Polymeric Carrier Systems Research Articles

Kinetic study of in vitro release of curcumin from chitosan biopolymer and the evaluation of biological efficacy

Sustained release of curcumin from the polymeric carrier system chitosan, a natural biopolymer material derived from chitin originated from natural shrimp shell waste, was studied. Six kinetic models, zero order, first order, Korsmeyer–Peppas (KP), Peppas – Sahlin (PS), Higuchi, and Hixson–Crowell, were applied to study the drug release kinetics. The release mechanism of the drug from the curcumin-chitosan composite was evaluated by changing the pH, ionic strength of the release media, and drug concentration. KP and PS models were selected among the studied models to investigate the drug release mechanism from the chitosan biopolymer based on the R2 values (R2 > 0.99). The model constants m in the PS model and n in the KP model stand for the case II relaxation and Fickian diffusion contribution, respectively. The n being < 0.43 in the KP model suggests that the Fickian diffusion governs the drug release. Furthermore, there is a noticeable difference between the values obtained for model parameters m and n in the PS and KP models, indicating that Case II relaxation and Fickian diffusion play crucial roles in the curcumin release mechanism from chitosan. Polymer relaxation has been proven to play a predominant role in releasing curcumin from the composite at lower ionic strengths and higher pH values. Anti-inflammatory activity was tested using the egg-albumin denaturation assay, and the diphenyl-2-picrylhydrazyl assay was carried out to determine the antioxidant activity of the composite. The composite material showed IC50 values of 0.29 mg/ mL and 1.08 mg/ mL for anti-inflammatory and anti-oxidant activities, respectively. The drug composite has shown antibacterial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus, which are highly effective against S.aureus. The resulting inhibition zones for S.aureus were 13.34 ± 0.34 mm, 16.34 ± 0.60 mm, and 13.34 ± 0.73 mm for 5, 10, and 20 mg/ml concentrations, respectively. The drug composite’s minimum inhibitory concentration/ minimum bactericidal concentration ratio for S.aureus, K. pneumoniae, and P.aeruginosa was greater than 4, suggesting that they cause bacteriostatic effects.

Physicochemical Features and Applicability of Newly Fabricated Phytopharmaceutical-Loaded Hydrogel Alginate Microcarriers with Viscoelastic Polyelectrolyte Coatings.

The design of novel polymeric carrier systems with functional coatings is of great interest for delivering various bioactive molecules. Microcapsules coated with polyelectrolyte (PE) films provide additional functionality and fine-tuning advantages essential for controlled drug release. We developed hydrogel microcarriers coated with functional PE films with encapsulated substances of natural origin, resveratrol (RES), curcumin (CUR), and epigallocatechin gallate (EGCG), which have cytotoxic and chemopreventive properties. Alginate (ALG) based microparticles were loaded with phytopharmaceuticals using the emulsification method, and then their surface was modified with PE coatings, such as chitosan (CHIT) or poly(allylamine hydrochloride) (PAH). The morphology and mean diameter of microcarriers were characterised by scanning electron microscopy, encapsulation efficiency was determined by UV-Vis spectroscopy, whereas the physicochemical properties of functional PE layers were studied using quartz crystal microbalance with dissipation monitoring and streaming potential measurements. The release profiles of active compounds from the hydrogel microparticles were described using the Peppas-Sahlin model. The cytotoxic effect of designed delivery systems was studied by evaluating their impact on the proliferation, mitochondrial metabolic function, and lipid peroxidation level of 5637 human bladder cancer cells. The present work demonstrates that the physicochemical and biological features of fabricated microcarriers can be controlled by the type of encapsulated anti-cancer agent and PE coating.

