that a dose of 25 KGy was the optimum sterilization dose. The results also revealed less number of colonies forming units (cfu/ml) in the case of amikacin sulfate liposomes than the unentrapped drug.
Conclusion: It can be fulfilled from this work that amikacin sulfate liposomes represent promising carrier for delivery of amikacin offering good physical stability, high entrapment effeciencies and controlled drug release.

The preparation of responsive superparamagnetic iron oxide (SPIO) nanoparticles (NPs), able to carry the anticancer drug doxorubicin (DOX) and to release it in physiological media at the physiological temperature, is one of the major challenges in nanomedicine. In this work, two families of NPs were synthesized. The first one consists of superparamagnetic Fe 3 O 4 NPs functionalized via covalent grafting by a biocompatible responsive copolymer based on 2-(2-methoxy)ethyl methacrylate (MEO 2 MA) and oligo(ethylene glycol) methacrylate (OEGMA). The second one consists of the same core/shell NPs but folic acid, a biological cancer targeting molecule, was grafted at the polymer chain end. The core/shell NPs were fully characterized by the combination of spectroscopic and microscopic techniques. The influence of the polymer chain structure in water and in physiological media was studied. We demonstrate that the magnetic properties of the NPs were only influenced by the amount of the graf...

A primary object of using mucoadhesive formulations orally would
achieve a substantial increase in the length of stay of the drug in GI
tract  stability  problem  in  the  intestinal  fluid  can  be  improved.
Mucoadhesive  microsphere  carrier  systems  were  made  from  the
biodegradable polymers in sustained drug delivery. The objective of
the  present  study  is  related  to  the  preparation  and  evaluation  of
mucoadhesive  microspheres  of  simvastatin  by  using  different
polymers like Sodium alginate, HPMC K100M, Sodium CMC, Ethyl
cellulose, Methyl cellulose, Guar gum, Xanthan gum and Carbopol
940 in different ratios by the Ionic deletion method. The prepared
batches of mucoadhesive microspheres of simvastatin were evaluated
for  the  flow  properties;  drug  content,  entrapment  efficiency,  and
Percent mucoadhesive property, in vitro dissolution studies of all 12
formulations were performed. From the all batches F10 (Drug: Sod.
Alginate: Methyl cellulose 1:2:1) batch is considered to be the most
promising formulation batch because among all the batches it shows
better  extent  of  drug  release  97.11%  (8hrs),  good  entrapment
efficiency  (78%),  and  in  vitro  wash-off  test  shows  the  good
mucoadhesive property. Simvastatin release from alginate – Methyl
cellulose (F10)  was  slow and extended over a period of 8 hrs and
these microspheres were found suitable for the oral controlled release
formulation.

One of the most exciting innovations of the 21st century is nanotechnology. Nanoscience is a combination of physics, materials science, and biology that deals with atomic and molecular scale. The top-down approach includes the breakdown into nanosized structures or particles of bulk material. The 'bottom-up' is the alternative approach, which has the opportunity to produce less waste and also more economically. By using natural asbestos nanofibers more than 4,500 years ago, humans have already manipulated ceramic matrix reinforcement. The synthesis of a colloidal Au nanoparticle solution was reported by Michael Faraday in 1857, which was the first scientific explanation to report nanoparticle preparation and initiated the history of nanomaterials in the scientific arena. Carbon-based materials became the foundation of almost every field of science and engineering after the discovery of' graphene. Important advancements in the field of nano-oncology have also been made by enhancing the effectiveness of conventional chemotherapy drugs for a plethora of aggressive human cancers Keywords: Nanotechnology, top-bottom approach, drug delivery I. INTRODUCTION A Greek prefix meaning 'dwarf' or anything very small is referred to as the prefix 'nano' and represents one thousand millionths of a meter (10-9 m). We should differentiate nanoscience and nanotechnology from each other. Nanoscience is the analysis of structures and molecules on nanometer scales ranging from 1 to 100 nm, and the technology that uses it is called nanotechnology [1] in practical applications such as devices etc. The evolution of nanoscience can be traced back to the time in the 5th century B.C. of the Greeks and Democritus, when scientists considered the question of whether matter is continuous, and thus indefinitely divisible into smaller parts, or made of small, indivisible and indestructible particles, now called atoms by scientists. One of the most exciting innovations of the 21 st century is nanotechnology. It is the ability to transform the theory of nanoscience to useful applications across the nanometer scale of observing, measuring, manipulating, assembling, managing and manufacturing matter. "In the United States, the National Nanotechnology Initiative (NNI) describes nanotechnology as a nanoscale science, engineering and technology (1 to 100 nm) where specific phenomena allow new applications in a broad range of fields, from chemistry, physics and biology to medicine, engineering and electronics"[2]. We should differentiate nanoscience and nanotechnology from each other. Nanoscience is a combination of physics, materials science, and biology that deals with atomic and molecular scale material manipulation, while nanotechnology is the ability to measure, manipulate, assemble, monitor, and generate matter on a nanometer scale. There are several reports available that have given the history of nanoscience and technology, but no study is available that summarizes the revolutionary events of nanoscience and technology from the beginning of that period. It is therefore important to summarize the key events in nanoscience and technology in order to fully understand their progress in this area.

Bile salts containing vesicles (bilosomes) represent a portentous vesicular carrier that showed prosperous
results in delivering active moieties in the gastrointestinal tract (GIT). In this study, bilosomes were
exploited to deliver sulfated polysaccharide–protein complexes of Enteromorpha intestinalis (EHEM) and
enhance its activity against hepatocellular carcinoma as well as resist harsh GIT conditions. Bilosomes were
prepared using the sodium salt of three different bile acids (cholic, deoxycholic, taurodeoxycholic) and two
different nonionic surfactants (Span 40 and 65). The effects of experimental variables were thoroughly
studied to obtain an optimum formulation loading EHEM. The selected formulation (EH-Bilo-2) prepared
with sodium cholate and Span 65 displayed nano-sized (181.1 ± 16.80 nm) spherical vesicles with reasonable
entrapment efficiency (71.60 ± 0.25%) and controlled release properties; and thus was investigated as
anti-hepatocarcinogenic candidate for in vivo studies. Treatment of hepatocellular carcinoma (HCC) bearing
rats with EH-Bilo-2 experienced significant decrease in serum a-fetoprotein, endoglin, lipocalin-2, and heat
shock protein 70 levels vs. the untreated counterparts. Furthermore, the photomicrographs of their liver
tissue sections showed focal area of degenerated pleomorphic hepatocytes with fine fibrosis originating
from the portal area. Thus, the optimized bilosomal formulation is a promising delegate for tackling hepatocellular
carcinoma owing to its powerful anti-cancer and anti-angiogenic activity.