Drug Release Time Research Articles

Machine learning predicts 3D printing performance of over 900 drug delivery systems

Three-dimensional printing (3DP) is a transformative technology that is advancing pharmaceutical research by producing personalized drug products. However, advances made via 3DP have been slow due to the lengthy trial-and-error approach in optimization. Artificial intelligence (AI) is a technology that could revolutionize pharmaceutical 3DP through analyzing large datasets. Herein, literature-mined data for developing AI machine learning (ML) models was used to predict key aspects of the 3DP formulation pipeline and in vitro dissolution properties. A total of 968 formulations were mined and assessed from 114 articles. The ML techniques explored were able to learn and provide accuracies as high as 93% for values in the filament hot melt extrusion process. In addition, ML algorithms were able to use data from the composition of the formulations with additional input features to predict the drug release of 3D printed medicines. The best prediction was obtained by an artificial neural network that was able to predict drug release times of a formulation with a mean error of ±24.29 min. In addition, the most important variables were revealed, which could be leveraged in formulation development. Thus, it was concluded that ML proved to be a suitable approach to modelling the 3D printing workflow.

3D Printed Intragastric Floating and Sustained-Release Tablets with Air Chambers

This work aimed to use hot-melt extrusion (HME) and dual fused deposition modeling (FDM) 3D printing technology to develop a novel intragastric floating and sustained-release drug delivery system. The intragastric floating and sustained-release tablet was engineered by employing hydroxypropyl methylcellulose (AffinisolTM HPMC HME 15LV) for a drug-loaded core and polylactic acid (PLA) for an insoluble shell with an air chamber. Filaments for the drug-loaded core were compounded using a single-screw hot melt extruder. 3DMAX software was utilized to design a core with a complementary shell which consisted of a hollow chamber at the top and a drug-release window with different sizes (radius in 1.5, 2.5, 3, 3.5, 4.5 mm) at the bottom. Pharmaceutical characterization, solid dispersion evaluation, and drug release behavior were studied. The model drug in all formulations kept stable, and part of the drug in the extruded filaments and 3D printed tablets became amorphous. The introduction of an air chamber reduced the tablet density to below 0.9 g/cm3 and the 3D printed tablets floated immediately and continuously during the drug release process. The presence of the insoluble shell greatly prolonged the drug release time, and the drug release rate was positively correlated with the area of the release window. In addition, compared with shellless tablets, the 3D printed tablets with air chambers (radius in 4.5 mm) showed closer zero-order drug release for 24 h and released drug by diffusion-erosion combined mechanism. The developed intragastric floating and sustained-release tablets with air chambers could be applied to various drugs and provided a new way for the development of personalized drug delivery systems.

Preparation of bio-nano bandage from quince seed mucilage/ZnO nanoparticles and its application for the treatment of burn

Burns and skin wounds require special care and treatment because the body skin is the first defense barrier against pathogens. Therefore, quick and suitable treatment of the wound is very important. Using nanotechnology, special wound dressings can be created for the all types of wounds that the time, place, and rate of drug release can be controlled. Also, nanobandages can be used as a cover for the wound to prevent of microorganisms entering to the body and creating an infection. Very fine and continuous fibers with diameters of micrometers to several nanometers range can be produced using electrospinning method and various materials such as natural and synthetic polymers. In this study, the nanoparticles of Zinc Oxide synthesized by the green method (using the walnut leaf extracts) with quince seed mucilage (as a new biopolymer)/chitosan/PEO were used for preparing antibacterial nanobandages. The best fibers with suitable diameters, shape and appropriate loading of ZnO nanoparticles were obtained in the ratio of 20: 80 quince seed mucilage to chitosan/PEO. Best effective parameters in the electrospinning were obtained as follows: voltage = 18 kV, feed rate of polymer solution 1 mL/h and Needle-to-collector distance 12 cm. The produced nanofibers were characterized by FT-IR spectroscopy, X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM) and tensile test. The results of animal test showed that nanobandage containing ZnO nanoparticles had a significant treatment effect on grade 2 burn wounds and the burn healed more quickly and no infections were detected in the wound. After 21 day the skin was completely restored and there was no evidence of burns on their bodies. The results showed that the effect of developed nanobandage on wound healing was much greater than the nanobandage without nanoparticles and control.

