Development Of Drug Delivery Systems Research Articles

Advanced Drug Delivery-Inhalation of Nanoparticles to Treat Coronary Failure

Drug delivery is a technology and a system for transforming a pharmaceutical compound to achieve its therapeutic effect. Now a day’s drug delivery include development of target delivery in which drug is active in targeted area of body[14]. Heart failure also called as coronary heart failure. Heart failure is an abnormality occurs when muscles dose not pump sufficient blood to maintain blood flow. Lifestyle changes, medications, pacemakers, defibrillators and even open heart surgery can be used to treat heart failure[1]. Now days the developed drug delivery system inhalation of nanoparticles used to cure heart failure. Nanoparticles are small objects designed as vehicles for small molecules to provide a therapeutic stimulus at target. Nanoparticles reduce toxicity and side effects of drug. Nanoparticles inhalation is most effective drug delivery than other delivery types like oral, injection routes, ocular route etc[7].The important advantage of nanoparticles used of nanoparticles used as drug carrier is highly stable and have high carrier capacity[5].

A Review on Novel Drug Delivery System: Microsponges

Recent research on idealizing drug delivery system which is progressing at a prodigious rate and aims at development of drug delivery system (DDS), with maximum therapeutic advantages of drug delivery, thus resulting in safe and effective management of disease. More and more developments in delivery systems are being integrated to optimize the efficacy and cost effectiveness of the therapy. New classes of pharmaceuticals, biopharmaceuticals are fueling the rapid evolution of drug delivery technology. Microsponge technology has been introduced in topical drug products to facilitate the controlled release of active drug into the skin in order to reduce systemic exposure and minimize local cutaneous reactions to active drugs. Microsponge consists of microporous beads loaded with active agent. When applied to the skin, the microsponge releases its active ingredient on a time mode and also in response to other stimuli (rubbing, temperature, pH etc.) that are used mostly for topical and recently for oral administration Microsponges are porous, polymeric microspheres that are mostly used for prolonged topical administration. Microsponges are designed to deliver a pharmaceutically active ingredient efficiently at minimum dose and also to enhance stability, reduce side effects, and modify drug release profiles. Microsponges are prepared by several methods utilizing emulsion system or by suspension polymerization in a liquid–liquid system. The most common emulsion system used is oil-in-water (o/w), with the microsponges being produced by the emulsion solvent diffusion (ESD) method. 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-irritating, non-mutagenic, non-allergenic, and nontoxic. The present review introduces microsponge technology in great detail.

Hyaluronic Acid-Based pH-Sensitive Polymer-Modified Liposomes for Cell-Specific Intracellular Drug Delivery Systems.

For the enhancement of therapeutic effects and reduction of side effects derived from anticancer drugs in cancer chemotherapy, it is imperative to develop drug delivery systems with cancer-specificity and controlled release function inside cancer cells. pH-sensitive liposomes are useful as an intracellular drug delivery system because of their abilities to transfer their contents into the cell interior through fusion or destabilization of endosome, which has weakly acidic environment. We earlier reported liposomes modified with various types of pH-sensitive polymers based on synthetic polymers and biopolymers as vehicles for intracellular drug delivery systems. In this study, hyaluronic acid (HA)-based pH-sensitive polymers were designed as multifunctional polymers having not only pH-sensitivity but also targeting properties to cells expressing CD44, which is known as a cancer cell surface marker. Carboxyl group-introduced HA derivatives of two types, MGlu-HA and CHex-HA, which have a more hydrophobic side chain structure than that of MGlu-HA, were synthesized by reaction with various dicarboxylic anhydrides. These polymer-modified liposomes were stable at neutral pH, but showed content release under weakly acidic conditions. CHex-HA-modified liposomes delivered their contents into CD44-expressing cells more efficiently than HA-modified or MGlu-HA-modified liposomes or unmodified liposomes, whereas the same liposomes were taken up only slightly by cells expressing CD44 proteins less. Competition assay using free HA or other polymers revealed that HA derivative-modified liposomes might be recognized by CD44. Therefore, HA-derivative-modified liposomes are useful as cell-specific intracellular drug delivery systems.

Photo-responsive nanoparticles for β-lapachone delivery in vitro

Drug efficiency delivery and release to target site play an important role in the treatment of cancer. To achieve these goals, developing drug delivery systems is the key step. The common materials used for drug delivery like liposomes, micelles, dendrimers cannot control the delivery and releasing by spatial and temporal. In this paper, we design a photoresponsive drug delivery system to reduce the side effects of traditional chemotherapy on normal cells and improve therapeutic efficacy in treating cancers. We synthesized two kinds of photo-responsive polymers using two different monomers containing two photoresponsive groups. The two monomers were crosslinked by poly (ethylene glycol) dimethacrylate to form polymers and then encapsulated β-lapachone into the nanoparticles, after UV irradiation, the particle will degrade and release the drug. This method may provide new strategies for the photoresponsive nanomaterials.

