Burst Release Of Drug Research Articles

Comparative Pharmacokinetic Studies of One‐Month Donepezil IM Depot and Once Daily Oral Tablet in Healthy Male Volunteers

AbstractBackgroundThis study is to evaluate the safety and tolerability of single dose of one‐month donepezil IM depot (GB‐5001) in healthy male volunteers and to compare pharmacokinetic parameters of 70mg donepezil IM depot and 10mg once daily oral tablet (Aricept®) in human.MethodIn this phase 1, a randomized, double‐blind, placebo‐controlled, dose‐escalation study, 48 healthy subjects were randomized to single dose of Aricept tablet or placebo or GB‐5001 (70mg or 140mg or 280mg) for 64 days. In this study, safety and tolerability of 70mg donepezil IM depot were examined by monitoring adverse events and vital signs. PK parameters such as AUCt, AUCinf, Cmax and Tmax were compared by measuring donepezil concentration after a single dose of 70mg IM depot and 10mg oral tablet.ResultA single dose of 70mg donepezil IM depot showed no significant adverse events and was well tolerated in healthy male volunteers. In 70mg GB‐5001, all the subjects had measurable concentrations up to 1512 h post dose. The geometric mean of PK exposure parameters are 6482.82 h*ng/mL, 6604.01 h*ng/mL and 11.40 ng/mL for AUCt(0‐1512h), AUCinf, and Cmax, respectively. The median peak concentration (Tmax) was observed at 432h post dose. In 10mg oral Aricept, all the subjects had measurable concentrations up to 240 h post dose. The geometric mean of PK exposure parameters are 656.84 h*ng/mL, 751.34 h*ng/mL and 17.68 ng/mL for AUCt(0‐240h), AUCinf, and Cmax, respectively. The median peak concentration (Tmax) was observed at 2.25 h post dose.ConclusionA single dose of 70mg donepezil IM depot was found to be safe and well tolerated in healthy male volunteers. The pharmacokinetic results of 70mg donepezil IM depot showed stable donepezil blood concentration for more than one month without burst drug release, and showed comparable unit dose drug exposure not lower than that of once daily 10mg oral formulation. Through the PK results for additional higher doses and multiple PK simulations, optimal once monthly dose of donepezil IM depot could be suggested which will be bioequivalent to 10mg once daily tablet.

Phase Transition Behaviors of Poly(N-isopropylacrylamide) Nanogels with Different Compositions Induced by (−)-Epigallocatechin-3-gallate and Ethyl Gallate

Phase transition behaviors of poly(N-isopropylacrylamide) nanogels with different compositions induced by (−)-epigallocatechin-3-gallate (EGCG) and ethyl gallate (EG) has been investigated systematically. Monodisperse poly(N-isopropylacrylamide-co-N-hydroxymethyl acrylamide) (P(NIPAM-co-NMAM)) and poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (P(NIPAM-co-HEMA)) nanogels with different feeding monomer ratios were prepared by emulsion polymerization. P(NIPAM-co-NMAM) nanogels exhibit rapid isothermal phase transition behavior in EGCG solutions with low concentration (10−3 mol/L) in less than 10 minutes. The thermosensitive phase transition behaviors of nanogels are affected not only by the copolymerized monomers but also by the concentrations of EGCG and EG in aqueous solutions. Nanogels remain in a shrunken state and do not exhibit thermosensitive phase transition behaviors in EGCG solutions (≥5 mmol/L), whereas they display thermo-responsive phase transition behaviors in EG solutions. The volume phase transition temperature (VPTT) shifts to lower temperatures with increasing EG concentration. The diameters of P(NIPAM-co-NMAM) nanogels decrease with increasing EG concentration at temperatures between 29 and 33 °C. In contrast, the diameters of P(NIPAM-co-HEMA) nanogels increase with increasing EGCG concentration at temperatures between 37 and 45 °C. The results demonstrate the potential of nanogels for simple detection of EG and EGCG concentrations in aqueous solutions over a wide temperature range, and EGCG can serve as a signal for the burst-release of drugs from the P(NIPAM-co-NMAM)-based carriers at physiological temperature.