Novel Natrosol/Pectin-co-poly (acrylate) based pH-responsive polymeric carrier system for controlled delivery of Tapentadol Hydrochloride

Background & ObjectivesThis study aimed to create a controlled delivery system for Tapentadol Hydrochloride by developing interpenetrating networks (IPNs) of Natrosol-Pectin copolymerized with Acrylic Acid and Methylene bisacrylamide, and to analyze the effects of various ingredients on the physical and chemical characteristics of the IPNs. MethodsNovel Tapentadol Hydrochloride-loaded Natrosol-Pectin based IPNs were formulated by using the free radical polymerization technique. Co-polymerization of Acrylic Acid (AA) with Natrosol and Pectin was performed by using Methylene bisacrylamide (MBA). Ammonium persulfate (APS) was used as the initiator of crosslinking process. The impact of ingredients i.e. Natrosol, Pectin, MBA, and Acrylic Acid on the gel fraction, porosity, swelling (%), drug loading, and drug release was investigated. FTIR, DSC, TGA, SEM and EDX studies were conducted to confirm the grafting of polymers and to evaluate the thermal stability and surface morphology of the developed IPNs. ResultsSwelling studies exhibited an increase in swelling percentage from 84.27 to 91.17% upon increasing polymer (Natrosol and Pectin) contents. An increase in MBA contents resulted in a decrease in swelling from 85 to 67.63%. Moreover, the swelling was also observed to increase with higher AA contents. Significant drug release was noted at higher pH instead of gastric pH value. Oral toxicological studies revealed the nontoxic and biocompatible nature of Natrosol-Pectin IPNs. Interpretation & ConclusionThe developed IPNs were found to be an excellent system for the controlled delivery of Tapentadol Hydrochloride.

Fabrication of Stimuli-Responsive Quince/Mucin Co-Poly (Methacrylate) Hydrogel Matrices for the Controlled Delivery of Acyclovir Sodium: Design, Characterization and Toxicity Evaluation.

Free-radical polymerization technique was adopted to fabricate a stimuli-responsive intelligent quince/mucin co-poly (methacrylate) hydrogel for the controlled delivery of acyclovir sodium. The developed hydrogel matrices were appraised using different parameters, such as drug loading (%), swelling kinetics, pH- and electrolyte-responsive swelling, and sol-gel fraction. Drug-excipient compatibility study, scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, in vitro drug release studies, drug release kinetics and acute oral toxicity studies were conducted. The results of drug loading revealed an acyclovir sodium loading of 63-75% in different formulations. The hydrogel discs exhibited pH-responsive swelling behavior, showing maximum swelling in a phosphate buffer with a pH of 7.4, but negligible swelling was obvious in an acidic buffer with a pH of 1.2. The swelling kinetics of the developed hydrogel discs exhibited second-order kinetics. Moreover, the hydrogel discs responded to the concentration of electrolytes (CaCl2 and NaCl). The results of the FTIR confirm the formation of the hydrogel via free-radical polymerization. However, the major peaks of acyclovir remain intact, proving drug-excipient compatibility. The results of the SEM analysis reveal the porous, rough surface of the hydrogel discs with multiple cracks and pores over the surface. The results of the PXRD disclose the amorphous nature of the fabricated hydrogel. The dissolution studies showed a minor amount of acyclovir sodium released in an acidic environment, while an extended release up to 36 h in the phosphate buffer was observed. The drug release followed Hixen-Crowell's kinetics with Fickian diffusion mechanism. The toxicity studies demonstrated the non-toxic nature of the polymeric carrier system. Therefore, these results signify the quince/mucin co-poly (methacrylate) hydrogel as a smart material with the potential to deliver acyclovir into the intestine for an extended period of time.

Polymer nanotherapeutics: A versatile platform for effective rheumatoid arthritis therapy.

Rheumatoid arthritis is an aggressive and severely debilitating disorder that is characterized by joint pain and cartilage damage. It restricts mobility in patients, leaving them unable to carry out simple tasks. RA presents itself with severe lasting pain, swelling and stiffness in the joints and may cause permanent disability in patients. Treatment regimens currently employed for rheumatoid arthritis revolve around keeping clinical symptoms like joint pain, inflammation, swelling and stiffness at bay. The current therapeutic interventions in rheumatoid arthritis involve the use of non-steroidal anti-inflammatory drugs, glucocorticoids, disease-modifying anti-rheumatic drugs and newer biological drugs that are engineered for inhibiting the expression of pro-inflammatory mediators. These conventional drugs are plagued with severe adverse effects because of their higher systemic distribution, lack of specificity and higher doses. Oral, intra-articular, and intravenous routes are routinely used for drug delivery which is associated with decreased patient compliance, high cost, poor bioavailability and rapid systemic clearance. All these drawbacks have enticed researchers to create novel strategies for drug delivery, the main approach being nanocarrier-based systems. In this article, we aim to consolidate the remarkable contributions of polymeric carrier systems including microneedle technology and smart trigger-responsive polymeric carriers in the management of rheumatoid arthritis along with its detailed pathophysiology. This review also briefly describes the safety and regulatory aspects of polymer therapeutics.