Formulation and Evaluation of Dispersible tablets of a Model Anti-Parasitic Drug

The study was aimed to formulate and evaluate dispersible tablets of a model anti-parasitic drug (XXX) with an objective to produce fast dispersion of tablets by reducing the disintegration time using three superdisintegrants like Sodium Starch Glycolate (SSG), Crospovidone (PVP K30) and Croscarmellose sodium (CCS) and also diluents namely MCC and Lactose by changing their concentrations in each formulations. Totally six formulations (F1-F6) were prepared by direct compression method and evaluated for hardness, thickness, weight variation, friability, wetting volume, wetting time, water absorption ratio, uniformity of dispersion, in-vitro disintegration time, Drug content, in-vitro dissolution test and release kinetics study. FTIR studies was carried out to see possible drug excipients interaction. The stability studies were performed as per ICH guidelines. Among the formulations F6 formulation was found to be promising as it showed better results than other five formulations with In-vitro disintegration time, percentage drug release and dispersion time of 16 ± 0.93 seconds, 98.32±0.54% and 66±1.30 seconds respectively. Further the FTIR results revealed that there was no interactionF between drug and excipients. Stability study of formulation showed no significant changes in tablet properties and the drug follows Higuchi release kinetics with Fickian diffusion mechanism.

Nanoemulgel for Improved Topical Delivery of Desonide: Formulation Design and Characterization.

This research aimed to develop a novel drug delivery system to improve treatment of skin disorders. The system is comprised of a Carbopol 980-based nanoemulgel (NE-gel) containing a desonide (DES; 0.05%, w/w) nanoemulsion (NE), which has a small particle size, high encapsulation efficiency, good thermodynamic stability, good permeation ability, and high skin retention. DES-loaded NE (DES-NE) was prepared by high-pressure homogenization. The developed formulation was characterized by differential scanning calorimetry (DSC), X-ray diffraction, drug release, skin permeation, and drug retention. DES in vitro release and skin permeation studies with different formulations of artificial membrane and rat abdominal skin were performed with the Franz diffusion cell system. Confocal laser scanning microscopy(CLSM) was used to detect the localization and permeation pathways of drugs in the skin. Compared with commercially available gel (CA-gel) and NE, the NE-gel release process conformed to the Higuchi release model (R2 = 0.9813). NE-gel prolonged the drug release time and allowed for reduced administration dose and frequency. The unit cumulative permeation of NE and NE-gel through the skin for 12 h was 63.13 ± 2.78 and 42.53 ± 2.06 μg/cm2, respectively, values significantly higher (p < 0.01) than that of the CA-gel (30.65 ± 1.25 μg/cm2) and CA-cream (15.21 ± 0.97 μg/cm2). The DES-NE and DES NE-gel skin drug retention was significantly higher than commercially available formulations (p < 0.01). Hence, the prepared NE-gel is a potential vehicle for improved topical DES delivery for better treatment of skin disorders.

Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Hollow organic/inorganic hybrid nanoparticles from dextran-block-polypeptide copolymer: Double click reaction synthesis and properties

