Controlled Release Drug Delivery Research Articles

Time-of-flight secondary ion mass spectrometry analyses of vancomycin.

As an antibiotic that prevents and treats infections caused by Gram-positive bacteria such as Staphylococcus aureus, vancomycin incorporated in a biodegradable polymer poly(lactide-co-glycolide) provides opportunities to construct controlled-release drug delivery systems. Developments associated with this promising system have been largely concentrated on areas of drug delivery kinetics and biodegradability. In order to provide surface analytical approaches to this important system, the authors demonstrate applicability of time-of-flight secondary ion mass spectrometry (TOF-SIMS) in three-dimensional molecular imaging for a model system consisting of alternating layers of ploy(lactide-co-glycolide) and vancomycin. TOF-SIMS imaging clarified that the two chemicals can undergo phase separation when dimethyl sulfoxide is used as the solvent. The authors identified two diagnostic ions that are abundant and structural moieties of vancomycin. The results on TOF-SIMS imaging and depth profiling vancomycin provide useful information for further applications of TOF-SIMS in the development of antibiotic drug delivery systems involving the use of vancomycin.

Chitosan nanoparticles/cellulose nanocrystals nanocomposites as a carrier system for the controlled release of repaglinide

The aim of the present work was to study the use of cellulose nanocrystals (CNC) and chitosan nanoparticles (CHNP) for developing controlled-release drug delivery system of the anti-hyperglycemic drug Repaglinide (RPG). CNC was isolated from palm fruit stalks by sulfuric acid hydrolysis; the dimensions of the isolated nanocrystals were 86–237 nm in length and 5–7 nm in width. Simple and economic method was used for the fabrication of controlled release drug delivery system from CNC and CHNP loaded with RPG drug via ionic gelation of chitosan in the presence of CNC and RPG. The prepared systems showed high drug encapsulation efficiency of about ~98%. Chemical modification of CNC by oxidation to introduce carboxylic groups on their surface (OXCNC) was also carried out for further controlling of RPG release. Particles size analysis showed that the average size of CHNP was about 197 nm while CHNP/CNC/RPG or CHNP/OXCNC/RPG nanoparticles showed average size of 215–310 nm. Compatibility studies by Fourier transform infrared (FTIR) spectroscopy showed no chemical reaction between RPG and the system's components used. By studying the drug release kinetic, all the prepared RPG formulations followed Higuchi model, indicating that the drug released by diffusion through the nanoparticles polymeric matrix.

Oral Controlled Drug Delivery System-A Review

The new generation of oral controlled release drug delivery system technologies brings valuable benefits to patients. Oral route is the most convenient and commonly route of drug delivery. Oral controlled release formulations are designed to deliver a drug at a pre determined rate by achieving a constant drug level for a specified period of time with lower side effects. Controlled release drug delivery have become a significant priority worldwide, it may be possible to achieve rapid absorption of drug and increased bio availability, reduced toxicity and improved patient compliance. This article mainly focuses the requirement of controlled drug delivery system, their advantages, disadvantages, formulation, various methods and use of controlled release system.

A Comprehensive Note on Gastro-Retentive Dosage Forms

Controlled release drug delivery system has achieved greater importance in the field of pharmaceutical sciences to provide therapeutic advantages over the conventional drug delivery system. Nowadays, the gastrointestinal controlled drug delivery systemis more prominent than the controlled release system because these can govern the release rate of therapeutically active drug for a sustained period. A Gastro retentive dosage form improves the therapy by prolonging the gastric residence time of the drugs. Prolonged gastric retention improvesbioavailability, reduces drug waste and improves solubility for drugs that are less soluble in a high pH environment. In this review, we have discussed various systems associated with gastro retentive drug delivery with their effective mode of action. Also, the approaches and factors to increase the gastric retention time have also been discussed. This drug delivery system has potential to overcome the limitations of the conventional system. The present study is performed for the motivation of the graduates towards publication and research. Hence, we have encouraged the graduates to prepare an informative article on the present subject.