CRISPR-CAS9 Sisteminde Kullanılan Polimer Bazlı Transfeksiyon Ajanları

Genome editing is a method used to make desired changes in the target gene. Today, various methods are used for genome-editing studies; among them, one of the most widely used methods is the clustered, regularly interspaced short palindromic repeats (CRISPR). CRISPR-associated (Cas) genes and their corresponding CRISPR sequences constitute CRISPR-Cas systems. Due to its simplicity, it is likely that the CRISPR–Cas system could be used effectively in ex vivo gene therapy studies in humans. If this happens, the importance of CRISPR carrier systems will gradually increase. Viral and non-viral systems are used as delivery modalities in genome-editing studies. It has been proven that nanoparticles are the most promising tools for gene therapy due to their adjustable size, surface, shape, and biological behaviours. The polymeric carrier system has become the main non-viral substitute for gene delivery due to its reduced immunogenicity and pathogenicity. In this review, information about current studies related to polymeric carriers used in non-viral CRISPR delivery systems is presented.

Naringin as Sustained Delivery Nanoparticles Ameliorates the Anti-inflammatory Activity in a Freund's Complete Adjuvant-Induced Arthritis Model.

Naringin (NAR), a naturally occurring essential flavonoid, present in grapefruit and Chinese herbal medicines, creates great interest in researchers due to its diverse biological and pharmacological activities. However, further development of NAR is hindered due to its poor water solubility and dissolution rates in GIT. To address these limitations, in this study, we report polymeric nanoparticles (NPs) of NAR (NAR-PLGA-NPs) for enhancing the oral NAR efficiency, with a biodegradable polymer (PLGA) to improve its absorption and bioavailability. NAR-PLGA-NPs were fabricated by a modified solvent emulsification–evaporation technique. Physicochemical properties were evaluated by SEM, particle size distribution, entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). In vitro drug release and ex vivo permeation studies were carried out in phosphate buffer (pH 6.8) for 24 h. Furthermore, in vivo anti-arthritic studies were performed on a mouse model, and the results were compared with free NAR. The modulation of inflammatory mediators was also evidently supported by docking studies. Optimized nanoformulation FN4 (NAR-PLGA-NPs) prepared with acetone–ethanol (2:1) as a solvent system in a combination of stabilizers, i.e., poloxamer-188 and sodium deoxylate (1:1), along with 2% PVA solution, was prepared. From size characterization studies, it was observed that nanoformulations possessed a low particle size (179.7 ± 2.05 nm), a low polydispersity index (0.206 ± 0.001), and a negative zeta potential (−9.18 ± 0.78 mV) with a maximum entrapment efficiency (74 ± 3.61%). The drug release followed a Korsmeyer–Peppas release kinetic model (anomalous non-Fickian diffusion), providing greater NAR release after lyophilization (82.11 ± 3.65%) drug release in pH 6.8 phosphate buffer for 24 h. Ex vivo permeation analysis through an isolated goat intestinal membrane revealed 80.02 ± 3.69% drug release in 24 h. Encapsulation of a drug into PLGA is well described by the results of FTIR, DSC, and XRD. Finally, the therapeutic efficacy of optimized FN4 (NAR-PLGA-NPs) and its possible application on RA were further confirmed in a Freund’s complete adjuvant-induced rat arthritic model as against free NAR at a dose of 20 mg/kg body wt. Our findings demonstrate that sustained action of NAR from optimized FN4 NPs with a rate-controlling polymeric carrier system exhibited prolonged circulation time and reduced arthritic inflammation, hence indicating the possibility as a novel strategy to secure the unpropitious biological interactions of hydrophobic NAR in a gastric environment.