To increase the drug loading and prolong the drug release time, novel hollow organic/inorganic hybrid nanoparticles based on dextran-b-poly(L-glutamate-graft-3-mercaptopropyltrimethoxysilane) (Dex-b-P(ALG-g-MTPMS)) were prepared. First, a polysaccharide block polypeptide diblock copolymer, dextran-block-poly(γ-allyl-L-glutamate) (Dex-b-PALG) bearing allyl side-groups, has been synthesized by the combination of ring-opening polymerization and alkyne-azide [2 + 3] Huisgen's cycloaddition. Next, the allyl side-groups residing in the poly(γ-allyl-L-glutamate) block were further functionalized with 3-mercaptopropyltrimethoxysilane(MPTMS) by radical “thiol-ene” addition reactions. Finally, after a sol-gel process of the obtained copolymers, the novel organic/inorganic hybrid nanoparticles were prepared. The molecular structures, physicochemical, and self-assembly of these copolymers were characterized through FTIR, 1H NMR, dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The cross-linked hybrid nanoparticles have a higher drug loading ability and slower release rate as compared to the uncross-linked counterparts. The MTT evaluation demonstrated that the organic/inorganic hybrid nanoparticles with good biocompatibility.

RGD Peptide‐Drug Conjugates as Effective Dual Targeting Platforms: Recent Advances

AbstractIn recent years, targeted therapies have raised increasing interest as effective strategies to improve therapeutic efficiency, reduce the impact of adverse side effects, and overcome drug resistance, particularly in the field of cancer chemotherapeutics. Many examples of RGD (Arg‐Gly‐Asp) peptide‐drug conjugates (PDCs) have been proposed as targeted drug delivery systems. These molecular hybrids embody high affinity ligands targeting disease signatures (overexpressed integrin receptors or specific integrin‐related pathways within diseased cells/tissues) connected to recognized therapeutic units by means of carefully designed linker‐spacer combinations, to ultimately control stability, physico‐chemical properties, timing, and localization of drug release. This account has collected and critically surveyed relevant contributions from the period of 2015 to the present day, wishing to provide a window open on new synthesis strategies facing the challenging issues of site‐selective drug delivery and dual drug targeting.

Rifapentine Polylactic Acid Sustained-Release Microsphere Complex for Spinal Tuberculosis Therapy: Preparation, in vitro and in vivo Studies

PurposeSpinal tuberculosis has been a common clinical extrapulmonary tuberculosis in recent years. The general anti-tuberculosis drug treatment cycle is long, with unsatisfactory efficacy. This study focused on the preparation and evaluation of rifapentine polylactic acid sustained-release microsphere complex for spinal tuberculosis therapy.MethodsRifapentine polylactic acid sustained-release microspheres (RPSMs) were prepared through the double emulsion solvent evaporation method, and RPSMs were combined with hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) composite material to obtain drug-loaded, sustained-release complex. We evaluated the complex for dynamics of drug release and osteogenic ability using in vitro release test, alkaline phosphatase and alizarin red staining, real-time PCR and Western blot. A rabbit model of a spinal tuberculosis defect was established and repaired using HA/β-TCP or complex. The ability of anti-tuberculosis and tissue repair effects of the complex were evaluated through in vivo experiments.ResultsThe complex constructed of RPSMs and HA/β-TCP demonstrated a long drug release time, with no significant inhibition of cell osteogenic differentiation in vitro experiments. Postoperative macroscopic observation, immunohistochemical staining and Nilsson histological scores showed that the complex has good effects on the tissue repair. Moreover, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), important indexes of inflammation, decreased to normal levels in the complex group.ConclusionIn vitro and in vivo experiments demonstrated that the complex constructed of RPSMs and HA/β-TCP effectively treated spinal tuberculosis. Therefore, the complex represents a promising approach for the treatment of spinal tuberculosis.

Mesoporous Silica-Bioglass Composite Pellets as Bone Drug Delivery System with Mineralization Potential.