Formulation of chitosan based lipid polymer hybrid nanocarrier system for oral delivery of tamoxifen citrate: Toxicological and hemocompatibility evaluation

The objective of the current work was to develop chitosan based lipid nanocarriers for the oral controlled release of tamoxifen citrate (TC). The ionic gelation method was used to develop various formulations with altered ratios of polymer, lipid, and emulsifier. The developed lipid hybrid nanoparticles (LHNPs) were characterized for particle size, polydispersity index, zeta potential, entrapment efficiency, SEM, DSC, FTIR, PXRD, in vitro release studies, stability studies, kinetic modeling, toxicity studies, and hemocompatibility assay. Particle size and entrapment efficiency of the developed formulations varied between 138.2 ± 4.2 nm to 281.8 ± 63.1 nm and 70.94 ± 0.29 % to 82.23 ± 0.02 %, respectively. The polydispersity index and zeta potential ranged from 0.199 ± 0.03 to 0.555 ± 0.01 and 17.9 ± 0.62 to 32.3 ± 0.36, respectively. Nano-sized, spherical in shape surfaces of developed particles were depicted by SEM. While removal of TC melting endotherm revealed by DSC analysis, suggested good thermal stability of LHNPs. FTIR verified that the components of the formulation do not interact chemically. PXRD depicted that the developed formulation has been successfully amorphized. In vitro release study revealed drug release, an initial burst drug release followed by the controlled release up to 72 h. Kinetic modeling exposed that all developed formulations showed a non-Fickian diffusion profile and were best fitted into Higuchi's square root and Korsmeyer-Peppas models. Toxicity investigations on female albino rabbits provided evidence for the compatibility and non-toxicity of developed particles with biological systems. Hemocompatibility assay showed that the developed system is compatible with blood and nontoxic. These investigations demonstrate the potential of developed LHNPs as a vehicle, aimed at controlled oral delivery of TC for better therapeutic applications in breast cancer.

Contact Lens with pH Sensitivity for On-Demand Drug Release in Wearing Situation.

Drug-releasing contact lenses are emerging therapeutic systems for treating ocular diseases. However, their applicability is limited by the burst release of drugs during lens wear and premature drug leakage during packaging, rendering the precise control of release duration or dose difficult. Here, we introduce a pH-sensitive contact lens exhibiting on-demand drug release only during lens wear and negligible premature drug leakage during packaging and transportation, which is accomplished by incorporating drug-loaded mesoporous silica nanoparticles (MSNs) coated with a pH-sensitive polymer into the contact lens. The compositionally optimized pH-sensitive polymer has a lower critical solution temperature (LCST) at >45 °C at pH 7.4, whereas its LCST decreases to <35 °C under acidic conditions (pH ∼ 6.5). Consequently, the MSN-incorporated contact lens sustainably releases the loaded drugs only in the acidic state at 35 °C, which corresponds to lens-wear conditions, through the MSN pores that open because of the shrinkage of polymer chains. Conversely, negligible drug leakage is observed from the contact lens under low-temperature or neutral-pH conditions corresponding to packaging and transportation. Furthermore, compared with the plain contact lens, the pH-sensitive contact lens exhibits good biocompatibility and unchanged bulk characteristics, such as optical (transmittance in the visible-light region), mechanical (elastic modulus and tensile strength), and physical (surface roughness, oxygen permeability, and water content) properties. These findings suggest that the pH-sensitive contact lens can be potentially applied in ocular disease treatment.

Advances in Therapeutic Contact Lenses for the Management of Different Ocular Conditions.

In the advent of an increasingly aging population and due to the popularity of electronic devices, ocular conditions have become more prevalent. In the world of medicine, accomplishing eye medication administration has always been a difficult task. Despite the fact that there are many commercial eye drops, most of them have important limitations, due to quick clearance mechanisms and ocular barrers. One solution with tremendous potential is the contact lens used as a medication delivery vehicle to bypass this constraint. Therapeutic contact lenses for ocular medication delivery have attracted a lot of attention because they have the potential to improve ocular bioavailability and patient compliance, both with minimal side effects. However, it is essential not to compromise essential features such as water content, optical transparency, and modulus to attain positive in vitro and in vivo outcomes with respect to a sustained drug delivery profile from impregnated contact lenses. Aside from difficulties like drug stability and burst release, the changing of lens physico-chemical features caused by therapeutic or non-therapeutic components can limit the commercialization potential of pharmaceutical-loaded lenses. Research has progressed towards bioinspired techniques and smart materials, to improve the efficacy of drug-eluting contact lenses. The bioinspired method uses polymeric materials, and a specialized molecule-recognition technique called molecular imprinting or a stimuli-responsive system to improve biocompatibility and support the drug delivery efficacy of drug-eluting contact lenses. This review encompasses strategies of material design, lens manufacturing and drug impregnation under the current auspices of ophthalmic therapies and projects an outlook onto future opportunities in the field of eye condition management by means of an active principle-eluting contact lens.