Preparation and evaluation of polymeric beads composed of Chitosan\u2013Gellan Gum\u2013Gum Ghatti/-Gum Karaya polyelectrolyte complexes as polymeric carrier for enteric sustained delivery of Diclofenac sodium

BackgroundAn enteric coating is a multistep technique that involves deposition of a polymeric barrier over uncoated orally administered tablets to prevent them from dissolving or disintegrating in the stomach. However, as soon as the coating dissolves in the alkaline environment of intestine, the whole of the drug come in direct contact with gastric mucosa leading to irritation to distal parts of the gastrointestinal tract (GIT). Considering the above facts, there is clear need to develop a simple and effective enteric release formulation for gastric irritant drugs like Diclofenac sodium (DS). The goal of this study was to create enteric release polymeric polyelectrolyte complex (PEC) beads made up of cationic Chitosan (CH) and anionic Gellan Gum (GG) for sustained DS delivery to the intestine. The beads were prepared by extruding a solution of GG and Gum Ghatti (GT) or GG and Gum Karaya (GK) bearing DS into CH solution in 1% w/v acetic acid, with the help of a syringe fitted with a 18 gauge hypodermic needle.ResultsInstantly created spherical beads were dried in a hot air oven 60 °C overnight. In 0.1 M HCl and 6.8 pH phosphate buffer, the dried beads were tested for drug entrapment in the beads, in vitro swelling of beads and in vitro drug release studies from the beads. The % drug entrapment efficiencies (% DEE) of these PEC beads ranged from 59.54 ± 2.09 to 81.03 ± 4.22%. In 0.1 M HCl, the PEC beads swelled the least in vitro, but expanded significantly in phosphate buffer (pH 6.8). The in vitro release of Diclofenac sodium from different PEC beads in 0.1 M HCl was found to be less than 7.5 percent, whereas the release was sustained for 6 h in phosphate buffer (pH 6.8).ConclusionsFrom the experimental data, it may be concluded that these PEC beads can be useful as potential multiple-unit enteric release polymeric carrier systems for sustained delivery of gastric irritant drugs like Diclofenac sodium.

Porous Polymeric Carrier System for Modified Drug Releaseof Boswellic Acid

Microsponges being the polymeric drug delivery systems consist of porous microspheres that can entrap a wide range of active ingredients. Boswellic acid is a pentacyclic triterpenoid having anti-inflammatory, anti-hypertensive, anti-cancer activities. The aim of the study was to develop, characterize and formulate microsponge delivery for topical application. The Microsponges were prepared by quasi emulsion solvent diffusion method using QbD approach. Drug excipient compatibility study was carried out by FT-IR, DSC and XRD. The prepared Microsponges were further evaluated for its physicochemical properties by scanning electron microscopy (SEM), photomicroscopy, transmission electron microscopy (TEM), particle size, zeta potential, and porosity analysis. The optimized Microsponges were incorporated into gel base formulation and evaluated for in-vitro drug release, dissolution studies and ex-vivo permeability studies. Further, microsponge formulations, subjected for animal studies for skin irritation test and clinical efficacy. The present study confirmed the formation of Microsponges of Boswellic acid. It also proves the sustained release of drug through microsponge formation.

Preparation and characterization of hot-melt extruded polycaprolactone-based filaments intended for 3D-printing of tablets

Hot-melt extruded (HME) filaments are an essential intermediate product for the three- dimensional (3D) printing of drug delivery systems (DDSs) by the fused deposition modelling (FDM) process. The aim of this study was to design novel polymeric 3D-printable HME filaments loaded with active pharmaceutical ingredients (APIs). The physical solid-state properties, mechanical properties, drug release and short-term storage stability of the filaments and 3D-printed DDSs were studied. Physical powder mixtures of polycaprolactone (PCL), plasticizer and API were manually blended, extruded by a single-screw extruder, and printed by a table-top FDM 3D-printing system. The composition of PCL and arabic gum (ARA) enabled the incorporation of 20%, 30% and 40% (w/w) of indomethacin (IND) and theophylline (THEO) into the HME filaments. The uneven distribution of API throughout the filaments impaired 3D printing. The HME filaments loaded with 20% IND or THEO were selected for the further analysis and printing tests (the ratio of PCL, ARA and IND or THEO was 7:1:2, respectively). The IND filaments were yellowish, mechanically strong and flexible, and they had a uniform filament diameter and smooth outer surface. The filaments containing THEO were smooth and off-white. The 3D-printed tablets fabricated from IND or THEO-loaded filaments showed sustained drug release in vitro. The drug release rate, however, significantly increased by changing the geometry of 3D-printed tablets from a conventional tablet structure to an unorthodox lattice (“honeycomb”) structure. Overall, the combination of PCL and ARA provides an interesting novel polymeric carrier system for 3D-printable HME filaments and tablets.