For decades, local bone drug delivery systems have been investigated in terms of their application in regenerative medicine. Among them, inorganic polymers based on amorphous silica have been widely explored. In this work, we combined two types of amorphous silica: bioglass and doxycycline-loaded mesoporous silica MCM-41 into the form of spherical granules (pellets) as a bifunctional bone drug delivery system. Both types of silica were obtained in a sol-gel method. The drug adsorption onto the MCM-41 was performed via adsorption from concentrated doxycycline hydrochloride solution. Pellets were obtained on a laboratory scale using the wet granulation-extrusion-spheronization method and investigated in terms of physical properties, drug release, antimicrobial activity against Staphylococcus aureus, mineralization properties in simulated body fluid, and cytotoxicity towards human osteoblasts. The obtained pellets were characterized by satisfactory mechanical properties which eliminated the risk of pellets cracking during further investigations. The biphasic drug release from pellets was observed: burst stage (44% of adsorbed drug released within the first day) followed by prolonged release with zero-order kinetics (estimated time of complete drug release was 19 days) with maintained antimicrobial activity. The progressive biomimetic apatite formation on the surface of the pellets was observed. No cytotoxic effect of pellets towards human osteoblasts was noticed.

Multi-step cefazolin sodium release from bioactive TiO2 nanotubes: Surface and polymer coverage effects

Bacterial implant-related infections have been pointed out as the leading cause of metal implant failure. Recently, nanotexturization of biomaterials surface associated with antibiotic loading revealed itself as a promising strategy for enhancing osseointegration while mitigating bacterial infections. However, fewer studies describe the effects of multi-step local drug delivery. This study investigates 1 mg Cefazolin Sodium (CS) release from anodic nanotextured titanium-based devices and the effect of polymer coverage with differential aqua solubility characteristics (Chitosan—CH and Carboxymethylcellulose—CM). Results show that larger inner pore diameters are related to longer drug release times on uncovered samples. The polymeric coverage decreases the release rates, highlighting the Carboxymethylcellulose boosting the Cefazolin release time by 51–77 fold. All biomaterials exhibited a low or absent hemolytic activity and considerable bacteria inactivation. In summary, 40 °C/CM-based samples present the most promising results for drug release devices.

Electrospun Aspirin/Eudragit/Lipid Hybrid Nanofibers for Colon-targeted Delivery Using an Energy-saving Process.

Both electrospinning apparatus and their commercial products are extending their applications in a wide variety of fields. However, very limited reports can be found about how to implement an energy-saving process and in turn to reduce the production cost. In this paper, a brand-new type of coaxial spinneret with a solid core and its electrospinning methods are developed. A novel sort of medicated Eudragit/lipid hybrid nanofibers are generated for providing a colon-targeted sustained release of aspirin. A series of characterizations demonstrates that the as-prepared hybrid nanofibers have a fine linear morphology with the aspirin/lipid separated from the matrix Eudragit to form many tiny islands. In vitro dissolution tests exhibit that the hybrid nanofibers are able to effectively prevent the release of aspirin under an acid condition (8.7%±3.4% for the first two hours), whereas prolong the drug release time period under a neutral condition(99.7±4.2% at the seventh hour). The energy-saving mechanism is discussed in detail. The prepared aspirin-loaded hybrid nanofibers can be further transferred into an oral dosage form for potential application in countering COVID-19 in the future.

Electrospun PVP/PVA Nanofiber Mat as a Novel Potential Transdermal Drug-Delivery System for Buprenorphine: A Solution Needed for Pain Management

Over the past several decades, the formulation of novel nanofiber-based drug-delivery systems has been a frequent focus of scientists around the world. Aiming to introduce a novel nanofibrous transdermal drug-delivery system to treat pain, the nanofiber mats of buprenorphine-loaded poly (vinyl pyrrolidone) (Bup/PVP) and buprenorphine-loaded poly(vinyl alcohol)/poly(vinyl pyrrolidone) (Bup/PVP/PVA) were successfully fabricated by the electrospinning process for transdermal drug delivery. Similarly, PVP and PVP/PVA nanofibers were fabricated in the same conditions for comparison. The viscosity and electrical conductivity of all electrospinning solutions were measured, and nanofiber mats were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared (FT-IR) spectroscopy and contact angle analysis. The conductivity of PVP and PVP/PVA solutions showed a considerable increase by the addition of buprenorphine due to the polarity of buprenorphine. SEM images showed a smooth, fine and porous nanofibrous structure without any adhesion or knot for all of the samples. The contact angle analysis showed the increased hydrophilicity and wettability of PVP/PVA and Bup/PVP/PVA nanofibers compared to PVP and Bup/PVP nanofibers which can be attributed to the addition of PVA. Attenuated total reflectance (ATR) FT-IR results confirmed that the electrospinning process did not affect the chemical integrity of the drug. For the modification of the drug release rate, the cross-linking of nanofiber mats was carried out using glutaraldehyde. Drug release measurements using high-performance liquid chromatography (HPLC) analysis demonstrated that Bup/PVP/PVA nanofibers exhibited better physical and chemical properties compared to Bup/PVP. Furthermore, the cross-linking of nanofibers led to an increase in drug release time. Thus, the novel buprenorphine-loaded nanofibers can be efficient biomaterial patches for transdermal delivery against pain improving carrier retention and providing a controlled release of the drug.