Synthesis and characterization of mesoporous bioactive glass nanoparticles loaded with peganum harmala for bone tissue engineering

Globally, there is an increase in a number of bone disorders including osteoarthritis (OA), osteomyelitis, bone cancer, and etc., which has led to a demand for bone tissue regeneration. In order to take use of the osteogenic potential of natural herbs, mesoporous bioactive glass nanoparticles (MBGNs) have the ability to deliver therapeutically active chemicals locally. MBGNs influence bioactivity and osteointegration of materials making them suitable for bone tissue engineering (BTE). In the present study, we developed Peganum Harmala (P. harmala) loaded MBGNs (PH-MBGNs) synthesized via modified Stöber process. The MBGNs were analyzed in terms of surface morphology, chemical make-up, amorphous nature, chemical interaction, pore size, and surface area before and after loading with P. harmala. A burst release of drug from PH-MBGNs was observed within 8 h immersion in phosphate buffer saline (PBS). PH-MBGNs effectively prevented Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) from spreading. Furthermore, PH-MBGNs developed a hydroxyapatite (HA) layer in the presence of simulated body fluid (SBF) after 21 days, which confirmed the in-vitro bioactivity of MBGNs. In conclusion, PH-MBGNs synthesized in this work are potential candidate for scaffolding or a constituent in the coatings for BTE applications.

Natural Polysaccharide Delivery Platforms with Multiscale Structure Used for Cancer Chemoimmunotherapy.

Chemoimmunotherapy is an effective cancer treatment method. Drugs are always combined and used in treating cancer. However, the characteristic of drugs varies, making it challenging to control their release kinetics utilizing delivery devices with a single microstructure. In this study, we attempted to uniformly size drugs of varying molecular weights and confine them in a compartment where immune cells may be recruited and moved freely. Dextran microgels were created as modular drug libraries to address the cryogel burst release of small molecule drugs. Then, modular drug libraries and granulocyte-macrophage colony-stimulating factor (GM-CSF) were integrated into cryogels for a combined treatment. Herein, alginate was zwitterion modified to avoid the immune reaction generated by the material. Because of its macroporous structure, the cryogel could be injected into the body, eliminating invasive surgical procedures. Results demonstrated that multiscale delivery platforms could improve the synergistic effect of various medications on tumor treatment.

Electrical properties of biodegradable chitosan-calcium phosphate nerve conduits doped with inorganic nanoparticles

Biodegradable nerve conductors are based on chitosan-calcium phosphate (CS/CaP) doped with nanoparticles of multiwalled carbon nanotubes (MWCNT+Fe), graphene oxide (GO), magnetite (Fe3O4) of various nanoparticle concentrations (NpC). Drug release and electrical properties were studied depending on the polarity, voltage, and electrode configuration (in-in, in-out), which reflect nerve regeneration inside the conduit and external electrical stimulation. The NpC of 150 μg/ml provides the highest electrical conductivity (EC) of 150MWCNT+Fe in-in. 150GO is more effective in the in-out configuration. The 300GO sample has an in-out electrical conductivity of 0.71∙ 10−2 S/cm, which is close to the natural nerve conductivity of 2.35∙10−2 S/cm. Nanoparticles in the CS/CaP matrix when interacting with the physiological solution ions can create new mechanisms for the current passage or neutralize existing ones. All samples are characterized by the absence of "burst drug release". Pregabalin (PG) release from Fe-containing samples is controlled by diffusion (first-order model), and from GO-containing – by diffusion and degradation of the matrix (second-order model).

Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized by Polycationic Complexation