SYNTHESIS, CHARACTERIZATION AND IN VIVO EVALUATION OF PH SENSITIVE HYDROXYPROPYL METHYL CELLULOSE-GRAFT-ACRYLIC ACID HYDROGELS FOR SUSTAINED DRUG RELEASE OF MODEL DRUG NICORANDIL

Background: Anti hypertensive drugs like “Nicorandil” require frequent dosing due to their shorter half-life. Such drugs are also pH sensitive, due to which greater portions of these drugs are degraded in acidic pH of stomach resulting in lesser bioavailability. The objective of this study was to formulate graft polymeric carrier system for sustained delivery of nicorandil to minimize dosing frequency and enhance patient compliance. Materials Methods: This animal model study was conducted in Department of Pharmacy, Islamia University of Bahawalpur, Pakistan. Hydroxypropyl methyl cellulose-graft-acrylic acid hydrogels were synthesized by free radical solution polymerization with diverse weight ratios of polymer, monomer and cross linker. Total duration of study was 1.5 years from March 2013 to August 2015. The N, N-methylene bis acrylamide and potassium persulfate were used as crosslinker and initiator respectively. Hydrogels were characterized for swelling ratio, equilibrium swelling, gel content, porosity and in vitro drug release. The surface morphology of synthesized hydrogels was evaluated by using Scanning Electron Microscopy. Thermal properties of hydrogels were evaluated by Thermogravimetric Analysis and Differential Scanning Calorimetry whereas FTIR was done to examine chemical compatibility. Finally, in vivo evaluation of prepared hydrogels was carried out in rabbits using simple parallel study design to estimate various pharmacokinetic parameters.Results: HPMC-co-AA hydrogels had good pH sensitivity whereas; they demonstrated maximum and minimum swelling at pH 7.4 and 1.2 respectively. Swelling ratio, gel fraction and cumulative percent drug release were decreased with increasing crosslinker concentration while these parameters were increased with increasing AA and HPMC concentrations. A porous network was observed in the SEM images. All formulation ingredients of prepared hydrogels showed good compatibility as determined by FTIR. Results of in vivo study proved the pH sensitivity and sustained drug release of prepared hydrogels.Conclusion: The HPMC-graft-AA hydrogels showed good pH-sensitivity and sustained-release profile for model drug nicorandil.

Biochar loaded chitosan/gelatin/poly(ethylene glycol) biocomposite beads: Morphological, thermal and swelling properties

The chitosan/gelatin/biochar biocomposite beads were prepared via the use of the emulsion crosslinking method in the presence of poly(ethylene) glycol as a cross-linker. The effects of different ratios of biochar (1 and 5%) on the characteristics of the beads were evaluated by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA) and Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR) and swelling studies. The FT-IR results showed the interactions of biochar and polymer matrix. The prepared beads showed good swelling properties and different morphologies. The average diameter of neat chitosan/gelatin beads was almost 725 µm, while the average diameter of 1% and 5% biochar incorporated beads were 726 µm and 597 µm, respectively. The swelling capacity of the beads was decreased from 4671% to 2092% when the biochar incorporation ratio increased from 1% to 5%. This indicated that the preparation of beads with varying properties can be achieved by controlling the biochar amount. The beads may be evaluated in various applications as polymeric carrier systems and adsorbents.