In-Vitro Assessment of Magnetic Dextran-Spermine Nanoparticles for Capecitabine Delivery to Cancerous Cells.

Cationic polymeric nanoparticles have great potential for developing drug delivery systems with limited side effects for tumor medication. The goal of this research is investigation of cationic dextran-spermine polymer (DS) efficacy for improvement of hydrophilic drug delivery to negatively charged cancerous cells. Capecitabine (as a hydrophilic antineoplastic drug) was loaded into the magnetic dextran-spermine nanoparticles (DS-NPs) via ionic gelation. Design of experiments was applied to specify how the significant factors affect size, surface charge and capecitabine entrapment efficiency of the DS-NPs. Physicochemical properties, in-vitro release profile and cellular studies of the optimized DS-NPs were evaluated. The experimental results indicated that DS-NPs with favorable properties can be achieved at an optimized condition of 2 mg/mL DS and 0.75 mg/mL tri-polyphosphate (TPP) concentrations, TPP addition rate of 35 mL/min, pH 3 of DS solution and super paramagnetic iron oxide nanoparticles (SPION)/DS mass ratio of 0.5. The entrapment efficiency of capecitabine was 26.1% at optimum condition and drug release at neutral pH after 24 h and acidic pH within 3 h was 56 and 98%, respectively. The cytotoxicity assessment exhibited that capecitabine loaded DS-NPs was more toxic than corresponding free drug as control. Significant cellular uptake of capecitabine loaded DS-NPs by U87MG glioblastoma cells were proved by Prussian blue staining and TEM, qualitatively. DS-NPs are suitable candidates for delivery of the hydrophilic drugs in cancer treatment and due to positive charge of the dextran-spermine, the uptake of the hydrophilic drugs by the cancerous cells was improved.

Core/shell microencapsulation of indomethacin/paracetamol by co-axial electrohydrodynamic atomization

Core/shell microparticles for development of drug delivery systems were prepared using co-axial electrohydrodynamic atomization technique in order to develop fixed dose combined formulations incorporating paracetamol and indomethacin as model drugs. The developed drug delivery systems offered successful co-encapsulation of paracetamol and indomethacin with high drug encapsulation efficiencies of 54% and 69% for paracetamol and indomethacin, respectively. The developed formulations were further characterised with respect to their morphology, drug release profile and possible interactions. In comparison to the release rate of the free indomethacin, the developed formulation resulted in enhanced dissolution rate of indomethacin. This study demonstrates a versatile polymeric platform where multiple drug encapsulation and co-delivery is made possible by utilizing co-axial electrohydrodynamic atomization. The proposed system offered high processing yield of 60–70%, as a single-step platform for preparation of fixed dose formulations for oral drug delivery, particularly in geriatric therapy.

NGR-modified pH-sensitive liposomes for controlled release and tumor target delivery of docetaxel

As current tumor chemotherapy faces many challenges, it is important to develop drug delivery systems with increased tumor-targeting ability, enhanced therapeutic effects and reduced side effects. In this study, a pH-sensitive liposome was constructed containing CHEMS-anchored PEG2000 for extended circulation and NGR peptide as the targeting moiety. The NGR-modified docetaxel-loaded pH-sensitive extended-circulation liposomes (DTX/NGR-PLL) prepared possess suitable physiochemical properties, including particle size of approximately 200nm, drug encapsulation efficiency of approximately 70%, and pH-sensitive drug release properties. Experiments performed in vitro and in vivo on human fibrosarcoma cells (HT-1080) and human breast adenocarcinoma cells (MCF-7) verified the specific targeting ability and enhanced antitumor activity to HT-1080 cells. The results of intravenous administration demonstrated that NGR-modified liposomes can significantly and safely accumulate in tumor tissue in xenografted nude mice. In conclusion, the liposomes constructed hold promise as a safe and efficient drug delivery system for specific tumor treatment.