A brief review on recent advances of extended release technology employed to design the oral dosage forms

The benefits offered by modified release systems include reduced dosing frequency with improved patient compliance, better and more uniform clinical effects with lower incidence of side effects and possible enhanced bioavailability. Characteristics of a modified release system as stated by USP is “The drug release characteristics of time, course and / or location are chosen to accomplish therapeutic or convenience objectives not offered by conventional dosage forms” [1]. This includes technologies that modify the site of drug delivery. Extended release dosage forms extend the life of a drug so that dosage regiment shifts from 3 times a day dosing just once or twice a day. The successful formulation of a modified release device requires a comprehensive understanding of the mechanism of drug release from the macroscopic effects of size, shape and structure through to chemistry and molecular interaction. Multiparticulate dosage forms shown to be less prone to food effects than monolithic and is often the preferred formulation for extended and / or delayed release. Extended release drug formulation is conventionally produced as compressed tablets by hydrogel tablet technology. To produce these extended release tablet dosage forms, active ingredient is conventionally compounded with cellulose ethers like methylcellulose, ethyl cellulose or hydroxyl propyl methylcellulose with or without excipients and the resulting mixture is pressed into tablets. When the tablets are orally administered, cellulose ethers in the tablet swell upon hydration from moisture in the digestive system, thereby limiting exposure of active ingredient to moisture. As the cellulose ethers are gradually leached away by moisture, water more deeply penetrates the gel matrix and the active ingredient slowly dissolves and diffuses through the gel, making it available for absorption by the body. An appropriately designed controlled release drug delivery system can be a major advance towards solving problems concerning the targeting of a drug to specific organ or tissue and controlling the rate of drug delivery to the target sites. The development of the oral controlled release system has been a challenge to formulation scientists due to their inability to restrain and localize the system at targeted areas of the gastro intestinal tract. Matrix type drug delivery systems as carriers for the active ingredients are interesting and promising option in developing an oral controlled release system. Tablets are the preferred dosage form for many drugs and are still the most widely used formulations for both new and existing modified released products.

Ultrasound-mediated cavitation-enhanced extravasation of mesoporous silica nanoparticles for controlled-release drug delivery

Mesoporous silica nanoparticles have been reported as suitable drug carriers, but their successful delivery to target tissues following systemic administration remains a challenge. In the present work, ultrasound-induced inertial cavitation was evaluated as a mechanism to promote their extravasation in a flow-through tissue-mimicking agarose phantom. Two different ultrasound frequencies, 0.5 or 1.6 MHz, with pressures in the range 0.5–4 MPa were used to drive cavitation activity which was detected in real time. The optimal ultrasound conditions identified were employed to deliver dye-loaded nanoparticles as a model for drug-loaded nanocarriers, with the level of extravasation evaluated by fluorescence microscopy. The same nanoparticles were then co-injected with submicrometric polymeric cavitation nuclei as a means to promote cavitation activity and decrease the required in-situ acoustic pressure required to attain extravasation. The overall cavitation energy and penetration of the combination was compared to mesoporous silica nanoparticles alone. The results of the present work suggest that combining mesoporous silica nanocarriers and submcrometric cavitation nuclei may help enhance the extravasation of the nanocarrier, thus enabling subsequent sustained drug release to happen from those particles already embedded in the tumour tissue.

In vitro and in vivo evaluation of controlled-release matrix tablets of highly water-soluble drug applying different mw polyethylene oxides (PEO) as retardants

The aim of the work presented is to prepare a controlled-release hydrophilic matrix tablet (CMT) controlling release of highly water-soluble drug applying pure combination of high- and low-Mw PEO as matrix materials, to avoid the lag time of drug release, and to overcome incomplete release in later stages. The influences of types and amounts of different Mw PEOs used, drug loading, pH of release medium and agitation rate on drug release were evaluated. The study of uptake and erosion of matrix was conducted and mechanism of improving drug release was discussed. In vivo pharmacokinetics of the CMT and reference preparation self-made controlled-release osmotic pump tablets (COPT) were performed in beagle dogs. The optimized formulation containing 43% PEO WSR 303 and 32% PEO N750 showed a zero order release from 1 h to 12 h. In vivo results demonstrated that the CMT had similar AUC0-48 h and Cmax with the COPT but smaller Tmax than the COPT and provided a more stable therapeutic concentration compared to the COPT. In conclusion, hydrophilic matrix tablet combining only different Mw PEOs as matrix materials had very good potential to be developed into a controlled-release drug delivery system for highly water-soluble drug. Besides, its manufacturing processes were succinct which would be preferable for modern medicine industry.