Synthesis of a new triple-responsive biocompatible block copolymer: Self-assembled nanoparticles as potent anticancer drug delivery vehicle

There has been a continuous effort towards a synthesis of new stimuli-responsive polymer nanoparticle systems for improved cancer chemotherapy over the last decade. In this context, we have presently developed a temperature, pH, and redox-responsive amphiphilic block-copolymer capable of forming nanoparticles in the aqueous medium, targeted towards drug delivery applications. The copper-catalyzed azide-alkyne cycloaddition reaction was utilized to tie the ends of two copolymers - a thermo-responsive poly(N-isopropylacrylamide) based copolymer with an azide end group and a pH-responsive hydrophobic polymer with redox responsive disulfide bond and an alkyne end group, producing a new triple responsive amphiphilic block copolymer (PHNP) that self-assemble in water to produce nanoparticles. Upon heating above the cloud point of poly(N-isopropylacrylamide), these nanoparticles experienced further aggregation to produce larger sized particles as measured by dynamic light scattering, UV–visible spectroscopy, and scanning electron microscopy techniques. PHNP was found to be capable of encapsulating drugs like doxorubicin (DOX) and also fluorescent probes alike Nile Red. The drug release kinetics divulged that in a period of 24 h more than 90% of the encapsulated DOX was released in pH 5.4 buffer having 10 mM glutathione (GSH) at 40 °C, an environment prevailing in cancer tissues. In vitro studies including live-dead assay and rhodamine-DAPI staining showed that PHNP was non-cytotoxic. DOX-loaded PHNP was observed to be more effective in prohibiting bone cancer cell (MG63) line in comparison to free DOX, demonstrated by the significant reduction of IC50 values. The uptake studies showed that DOX-encapsulated PHNP was more effective for morphometric distortion of MG63 cells in comparison to bare DOX. Therefore, the present research on the development of a biocompatible thermal, pH, and redox-responsive polymer opens up new opportunities in the area of polymeric carrier systems for drug delivery to cancer cells.

Surface Modification of Spider Silk Particles to Direct Biomolecular Corona Formation.

In recent years, spider silk-based materials have attracted attention because of their biocompatibility, processability, and biodegradability. For their potential use in biomaterial applications, i.e., as drug delivery systems and implant coatings for tissue regeneration, it is vital to understand the interactions between the silk biomaterial surface and the biological environment. Like most polymeric carrier systems, spider silk material surfaces can adsorb proteins when in contact with blood, resulting in the formation of a biomolecular corona. Here, we assessed the effect of surface net charge of materials made of recombinant spider silk on the biomolecular corona composition. In-depth proteomic analysis of the biomolecular corona revealed that positively charged spider silk materials surfaces interacted predominantly with fibrinogen-based proteins. This fibrinogen enrichment correlated with blood clotting observed for both positively charged spider silk films and particles. In contrast, negative surface charges prevented blood clotting. Genetic engineering allows the fine-tuning of surface properties of the spider silk particles providing a whole set of recombinant spider silk proteins with different charges or peptide tags to be used for, for example, drug delivery or cell docking, and several of these were analyzed concerning the composition of their biomolecular corona. Taken together this study demonstrates how the surface net charge of recombinant spider silk surfaces affects the composition of the biomolecular corona, which in turn affects macroscopic effects such as fibrin formation and blood clotting.

&amp;lt;i&amp;gt;In-Silico&amp;lt;/i&amp;gt; Validation and Development of Chlorogenic Acid (CGA) Loaded Polymeric Nanoparticle for Targeting Neurodegenerative Disorders