Expandable, dual-excipient fibrous dosage forms for prolonged delivery of sparingly-soluble drugs

In this work, expandable fibrous dosage forms containing water-absorbing and fiber-strengthening excipients are investigated for prolonged delivery of sparingly-soluble drugs. The formulation comprised: sparingly-soluble ibuprofen drug; water-absorbing, high-molecular-weight hydroxypropyl methylcellulose (HPMC) excipient; and strengthening methacrylic acid-ethyl acrylate excipient. Upon immersion in a dissolution fluid, the single fibers and all the dosage forms (fiber volume fractions, φ = 0.16, 0.39, and 0.56) expanded roughly at the same rate. The size of the dosage forms doubled in fifteen minutes, and they were converted into a highly viscous gel. The gel was stabilized by the strengthening excipient for over two days. Eighty percent of the drug was released from single fibers in less than an hour, and in thirty-eight hours from the dosage form with φ = 0.56. Theoretical models suggest that if φ is small, drug release is limited by the diffusion of drug molecules through the thin fibers, which is fast. If φ is large, however, drug release is limited by the diffusion of drug molecules through the thick, monolithic dosage form gel, which is slow. Between these extremes, the drug release time increases exponentially with φ.

Loading of Propranolol Hydrochloride on MCF and Sustained Release

Aims: Adsorption conditions of propranolol hydrochloride onto MCF are optimized. Properties of this adsorption system are studied. The sustained release properties of propranolol hydrochloride in the loading system are also researched. Background: In today's society, demand for drugs is getting higher and higher. With the development of nanotechnology, it is easier to immobilize drugs on nanomaterials, which can easily transport drugs in the human body. It can control drug release, reduce side effects, improve drug efficacy, and develop drug orientation. Objective: The purpose of this study was to load propranolol hydrochloride, a drug for the treatment of heart disease and hypertension on the MCF nano-mesoporous material to prepare a sustainedrelease preparation and investigate the release law of propranolol hydrochloride in simulated human body fluid. Methods: Nanometer mesoporous MCF (mesocellular foams) silica material was prepared in acidic medium using triblock copolymer poly(ethylene glycol)-block-poly(propyl glycol)-block-poly(ethylene glycol) as template and tetraethoxysilane as silica source. Propranolol hydrochloride drug was incorporated into the MCF mesoporous material by the impregnation method to prepare MCF-propranol hydrochloride host-guest composite material. The loading amount of drug was calculated by spectrophotometry and difference subtraction method. Results: The loading amount of drug calculated by spectrophotometry and difference subtraction method was 385.5 mg·g-1 (propranolol hydrochloride/MCF). The adsorption process of propranolol hydrochloride in MCF belongs to the quasi-second-order kinetic process. Adsorption process ΔH0 = -19.11 kJ·mol-1, is an exothermic process, ΔG0 &lt; 0, the adsorption process is a spontaneous process. The effective release time of drug lasted up to 32 h and the maximum cumulative released amount was 99.4 % through the experiment of drug sustained release in the simulated body fluid. In the simulated gastric juice, the release time of drug reached 6 h, and the maximum cumulative released amount was 56.6 %. When drug release time arrived at 10 h in the simulated intestinal fluid, the maximum cumulative released amount was 71.3 %. Conclusions: The influence of the release rate of propranolol hydrochloride molecules from MCF mesopores was demonstrated, since it results in a very slow drug delivery from the nanocomposite system. Thus, it is concluded that the prepared MCF is an efficient drug sustained-released carrier.