Biocompatible Polymeric Nanoparticles From Castor Oil Derivatives via Thiol‐Ene Miniemulsion Polymerization

Biocompatible polymeric nanoparticles are obtained via thiol‐ene polymerization of a biobased monomer in miniemulsion. The α,ω‐diene‐diester monomer is synthesized through esterification reaction of a glycerol derivative, namely 1,3‐propanediol, with 10‐undecenoic acid, a long‐chain diene carboxylic acid. In order to investigate how different monomeric structures behave toward thiol‐ene polymerization in miniemulsion, two types of thiols are investigated: 1,4‐butanedithiol and 2‐mercaptoethyl ether. Poly(thioether‐ester)s with weight average molecular weight up to 15 kDa (Mn) are obtained, depending on initiator concentration and types of surfactant and dithiol employed. Finally, biobased poly(thioether‐ester) nanoparticles are submitted to cytotoxicity and hemolysis analyses. High cell viability and no significant changes in cell morphology are observed after the incubation on murine fibroblast (L929) and human cervical cancer cells (HeLa). Last, hemolysis assays revealed blood compatibility and therefore polymeric nanoparticles have been shown to be a potential alternative drug delivery vector for intravenous administration.Practical Applications: There is a great demand for polymeric systems that fulfill a number of requirements, such as biodegradability and biocompatibility, for biomedical applications. In this context, biobased polymers obtained from vegetable oils are a very attractive sustainable alternative to fossil‐derived polymeric materials, presenting potential biodegradability and low toxicity. By thiol‐ene reactions, polymeric materials containing ester groups in the main chain—which can undergo hydrolysis—can be prepared in miniemulsion, enabling their degradation in physiological environment and, therefore, being interesting for biomedical applications and material disposal. Such novel materials could be used in temporary implants, tissue engineering, and drug delivery systems.Biocompatible polymeric nanoparticles are obtained via thiol‐ene polymerization of a biobased monomer in miniemulsion. Nanoparticles revealed to be a potential alternative controlled release drug delivery vector for intravenous administration.

Enhanced Entrapment and Improved in Vitro Controlled Release of N-Acetyl Cysteine in Hybrid PLGA/Lecithin Nanoparticles Prepared Using a Nanoprecipitation/Self-Assembly Method.

To enhance the in vitro controlled release of N-acetyl cysteine (NAC), hybrid nanoparticles (NPs) consisting of a poly(lactide-co-glycolide) (PLGA) hydrophobic core and a soybean lecithin mono-layer coat were prepared. Hybrid NPs were synthesized using a nanoprecipitation combined with self-assembly method. To characterize prepared NPs, zeta potential, diameter size, surface morphology, disparity, and lipid coating of hybrid NPs were detrmined using dynamic light scattering, scanning electron microscope and Fourier transform infrared spectroscopy techniques. High-performance liquid chromatography was employed to evaluate drug loading yield and encapsulation efficiency and in vitro drug release of prepared NPs. The cytotoxicity of hybrid NPs was assayed on normal L929 alveolar epithelial cells using MTT method. Prepared NPs were found to disperse as individual NPs with a well-defined spherical shape. The hydrodynamic diameter and surface charge of NAC-loaded hybrid NPs were 81.8 ± 1.3 nm and -33.1 ± 2.1 mV, respectively. Drug loading yield and encapsulation efficiency of NAC-loaded hybrid NPs were found to be 38 ± 2.1% and 67 ± 5.7%, respectively. Prepared hybrid NPs showed no significant cytotoxicity against normal alveolar cells. Our data suggest that the hybrid PLGA-lecithin NPs may be An efficient controlled release drug delivery system for NAC. J. Cell. Biochem. 118: 4203-4209, 2017. © 2017 Wiley Periodicals, Inc.

Is it Possible to Treat Osteosarcoma Using Oligonucleotides Confined into Controlled Release Drug Delivery Systems?

The present study aimed to analyze the researches that are at the experimental phase concerning osteosarcoma treatment. The researches included drug delivery systems which allow controlled release and imbue small interfering-/micro- ribonucleic acid. Without any language preference, we searched US National Library of Medicine National Institutes of Health, Embase, OVID, Cochrane Library database of clinical trials from 1843 to May 25, 2016 and traced all the references of incorporated documents. The data were evaluated using descriptive statistics and the results are shown as frequency (%). We haven't encountered any drug delivery system in which Small interfering ribonucleic acid/ micro ribonucleic acid oligonucleotides were embedded successfully against osteosarcoma. There has been only one research in which hairpin-ribonucleic acid was embedded. It was considered that drug delivery system enabling controlled oligonucleotide release in the treatment period of osteosarcoma was not projected for the clinical use. However, it cannot be neglected that the mentioned experimental studies with regard to osteosarcoma treatment establish the basis of target therapies. The method in question looks promising regarding effective treatment of osteosarcoma in the future.