Carfilzomib (CFZ) is a second-generation proteasome inhibitor showing great efficacy in multiple myeloma treatment, yet its clinical applications for other diseases such as solid cancers are limited due to low aqueous solubility and poor biostability. Ternary polypeptide nanoparticles (tPNPs) are drug carriers that we previously reported to overcome these pharmaceutical limitations by entrapping CFZ in the core of the nanoparticles and protecting the drugs from degradation in biological media. However, preclinical studies revealed that tPNPs would require further improvement in particle stability to suppress initial burst drug release and thus achieve prolonged inhibition of proteasome activity with CFZ against tumor cells in vivo. In this study, CFZ-loaded tPNPs are stabilized by polycations which have varying pKa values and thus differently modulate nanoparticle stability in response to solution pH. Through polyion complexation, the polycations appeared to stabilize the core of tPNPs entrapping CFZ-cyclodextrin inclusion complexes while allowing for uniform particle size before and after freeze drying. Interestingly, CFZ-loaded tPNPs (CFZ/tPNPs) showed pH-dependent drug release kinetics, which accelerated CFZ release as solution acidity increased (pH < 6) without compromising particle stability at the physiological condition (pH 7.4). In vitro cytotoxicity and proteasome activity assays confirmed that tPNPs stabilized with cationic polymers improved bioactivity of CFZ against CFZ-resistant cancer cells, which would be greatly beneficial in combination with pH-dependent drug release for treatment of solid cancers with drug resistance and tumor microenvironment acidosis by using CFZ and other proteasome inhibitors.

Utilization of pectin as a polysaccharide microcarrier for drug delivery

Pectin is a polysaccharide of natural origin, which has been widely exploited in the food and pharmaceutical industry due to its biodegradable and biocompatible nature. It is commonly used as an efficient texturizer and stabilizer in different food products due to its high stability and also as a pharmaceutical excipient in various drug formulations due to its valuable characteristics. The utilization of pectin as a drug carrier for achieving controlled drug release in pharmaceutical dosage forms has been extensively researched recently. Pectin has the potential for targeted drug delivery due to its degradation by colonic microorganisms, making it a popular subject of investigation for biomedical applications. The developed in recent years pectin microparticle systems have several advantages over classical pectin gel formulations. These advantages include higher drug loading efficiency, reduced burst drug release, and the ability to better control the drug release and limit the polymer swelling. This review outlines the recent developments of pectin as a microcarrier in the production of drug delivery systems, which include the properties of the polysaccharide material essential for microparticle production, specific formulation methods with their key technological parameters, influencing the final microparticle product and potential applications of the proposed pectin microsized formulations.

Poly(N‐isopropylacrylamide)‐Based Polymers: Recent Overview for the Development of Temperature‐Responsive Drug Delivery and Biomedical Applications

AbstractTemperature is a widely incorporated stimulus in pharmaceutical applications because of its efficiency as a therapeutic medium; thus, substantial evidence on temperature‐responsive polymer applications is reported. Poly(N‐isopropylacrylamide) (PNIPAAm) is a well‐established, temperature‐responsive polymer that exhibits a low critical solution temperature (LCST) at ≈ 32°C, which is close to physiological temperature. Hence, they are widely used in various pharmaceutical applications, such as drug delivery with nanocarriers and thermogels. Varying the LCST for different applications can be achieved by copolymerization with other hydrophobic or hydrophilic molecules, making it a favorable smart polymer. PNIPAAm is reported to enhance drug delivery by incorporation with nanocarriers and to facilitate prolonged drug delivery, thereby avoiding the burst release of drugs in temperature‐responsive hydrogels. The application of PNIPAAm is not limited to drug delivery, and it is also applied in biomedical applications such as chromatography systems and cell culture applications, where its incorporation in cell culture media enhances cell production. The unique and versatile properties of PNIPAAm render it a promising smart polymer for various functional applications. Hence, this review focuses on the diverse applications of PNIPAAm.

Efficacy of co-loading Ag nanoparticles and metronidazole in PEG–gelatin-based sponges for the treatment of chronic wounds

Polymer-based sponges loaded with antibacterial agents are potential wound dressings ideal for treating bacteria-infected wounds. Gelatin/poly (ethylene glycol) (PEG) sponge-based wound dressings loaded with metronidazole and Ag nanoparticles with different degrees of cross-linking were prepared, and their capability to treat infected wounds in vitro was evaluated. The degree of cross-linking of the sponges varied, and the porosity of the sponges was in the range of 15.64–91.10%. The amount of gelatin used to prepare the sponges influenced the porosity of the sponges. The sponges displayed an initial burst drug release of metronidazole followed by a sustained release profile. The sponges exhibited considerable antibacterial activity against Gram-positive and Gram-negative bacteria. The % cell viability of the sponges was in the range of 71.17–86.10%, indicating distinguished biocompatibility. The in vitro experiment showed that the sponge loaded with metronidazole, SAM2%, displayed a significant reduction of 66.68% in the scratch area compared to the sponge loaded with a combination of silver nanoparticles and metronidazole with a closure rate of 46.61% at 96 h. The promising features of the sponges indicate that they are potential wound dressings for treating infected wounds.