To control floating drug delivery system in a simulated gastric environment by adjusting the Shell layer formulation

BackgroundGastroretentive drug delivery system (GDDS) are novel systems that have been recently developed for treating stomach diseases. The key function of all GDDS systems is to control the retention time in the stomach. However, research into the bulk density or entanglement of polymers, especially regarding their effects on drug float and release times, is scarce.MethodsIn this research, we prepared the floating core-shell beads carrying tetracycline. The ratio of chitosan and xanthan gum in the shell layer was changed to modify polymer compactness. Tetracycline was encapsulated in the alginate core.ResultsUsing scanning electron microscopy (SEM) techniques, we observed that the shell formulation did not change the bead morphology. The cross-sectional images showed that the beads were highly porous. The interaction between anionic xanthan gum and cationic chitosan made the shell layer dense, resisting to the mass transfer in the shell layer. Due to the high mass transfer resistance to water penetration, the longer float and delivery time were caused by the dense surface of the beads. The cell culture demonstrated that floating core-shell beads were biocompatible. Importantly, the beads with tetracycline showed a significant prolonged anti-bacterial effect.ConclusionResearch results proved that the floating and releasing progress of core-shell beads can be well controlled by adjusting the shell layer formulation that could promote the function of gastroretentive drugs.

Synthesis and characterization of an injectable microparticles integrated hydrogel composite biomaterial: In-vivo biocompatibility and inflammatory arthritis treatment

Polymeric hydrogels and microparticles have been widely used for localized drug delivery applications for the treatment of arthritis. Nonetheless, owing to initial burst drug release, non-specific biodistribution and low retention time at the target site in body, these polymeric drug delivery systems have been found with low in-vivo performance. Hence, the above limitations need to be resolved by designing a smart novel drug delivery system which is the current need in biomedicine. Herein, a novel localized injectable thermoresponsive microparticles embedded hydrogel composite drug delivery system has been developed for the treatment of inflammatory arthritis. In the current study, methotrexate (MTX) loaded alginate microparticles (MTX-Microparticles) are embedded into thermoreversible hydrogel matrix (MTX-MPs-H) prepared by physical blending of sodium hyaluronate and methylcellulose (SHMC). Microparticles-hydrogel composite system exhibited appropriate in-vitro thermoreversibility (sol at 4 °C and gel at 37 °C), biocompatibility (>80 %), hemocompatibility, and controlled drug release profile. The in-vivo biocompatibility studies for 10 days revealed that composite system is non-toxic in nature. The developed MTX-MPs-H composite drug delivery system effectively decreased the swelling/ inflammation of the arthritis affected paw in wistar rats in comparison to only alginate microparticles and pure MTX up to 30 days.

Central Composite Design for the Development and Evaluation of Floating-mucoadhesive Tablets of Gliclazide

Background: Gliclazide assimilation rate from the gastrointestinal (GI) tract is slow and inconstant, which may be either due to poor dissolution or poor permeability of the drug across the GI membrane. Objective: The present investigation deals with the formulation of floating-mucoadhesive tablets of gliclazide for oral administration using the central composite design by direct compression technique, using HPMC K4M and Carbopol 934 as release controlling polymers and sodium bicarbonate as an effervescent agent. Methods: Central composite design was employed to quantify the effect of three factorsconcentration of HPMC K4M (X1), the concentration of Carbopol 934 (X2), and concentration of sodium bicarbonate (X3) on floating lag time, drug release and mucoadhesive time of the formulation. Results: The results revealed that floating lag time decreases with a rise in the concentration of sodium bicarbonate, drug release was highest at low levels of HPMC and Carbopol and mucoadhesive time was highest at a high level of Carbopol. Conclusion: The optimized batch (F-7) shows a mucoadhesive time of 23 minutes 27 seconds, floating lag time of 22 seconds and in vitro cumulative percentage of drug release 86.73 % in 10h. From the investigation, it can be summarized that the gastro-retentive drug delivery can be utilized to enhance bioavailability and gastric residence time of the drugs.