Adsorption and desorption of curcumin by poly(vinyl) alcohol-multiwalled carbon nanotubes (PVA-MWCNT)

Carbon nanotubes (CNT) are among the most striking discoveries in the search for new materials as drug delivery carrier. In the present work, multiwalled CNT (MWCNT) functionalized with polyvinyl alcohol (PVA) was developed as a potential carrier for Curcumin (Cur). The aim was to investigate its loading and release efficiency in vitro. To achieve this goal, pristine MWCNT (p-MWCNT) was firstly oxidized by acids and functionalized with PVA. Next, systematic evaluation of Cur loading efficiency on PVA-MWCNT was determined using adsorption kinetics and isotherm studies and was compared to p-MWCNT and oxidized-MWCNT (ox-MWCNT). The release of Cur was analyzed in physiological buffer pH 7.4 and 5.5. From the results, all MWCNT adsorbed Cur rapidly and well described by the pseudo-second order model. The isotherm results suggest that the PVA-MWCNT and p-MWCNT obey Freundlich isotherm model with maximum Cur adsorption (kf) of 5.1 and 69.0 mg/g, respectively, while Cur adsorption on ox-MWCNT followed Langmuir isotherm model with maximum adsorption (qm) of 714.3 mg/g. Cur desorbed significantly (25–30%) from PVA-MWCNT at pH 5.5 than that of pH 7.4, with a sustained release over 3 days of incubation. The results suggest its weak binding interaction to the PVA-MWCNT has facilitated its release at lower pH, compared to ox-MWCNT that occurred via chemisorption. The p-MWCNT ranked the lowest with 4–6% Cur released at both pHs. Overall, the initially developed drug delivery system was considered successful for loading and the release of Cur, which potentially benefit disorders related to cancer or oxidative-related injuries in the future.

Antibacterial PHAs coating for titanium implants

Biomaterial-associated infection is a serious complication of modern implantation surgery. Thus, the improvement of implant surfaces is required to avoid the first stage for biofilm formation, bacterial adhesion. The current research addresses this issue by developing drug delivery systems (DDS) consisting of antibiotic-loaded polyhydroxyalkanoates (PHAs) coatings on titanium implants. Dip-coating technique was used to achieve optimal coatings with biodegradable biopolyesters, polyhydroxybutyrate (PHB) and its copolymer, polyhydroxybutyrate-co-hydroxyvalerate (PHBV). The coatings were completely characterized (wettability, topography, thickness and roughness), and studies of drug delivery, toxicity, antibacterial effect, and cell adhesion were performed. For both of biopolymers, surfaces were partially covered with 1 and 3 immersions, while with 6, they were completely covered. Although both antibiotic-loaded biopolymer coatings assure the protection against bacteria populations, PHBV coatings are closer to the desired release profile; its faster degradation provides for a greater and more stable drug release for a given period of time compared to PHB coatings. The use of coatings with different drug concentration per layer results in more controlled and homogeneous releases. The DDS designed not only assure to avoid the first stage of bacterial adhesion, but also their proliferation and biofilm formation, since the coatings degrade with time under physiological conditions, guaranteeing a prolonged drug release.

Formulation And In Vitro/In Vivo Evaluation Of Olmesartan Medoxomil Solid Dispersions Incorporated E/R Trilayer Matrix Tablets By Geomatrix

<p>An attempt has been made to develop and optimize an novel anti hypertensive trilayered controlled release matrix tablets incorporated with Olmesartan medoxomil solid dispersion prepared by direct compression and consisted of middle active layer with different grades of hydroxypropylmethylcellulose (HPMC), guar gum, ethyl cellulose. Upper and lower layers are prepared with Carnauba wax, guar gum and sodium CMC. The developed drug delivery system provided prolonged drug release rates over a period of 24 h. The release profile of the optimized formulation (HF14) was described by the Zero-order and Higuchi model. In-vivo bioavailability studies were carried out with the optimized formulation (HF14) and reference standard A fair correlation between the dissolution profile and bioavailability for the optimized formulation was observed. The results indicate that the approach used could lead to a successful development of a trilayer extended release formulation up to 24h. These results also demonstrated that the Olmesartan solid dispersion incorporated trilayer tablets shown more bioavailability because of its conversion from crystalline to amorphous form.</p>

Honeycomb structural composite polymer network of gelatin and functional cellulose ester for controlled release of omeprazole

The functionalized cellulose ester MCN was firstly synthesized and used to cross-link gelatin by amidation between −NH2 in gelatin and active ester groups in MCN to form a composite polymer network Gel-MCN, which was confirmed by Van Slyke method, FTIR, XRD and TGA-DTG spectra. The model drug omeprazole was loaded in Gel-MCN composites mainly by electrostatic interaction and hydrogen bonds, which were certified by FTIR, XRD and TGA-DSC. Thermal stability, anti-biodegradability, mechanical property and surface hydrophobicity of the composites with different cross-linking extents and drug loading were systematically investigated. SEM images demonstrated the honeycomb structural cells of cross-linked gelatin networks and this ensured drug entrapment. The drug release mechanism was dominated by a combined effect of diffusion and degradation, and the release rate decreased with cross-linking degree increased. The developed drug delivery system had profound significance in improving pesticide effect and bioavailability of drugs.