Synthesis and evaluation of cross-linked gelatin nanoparticles for controlled release of an anti-diabetic drug: Gliclazide

The main problem with oral drug delivery using gelatin is rapid dissolution in aqueous mediums, which results in high-speed drug release. In the present study to overcome the challenge, we used glutaraldehyde to cross-link gelatin in order to control the burst release of drug. A drug delivery system based on gelatin nanoparticles (GNPs) for carrying Gliclazide was prepared by a two-step dissolution method. FTIR spectrum showed the presence of an aldimine functional group in GNPs, which confirms that gelatin structure is cross-linked by glutaraldehyde. XRD pattern showed that the crystallinity and crystal size of GNPs were 8% and 73 nm, respectively. SEM images showed the cross-linked structure of GNPs by glutaraldehyde, and DLS analysis exhibited an average particle size of about 88 nm. Ninhydrin assay showed the GNPs completely cross-linked for all ratios of gelatin to cross-linker (8%v/v, 16%v/v, and 25%v/v). After 8 h, the highest and lowest swelling percentages were related to cross-linked samples with 8%v/v and 25%v/v glutaraldehyde (in PBS buffer, pH=7.4, and 37 °C), respectively. The nanoparticle yield and drug loading were optimized via cross-linker concentration and GNPs: GLI ratio. The drug-release behavior from GNPs was controlled by the degree of swelling. The results showed that cross-linked GNPs via 8 %v/v and 25%v/v glutaraldehyde had the highest and lowest GLI release, (70% and 34% after 480 min, respectively, in PBS buffer, pH=7.4, and 37 °C). GLI release from GNPs showed controlled behavior compared with commercial anti-diabetic drugs, including Diabezide 80 mg and Diamicron MR 30 mg. MTT assay results showed that 94.5% of cells in contact with GLI-loaded GNPs survived.

Influence of Electrospun Fibre Secondary Morphology on Antibiotic Release Kinetic and Its Impact on Antimicrobic Efficacy.

Vascular graft infections are a severe complication in vascular surgery, with a high morbidity and mortality. Prevention and treatment involve the use of antibiotic- or antiseptic-impregnated artificial vascular grafts, but currently, there are no commercially available infection-proof small-diameter vascular grafts (SDVGs). In this work we investigated the antimicrobic activity of two SDVGs prototypes loaded with tobramycin and produced via the electrospinning of drug-doped PLGA (polylactide-co-glycolide) solutions. Differences in rheological and conductivity properties of the polymer solutions resulted in non-identical fibre morphology that deeply influenced the hydration profile and consequently the in vitro cumulative drug release, which was investigated by using a spectrofluorimetric technique. Using DDSolver Excel add-in, modelling of the drug release kinetic was performed to evaluate the release mechanism involved: Prototype 1 showed a sustained and diffusive driven drug release, which allowed for the complete elution of tobramycin within 2 weeks, whereas Prototype 2 resulted in a more extended drug release controlled by both diffusion and matrix relaxation. Time-kill assays performed on S. aureus and E. coli highlighted the influence of burst drug release on the decay rate of bacterial populations, with Prototype 1 being more efficient on both microorganisms. Nevertheless, both prototypes showed good antimicrobic activity over the 5 days of in vitro testing.

QbD driven targeted pulmonary delivery of dexamethasone-loaded chitosan microspheres: Biodistribution and pharmacokinetic study

Inhaling drugs, on the other hand, is limited mainly by the natural mechanisms of the respiratory system, which push drug particles out of the lungs or make them inefficient once they are there. Because of this, many ways have been found to work around the problems with drug transport through the lungs. Researchers have made polymeric microparticles (MP) and nanoparticles as a possible way to get drugs into the lungs. They showed that the drug could be trapped in large amounts and retained in the lungs for a long time, with as little contact as possible with the bloodstream. MP were formulated in this study to get dexamethasone (DMC) into the pulmonary area. The Box-Behnken design optimized microspheres preparation to meet the pulmonary delivery prerequisites. Optimized formulation was figured out based on the desirability approach. The mass median aerodynamic diameter (MMAD) of the optimized formula (O-DMC-MP) was 8.46 ± 1.45 µm, and the fine particle fraction (FPF) was 77.69 ± 1.26%. This showed that it made suitable drug delivery system, which could make it possible for MP to settle deeply in the lung space after being breathed in. With the first burst of drug release, it was seen that drug release could last up to 16 h. Also, there was no clear sign that the optimized formulation was toxic to the alveoli basal epithelial cells in the lungs, as supported by cytotoxic studies in HUVEC, A549, and H1299 cell lines. Most importantly, loading DMC inside MP cuts the amount of drug into the bloodstream compared to plain DMC, as evident from biodistribution studies. Stability tests have shown that the product can stay the same over time at both the storage conditions. Using chitosan DMC-MP can be a better therapeutic formulation to treat acute respiratory distress syndrome (ARDS).