Exploring pullulan-poly(vinyl alcohol) interpenetrating network microspheres as controlled release drug delivery device

In the present study, interpenetrating polymeric network (IPN) microsphere was prepared using glutaraldehyde assisted water-in-oil emulsion crosslinking method for controlled delivery of pirfenidone, the only chemical entity approved by US FDA for the treatment of Idiopathic Pulmonary Fibrosis (IPF). In our study, the natural biopolymer pullulan was harnessed in combination with synthetic polymer PVA for drug delivery applications. The prepared microspheres were characterized by Fourier transform infrared spectroscopy, Raman spectroscopy, solid state 13C nuclear magnetic resonance and field emission scanning electron microscopy. The Ozawa-Flynn-Wall and Kissinger-Akahira-Sunose isoconversional models were employed to calculate the activation energy (Ea) from thermal kinetic study. The prepared microspheres were checked for its non-cytotoxicity and cell viability using MTT assay. Different kinetic models were fitted to explore the release kinetics and mechanism from the delivery device. The prepared microspheres could be a potential candidate for controlled delivery of pirfenidone.

Synthesis of Carboxamide‐Functionalized Multiwall Carbon Nanotubes via Ugi Multicomponent Reaction: Water‐Dispersible Peptidomimetic Nanohybrid as Controlled Drug Delivery Vehicle

AbstractThis paper describes a direct synthesis of novel and valuable carboxamide functionalized multiwall carbon nanotubes (carboxamide‐f‐MWCNTs) for the development of new nanovectors through covalent functionalization via a one‐pot four‐component Ugi reaction. This efficient synthetic approach is facile and straightforward procedure for the synthesis of peptidomimetic coated MWCNTs from simple and readily starting materials including aniline, benzaldehyde, isocyanide and the carboxylated MWCNT as an acid component. The new synthesized nanobiohybrid was fully characterized. Also, the stability of nanobiohybrid was assessed using Zeta potential and particle size analyses. The synthesized nanobiohybrid presents unprecedented high and long term dispersity and stability in water. The performance of the nanobiohybrid for the controlled release of folic acid, as a model drug, was investigated and the results depicted pH dependent slow drug release behavior of nanobiohybrid. In addition, biocompatibility and cytotoxicity of carboxamide‐f‐MWCNTs were examined and no obvious adverse effects on the viability of NIH‐3T3 cells were observed. The results manifested its valuable applicability in controlled release drug delivery systems.

Review on Microsponges As a Novel Drug Delivery System

Microsponge can be effectively incorporated into oral delivery of drugs using bio erodible polymer’s especially for colon specific delivery and also use for topical drug delivery system for retention of dosage form on skin and controlled release drug delivery system thus improving patient compliance by proving site specific drug delivery system and prolonging dosage intervals. The microsponge consists of myriad of interconnecting voids within non- collapsible structures with a large porous surface. The size of Micro sponges can be varied usually from 5-300 μm in diameter. The outer surface is typically porous, allowing the sustained flow of substances out of the sphere. Microsponge delivery system (MDS) can provide increased efficacy for topically active agents with enhanced safety, extended product stability, enhanced formulation flexibility , reduced side effects and improved aesthetic properties in an efficient and novel manner In addition these are non-mutagenic, non allergic, and non-toxic . The present review introduces Microsponge technology along with its synthesis, characterization, programmable parameters and release mechanism of MDS

Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue

PurposePolyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers.MethodsAnionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS).ResultsDendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies.ConclusionsPAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

The Research Progress of Targeted Drug Delivery Systems

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Controlled release drug delivery via polymeric microspheres: a neat application of the spherical diffusion equation

ABSTRACTVarious applied mathematics undergraduate skills are demonstrated via an adaptation of Crank's axisymmetric spherical diffusion model. By the introduction of a one-parameter Heaviside initial condition, the pharmaceutically problematic initial mass flux is attenuated. Quantities germane to the pharmaceutical industry are examined and the model is tested with data derived from industry journals. A binomial algorithm for the acceleration of alternating sequences is demonstrated. The model is accompanied by a MAPLE worksheet for further student exploration.

A Review of the Structure, Preparation, and Application of NLCs, PNPs, and PLNs.