In Vivo Tracking of Extracellular Vesicles in Mice Using Fusion Protein Comprising Lactadherin and Gaussia Luciferase.

Extracellular vesicles (EVs) are cell-derived vesicles comprising a lipid bilayer and are found in body fluids, such as blood, sweat, and urine. As EVs, especially exosomes, function as endogenous intercellular delivery tools, their roles in various biological events have been extensively investigated. In addition, they are expected to become safe and effective drug delivery systems (DDS) because of their intrinsic nature. In the development of EV-based DDS, as well as in the investigation of the biological functions of EVs, it is important to analyze the in vivo behavior of EVs by tracking them. Therefore, we have developed a sensitive EV-labeling method to track EVs in vivo by designing a fusion protein comprising lactadherin (LA) (alias milk fat globule-EGF factor 8), a protein that binds to EV membranes through interaction with phosphatidylserine, and Gaussia luciferase (gLuc), a chemiluminescent protein. gLuc-LA-labeled EVs are easily obtained by transfecting EV-producing cells with a gLuc-LA-encoding plasmid vector. Here, we describe methods to label EVs with the fusion protein and to track the labeled EVs in vivo.

Simultaneous monitoring of the drug release and antitumor effect of a novel drug delivery system-MWCNTs/DOX/TC

Monitoring drug release and therapeutic efficacy is crucial for developing drug delivery systems. Our preliminary study demonstrated that, as compared with pristine multiwalled carbon nanotubes (MWCNTs), transactivator of transcription (TAT)-chitosan functionalized MWCNTs (MWCNTs-TC) were a more promising candidate for drug delivery in cancer therapy. In the present study, a MWCNTs/TC-based drug delivery system was developed for an anticancer drug, doxorubicin (DOX). The drug loading and in vitro release profiles, cellular uptake and cytotoxicity were assessed. More importantly, the in vivo drug release and antitumor effect of MWCNTs/DOX/TC were evaluated by noninvasive fluorescence and bioluminescence imaging. It was demonstrated that MWCNTs/DOX/TC can be efficiently taken up by BEL-7402 hepatoma cells. The release of DOX from MWCNTs/DOX/TC was faster under lower pH condition, which was beneficial for intrcellular drug release. The in vivo release process of DOX and antitumor effect in animal model were monitored simultaneously by noninvasive fluorescence and luminescence imaging, which demonstrated the application potential of MWCNTs/DOX/TC for cancer therapy.

Triblock copolymers for nano-sized drug delivery systems

Triblock copolymers have been widely used as a material for developing drug delivery systems (DDS). In terms of architecture, triblock copolymers could be classified into symmetric and asymmetric triblock copolymers. Different types of nano-sized structures such as star micelles, flower-like micelles, and polymer vesicles could be prepared from these block copolymers, which would be very potential in delivering various types of agents such as chemical drugs, genes, and contrast agents. Additionally, the nano-sized carriers have been fabricated for environmentally sensitive (pH-sensitive or temperature sensitive) DDS or for enhancing the gene delivery efficiency. Due to their versatility in structures and drug delivery capacity, the application of triblock copolymers would definitely be expanded in near future.

In Vitro - In Vivo Evaluation Of E/R Trilayer Matrix Tablets Containing Solid Dispersion Of Atorvastatin

<p>Investigation of <em>in vitro/in vivo</em> behaviour of extended release tablets containing solid dispersions of Atorvastatin is the focus of the present research work. Atorvastatin trilayer matrix tablets were prepared by direct compression method and consisted of middle active layer with different grades of hydroxypropylmethylcellulose (HPMC), ethyl cellulose and Carbopol 934P. Barrier layers are prepared with hydrophobic polymers carnauba wax and xanthan gum. Based on the evaluation parameters, drug dissolution profile and release order kinetics HF16 was found to be optimized formulation. The developed drug delivery system provided prolonged drug release rates over a period of 24 h. The release profile of the optimized formulation (HF16) was described by the Zero-order and best fitted to Higuchi model. FTIR confirmed that there was no chemical interaction between drug and excipients used in the formulation. . In vivo bioavailability studies were conducted for optimized formulation HF16 and reference standard. The optimized formulation of Atorvastatin trilayer matrix tablet was shown significant plasma concentration with extended release and maintained for 24 hrs with patient compliance by reducing the dosage frequency, when compared with reference standard. </p>

Researchers develop drug delivery system to slow and control tumors

Researchers develop drug delivery system to slow and control tumors

Programmed near-infrared light-responsive drug delivery system for combined magnetic tumor-targeting magnetic resonance imaging and chemo-phototherapy.