Improved Pharmacodynamic Potential of Rosuvastatin by Self-Nanoemulsifying Drug Delivery System: An in vitro and in vivo Evaluation.

PurposeThe purpose of this proposed research was to investigate a nano-formulation developed using self-nanoemulsifying drug delivery system (SNEDDS) to improve the pharmacodynamic potential of rosuvastatin by assisting its transportation through lymphatic circulation.MethodsThe utilized lipids, surfactants, and co-surfactants for SNEDDS were selected on the basis of solubility studies. The SNEDDS formulation was optimized by implementing a D-optimal mixture design, wherein the effect of concentration of Capmul MCM EP (X1), Tween 20 (X2) and Transcutol P (X3) as independent variables was studied on droplet size (Y1), % cumulative drug release (Y2) and self-emulsification time (Y3) as dependent variables. The optimized formulation was evaluated via in vitro parameters and in vivo pharmacodynamic potential in Wistar rats.ResultsThe D-optimal mixture design and subsequent ANOVA application resulted in the assortment of the optimized SNEDDS formulation that exhibited a droplet size of nano range (14.91nm), in vitro drug release of >90% within 30 minutes, and self-emulsification time of 16 seconds. The in vivo pharmacodynamic study carried out using Wistar rats confirmed the better antihyperlipidemic potential of developed formulation in normalizing the lipidic level of serum in contrast to pure drug and marketed tablets.ConclusionThis research reports the application of D-optimal mixture design for successful and systematic development of rosuvastatin-loaded SNEDDS with distinctly enhanced in vitro and in vivo performance in comparison to marketed formulation. Eventually, improved anti-hyperlipidemic efficacy was envisaged which might be attributed to increased drug solubility and absorption. Overall, this study shows the utility of SNEDDS for improving the dissolution rate and bioavailability of poor aqueous-soluble drugs. The present SNEDDS formulation could be a promising approach and alternative to conventional dosage form.

Synthesis and cytotoxicity evaluation of gemcitabine-tobacco mosaic virus conjugates

Gemcitabine is one of the nucleoside analogue drugs that acts against a wide range of solid tumors such as pancreatic, non-small lung, breast, and ovarian cancers. Unfortunately, gemcitabine possesses rapid body clearance that limits its efficacy. This drawback is due to kidney excretion and metabolism by plasmatic enzyme cytidine-deaminase, which yields an inactive metabolite. Plant virus nanoparticles are one of the biggest groups of natural nanoparticles, which are less likely to interact with mammalian system to make adverse effects and can be used in drug delivery. In this study, chemical conjugation of gemcitabine and Tobacco Mosaic Virus (TMV); as one of the mostly used plant viruses, has been investigated through the creation of amide bond and the percentage of conjugation was calculated using UV spectroscopy. The drug release from conjugate was pH-dependent and, at acidic pH, the drug release was almost complete. The hemolysis percentage caused by the virus and the conjugate was also proved to be very small. Cytotoxicity studies at 24 and 48-h showed that there was no significant difference between the free drug and drug conjugate in HepG2 and MCF7 cell lines, but the results of the toxicity study were better on HepG2 cell line. Also in both cell lines, the observed cytotoxicity of the conjugate was more acceptable after 48 h which is due to enough time for drug release. It is expected that these viral nanoparticles make better in vivo drug delivery, pharmacokinetics improvement and reduced dose related toxicity of chemotherapeutic agents.