Nanostructured lipid carriers (NLCs) are modified solid lipid nanoparticles (SLNs) that retain the characteristics of the SLN, improve drug stability and loading capacity, and prevent drug leakage. Polymer nanoparticles (PNPs) are an important component of drug delivery. These nanoparticles can effectively direct drug delivery to specific targets and improve drug stability and controlled drug release. Lipid–polymer nanoparticles (PLNs), a new type of carrier that combines liposomes and polymers, have been employed in recent years. These nanoparticles possess the complementary advantages of PNPs and liposomes. A PLN is composed of a core–shell structure; the polymer core provides a stable structure, and the phospholipid shell offers good biocompatibility. As such, the two components increase the drug encapsulation efficiency rate, facilitate surface modification, and prevent leakage of water-soluble drugs. Hence, we have reviewed the current state of development for the NLCs’, PNPs’, and PLNs’ structures, preparation, and applications over the past five years, to provide the basis for further study on a controlled release drug delivery system.

Synthesis and characterization of psyllium seed mucilage grafted with N,N-methylene bisacrylamide

Psyllium seed polysaccharide was modified to investigate its use as multifunctional pharmaceutical excipient. The objective of this study was isolation of psyllium seed polysaccharide and crosslinking with acrylic acid using N,N-methylene bisacrylamide and its characterization. Acrylic acid was used as monomer and ammonium persulfate as initiator. A full factorial design was employed to optimize the crosslinking. The modified polysaccharide was characterized by FTIR, DSC, PXRD, loss on drying, pH, viscosity, micromeritics properties and swelling studies in 0.1N HCl, 0.5N NaOH, phosphate buffer pH 6.8. It was observed that swelling of crosslinked polysaccharide increased with decreased concentration of monomer and increasing concentration of crosslinker. Greater degree of grafting was observed with increase in crosslinker and monomer concentration. Dispersions of 1% w/v of PPS and APPS show pseudoplastic behavior. No clinical signs of toxicity were evident in repeat dose toxicity studies conducted in rats. Administration of up to 350mg/kg/day of APPS was well tolerated by the animals. Modification of psyllium via graft copolymerization and network formation with the crosslinker, improved the property profile and utility of psyllium polysaccharide. The modified polysaccharide can be used for designing controlled release drug delivery systems due to its swelling ability.

Scaffold composed of porous vancomycin-loaded poly(lactide-co-glycolide) microspheres: A controlled-release drug delivery system with shape-memory effect

Loading antibiotics in a biodegradable polymer matrix is an excellent way to control its release kinetics, which eliminates side effects caused by conventional administrations of the drug. This approach is especially beneficial for bone regeneration when using a scaffold made of a biodegradable polymer loaded with drug agents capable of controllable releases. In this case, the scaffold serves as a mechanical support to tissue formation and the drug agents may provide biomolecules to assist the tissue formation and/or provide antibiotics to prevent tissues from infections. Towards this goal, we have developed an approach to make vancomycin-loaded poly(lactide-co-glycolide) (PLGA) microspheres, from which we made scaffolds by compression molding. In this article we concentrate on characterizing the porosity and drug release profiles, as well as verifying shape-memory effect of the scaffolds. The scaffold was biodegradable and showed a much slower drug release profile than microspheres. We confirmed that our PLGA scaffolds recovered to their permanent shapes when heated to 45°C. We believe that these scaffolds will find applications in bone regeneration where both the use of antibiotics against infection and accommodation to spatial restrictions may be required.

Novel class of nanofiber hydrogels based on the biodegradable amphiphilic copolymers poly(sarcosine) and poly(l-lactic acid) and prepared using alcohols

Route of preparation can be an important step in producing safe and effective controlled-release drug vehicles. We now describe a novel class of hydrogels based on biodegradable amphiphilic polymers consisting of hydrophobic poly(l-lactic acid) and hydrophilic poly(sarcosine). The hydrogels were prepared by initially dissolving the polymers in methanol, ethanol, and butanol, which are also amphiphilic. Transmission electron microscopy revealed that the hydrogels consist of self-assembled nanofibers, with a dynamic modulus greater than the loss elastic modulus over a range of stress cycles at different frequencies. Differential scanning calorimetry indicated that the hydrogels contain stable poly(l-lactic acid) crystals. Importantly, the hydrogels did not elicit irritation in a 3D model of the human corneal epithelia, and suppressed, by more than 20%, the initial drug burst typically associated with controlled-release vehicles already on the market. Hence, the hydrogels show promise as a new class of controlled-release drug delivery systems.