Background: Recent decades witnessed a significant growth in terms of phytocompounds based therapeutics, extensively explored for almost all types of existing disorders. They have also been widely investigated in Neurodegenerative disorders (NDDs) and Chlorogenic acid (CGA), a polyphenolic compound having potential anti-inflammatory and anti-oxidative properties, emerged as a promising compound in ameliorating NDDs. Owing to its poor stability, bioavailability and release kinetics, CGA needed a suitable nanocarrier based pharmaceutical design for targeting NDDs. Objective: The current study is aimed at the in-silico validation of CGA as an effective therapeutic agent targeting various NDDs followed by the fabrication of polymeric nanoparticles-based carrier system to overcome its pharmacological limitations and improve its stability. Methods: A successful in-silico validation using molecular docking techniques along with synthesis of CGA loaded polymeric nanoparticles (CGA-NPs) by ionic gelation method was performed. The statistical optimisation of the developed CGA-NPs was done by Box Behnken method and then the optimized formulation of CGA-NPs was characterised using particle size analysis (PSA), Transmission electron microscopy (TEM), Fourier Transform Infrared spectroscopy (FTIR) along with in-vitro release kinetics analysis. Results & Conclusion: The results attained exhibited average particle size of 101.9 ± 1.5 nm, Polydispersibility (PDI) score of 0.065 and a ZP of −17.4 mV. On a similar note, TEM results showed a size range of CGA-NPs between 90 - 110 nm with a spherical shape of NPs. Also, the data from in-vitro release kinetics showed a sustained release of CGA from the NPs following the first-order kinetics suggesting the appropriate designing of nanoformulation.

Glyceryl monooleate functionalized matrix with an inter polyelectrolyte complex system for the management of drug resistance in tuberculosis

ObjectiveInter polyelectrolyte complexes (IPECs) are an emerging biocompatible polymeric carrier system to transport active substances at target sites. The aim of this study was to evaluate the use of hydrophobic waxy retardant polymer glyceryl monooleate in hydrophilic inter polyelectrolyte matrix system containing three principal anti-tubercular drugs (ATDs). Sustained release polymeric matrix system was prepared by melt granulation technique, which allowed for the manufacture of the multi-layered tablets for segregated delivery of rifampicin, isoniazid and pyrazinamide.The matrix system consisting of hydrophilic IPEC of chitosan and carboxymethyl guar gum in combination with hydrophobic waxy retardant polymer, prepared by melt granulation technique was found to achieve segregated delivery of rifampicin, isoniazid and pyrazinamide. The applicability of piperine, an organic alkaloid as bio enhancer and rifampicin-sodium lauryl sulphate (SLS) complex was tested for improvement in bioavailability of antituberculosis fixed dose combination (FDC), lowering dosage levels and shortening the treatment course.ResultsThere was no incompatability observed between drug and excipeints based upon FTIR, DSC and X-RD studies. The optimized tablet (composition IPEC 46 % w/w (275mg), glyceryl monooleate 2 % w/w (11.5mg), piperine 1 % w/w (5 mg), pyrazinamide (150mg), isoniazid (50mg) and rifampicin-SLS complex (95.2mg) sustained the delivery of drugs for 12 h. IPECs alone lack sufficient mucoadhesion hence, suitable combination of polymeric blends along with IPEC played a key role in controlling the initial burst release pattern, desired bioadhesion (14.25g) and swelling index (1248.8%).This biocompatible, biodegradable and naturally renewable polymeric matrix system could be successfully utilized in a FDC to maximally release ATDs in a sustained manner achieving complete dissolution.

Overcoming the barrier of CD8+T cells: Two types of nano-sized carriers for siRNA transport

Bioengineering immune cells via gene therapy offers treatment opportunities for currently fatal viral infections. Also cell therapeutics offer most recently a breakthrough technology to combat cancer. These primary human cells, however, are sensitive to toxic influences, which make the utilization of optimized physical transfection techniques necessary. The otherwise commonly applied delivery agents such as LipofectamineⓇ or strongly cationic polymer structures are not only unsuitable for in vivo experiments, but are also highly toxic to immune cells. This study aimed to improve the design of polymeric carrier systems for small interfering RNA, which would allow efficient internalization into CD8+T-cells without affecting their viability and thereby removing the current limitations in the field. Here, two new carrier systems for small interfering RNA were tested. One is a cationic diblock copolymer, in which less than 10% of the monomers were modified with triphenylphosphonium cations. This moiety is lipophilic, promotes uptake and it is mostly known for its mitotropic properties. Furthermore, cationic nanohydrogel particles were synthesized in exceedingly small sizes (Rh < 14 nm). After full physicochemical characterization of the two carriers, extensive cytotoxicity studies were performed and the concentration dependent uptake into CD8+T-cells was tested in correlation to incubation time and protein content of the surrounding medium. Both carriers facilitated efficient complexation of siRNA as well as significant internalization into primary human cells in less than three hours of incubation. In addition, neither of the delivery systems reduced cell viability making them good candidates to transport siRNA into CD8+T-cells efficiently. Statement of significanceThis study provides insights into the design of polymeric delivery agents as the method of choice for overcoming the limitations of cell manipulation. Until now, CD8+T-cells, which have become a treatment tool for currently fatal diseases, have not yet been made accessible for gene silencing by polymeric siRNA carrier systems. Choosing appropriate modification approaches for two chemically different polymer structures, we were, in both cases, able to achieve significant uptake in these cells even at low concentrations and without inducing cytotoxicity. These results remove current limitations and pave the way for bioengineering via gene therapy.