As we all know, a series of shortcomings of conventional chemotherapy such as limited stability, rapid clearing and non-specific tumor targeting ability remain a significant challenge to achieve successful clinical therapeutic efficiency in cancer treatments. Fortunately, developing drug delivery system under the assistance of multifunctional nanocarries might be a great idea. For the first time, we proposed an intelligent drug delivery system by capping DOX-loaded hollow mesoporous CuS nanoparticles (HMCuS NPs) with multifunctional IONPs to integrate programmed functions including enhanced PTT effect, sophisticated controlled drug release, magnetic targeting property and MR imaging. The results showed HMCuS/DOX@IONP-PEG could significantly enhance anti-tumor therapeutic efficacy due to the synergistic combination of chemo-phototherapy. By this delicate design, we believe such smart and extreme versatile all-in-one drug delivery platform could arouse broad interests in the fields of biomaterials, nanotechnology, and drug delivery system.

Development of oral site-specific pellets containing flavonoid extract with antioxidant activity

Herbal medicines are recognized as an effective treatment of common diseases, mainly associated with oxidative stress. Therefore developing drug delivery systems of these biological active ingredients are gaining interest. Parsley (Petroselinum crispum L.) is a well-known culinary herb and its leaf contains high amount of apigenin, therefore it is suitable as a natural source of this flavonoid. Apigenin possess many health effects such as antioxidant, anti-inflammatory and anticancer activities. Unfortunately, these benefits are limited due to the low water solubility and bioavailability, it was recently classified as BCS II group compound. Therefore the aim of this study was to develop a carrier system for Petroselinum crispum extract, containing high amount of apigenin. Microcrystalline cellulose inert pellet cores were chosen and enteric coatings were applied. The produced multiparticulates had spherical shape, narrow size distribution and low moisture content. 10% (w/w) Eudragit® L 30 D-55 and 15% (w/w) Eudragit® FS 30 D coating was adequate for the modified release in vitro. The layered pellets demonstrated antioxidant activity. It was concluded that development of oral site-specific pellets containing flavonoid extract successful and the therapeutic effectiveness could be hypothesized.

Drug self-delivery systems for cancer therapy.

Carrier-assistant drug delivery systems (DDSs) have been rapidly established for cancer therapy and great strides have been made in recent years. However, further development of DDSs is retarded by the aspects such as the low drug carrying capacity, carrier-induced toxicity and immunogenicity, complex synthesis manipulation. Drug self-delivery systems (DSDSs), in which active drugs exhibit nanoscale characteristic to realize intracellular delivery by themselves without the help of nanocarriers, have been rapidly developed to address these issues. In this review, we present a comprehensive summary of the recent advances in DSDSs for cancer therapy. After a brief introduction to the major types of DSDSs and their fabrication strategies, we emphatically discuss some representative achievements of these DSDSs for passive or/and positive targeting therapy, combinational therapy as well as theranostics. The design principle is explained and justified, which can cast a new light on developing drug delivery systems for cancer treatments.

VEGF- and VEGFR2-Targeted Liposomes for Cisplatin Delivery to Glioma Cells

Targeted delivery of anticancer drugs to brain tumors, especially glioblastoma multiforme, which is the most frequent and aggressive type, is one of the important objectives in nanomedicine. Vascular endothelial growth factor (VEGF) and its receptor type II (VEGFR2) are promising targets because they are overexpressed by not only core tumor cells but also by migrated glioma cells, which are responsible for resistance and rapid progression of brain tumors. The purpose of the present study was to develop the liposomal drug delivery system combining enhanced loading capacity of cisplatin and high binding affinity to glioma cells. This was achieved by using of highly soluble cisplatin analogue, cis-diamminedinitratoplatinum(II), and antibodies against the native form of VEGF or VEGFR2 conjugated to liposome surface. The developed drug delivery system revealed sustained drug release profile, high affinity to antigens, and increased uptake by glioma C6 and U-87 MG cells. Pharmacokinetic study on glioma C6-bearing rats revealed prolonged blood circulation time of the liposomal formulation. The above features enabled the present drug delivery system to overcome both poor pharmacokinetics typical for platinum formulations and low loading capacity typical for conventional liposomal cisplatin formulations.