A QCM-based assay of drug content in Eudragit RS 100-based delivery systems

A specific version of the quartz crystal microbalance method has been proposed for quantitative evaluation of drug content in polymeric drug carrier systems. In this study, ammonio methacrylate copolymer (type B) microparticles and their standard solutions have been prepared and loaded with set amounts of the medications diltiazem (base) and lidocaine. The analytes have been segregatim deposited on the surface of the resonator and the drug content in them has been derived from the downshift of the resonance frequency produced by irreversible interaction of the drug molecules with irradiating hydrochloric gas. The obtained results have been statistically processed on a number of samples and have been found to exhibit excellent coherence to set theoretical values. As an alternative, the conventional pharmacopoeial UV-Vis spectral method has also been separately applied to studied samples, revealing worsened performance in the case of lidocaine due to polymer matrix interference. Thus the universality of the QCM method has been proved to add to its versatility and precision. The method appears to be readily applicable to the routine pharmaceutical quantity control of bulk and multiparticulate drug forms.

Preparation and characterization of oxaliplatin drug delivery vehicle based on PEGylated half-generation PAMAM dendrimer

Dendrimers were well-known as a polymeric nanoparticle drug carrier system. Among them, polyamidoamine (PAMAM) dendrimers were firstly and systematically studied. Herein, to explore the additional modification of PAMAM for drug deliver application, this study assessed the PEGylated half-generation G3.5 to load oxaliplatin (OXA). The proton nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FTIR) spectroscopy were used to confirm the successful synthesis of G3.5, and PEGylated G3.5. PEG modification on G3.5 neutralized the negative charge of G3.5 that was confirmed by zeta potential measurement, and increased the dimension of G3.5 from 10 to 100 nm that was carried out by TEM technique. G3.5-PEG showed the high drug loading efficiency of 75.69%. The release kinetic of OXA from G3.5-PEG@OXA indicated that no burst released phenomenon occurred (11.95% within first hour) and sustainable release was achieved. In cytotoxicity test with normal cells of L929 fibroblasts, the carrier system of G3.5-PEG did not induced any cytotoxicity. To test the killing effect of G3.5-PEG@OXA on cancerous cells of human cervical cancer cells (HeLa), lung adenocarcinoma (A549), and breast cancer (MCF-7), resazurin test and live/dead staining assay was used to observe the alive cells. The increase of OXA amount in G3.5-PEG@OXA lead to decrease the cell viability from 79.90–56.97% (HeLa), 84.80–64.00% (A549), and 92.00–65.00% (MCF-7) after 48 h treatment.

Targeting Cancer with Peptide RNAi Nanoplexes.

With the recent explosion of genomic information on the root causes of disease, there is an increased interest in nucleic acid therapeutics, including siRNA and gene therapy, all of which require delivery of highly charged nucleic acids from siRNA with a molecular weight of about 1.4×104 to plasmids with an approximate molecular weight of 2.0-3.0×106. This chapter describes the delivery of shRNA via plasmid or siRNA with a peptide-based carrier. We focus on the histidine-lysine peptide which serves as an example for other peptides and polymeric carrier systems. When the HK peptide and nucleic acids are mixed together and interact with one another through ionic and nonionic interactions, nanoplexes are formed. These nanoplexes, carrying either shRNA or siRNA that target oncogenes, provide promising options for the treatment of cancer. We describe methods of preparation and characterization of these nanoplexes using dynamic light scattering, zeta potential, and gel retardation assays. We also provide protocols for transfection in vitro and in vivo for these nanoplexes.