Development of liposome capped mesoporous silica nanoparticle for anticancer drug delivery

AbstractMesoporous silica nanoparticles (MSNs) have been used as an anticancer drug delivery system with high safety and entrapment capacity thanks to their large internal space for drug accommodation, durable structure, and good biocompatibility. However, the treatment efficiency of the bare MSNs is limited due to its drug leakage and burst release. In this study, a phospholipid bilayer was covered on the MSNs surface (MSN@Lip) as a liposomal cap that not only reduced drug leakage but also improved the stability of the colloidal system. The chemical structure of MSNs and MSN@Lip was characterized by Fourier transform infrared spectroscopy (FT‐IR) and energy‐dispersive X‐ray spectroscopy (EDX). The particle size and morphology were determined by dynamic light scattering (DLS). The results demonstrated that the MSN@Lip was successfully synthesized with the hydrodynamic diameter and zeta potential of 177.13±1.5 nm and ‐57.57±4.00 mV, respectively. The optimal condition was sonication for 30 minutes at 60°C, with the Lip‐MSNs ratio as 3:1 (w/w). The SEM images showed that MSN@Lip has a spherical shape with high monodispersity. Releasing profile of doxorubicin (DOX) indicated that the formation of liposomal cap on MSN successfully reduced DOX burst release. The MSN@Lip is a potential delivery material for clinical translation because of colloidal stability, good drug loading content, and sustainable drug release.

Electrospun cellulose acetate/polyvinylpyrrolidone fiber mats as potential cosmetic under-eye masks for caffeine delivery

Cosmetic products for skin aging including infraorbital dark circles are getting popular. Caffeine incorporation into beauty skin masks is beneficial for this concern but the topical delivery of caffeine via this formulation remains deficient. This study aims to investigate cellulose acetate (CA)/polyvinylpyrrolidone K-90 (PVP) electrospun fiber mats for delivering caffeine to the skin as an under-eye mask. Polymer blends (7:3, 1:1 and 3:7) were first determined before loading with 5, 10 and 12.5%w/w caffeine. The electrospun fiber mats were evaluated for physicochemical properties, ex vivo skin adhesion, in vitro drug release, skin permeation and skin irritation. The polymer ratio at 7:3 was determined to be suitable (fiber diameter: ∼500 nm) due to its high flexibility and low tendency to absorb moisture. The loading of caffeine reduced the fiber diameter but increased the mechanical strength and flexibility saved for the highest drug loading, due to the drug-polymer interactions proven in FTIR and DSC analyses. A burst drug release for 5%w/w in the first 2 min was probably due to drug amorphicity while smaller fiber diameter and shorter diffusional pathlength contributed to a higher drug release of ∼85% at 24 h for 12.5%w/w. Both high drug loadings (10 and 12.5%w/w) showed similar skin permeation up to 6 h before the 12.5%w/w sample surpassed the 10%w/w sample. All mats showed no irritation in HET-CAM assay (irritation score = 0). In conclusion, the CA/PVP electrospun fiber mat at 10%w/w caffeine is a non-irritating cosmetic under-eye mask for delivering caffeine.

Formulation and in vitro evaluation of compression coated mebeverine HCl tablets for colon targeting

The aim of the study was to develop colon targeted compression coated Mebeverine HCl (MEB) tablets using pH dependent, swellable and rupturable polymers for effective treatment of irritable bowel syndrome (IBS). The MEB loaded core tablets were prepared by direct compression method using CCM and CP as super disintegrating agents at different concentrations and evaluated for pre compression and post compression parameters. The optimized core tablets were further used to fabricate compression coated tablets using different ratios of Eudragit L100, Eudragit S100 as pH- dependent polymers, Keltone and Ethocel as swellable and rupturable polymers by modified compression method. Drug compatibility with excipients was checked by FTIR studies and results indicate no interaction. The precompression and post compression studies were within acceptable limits. In vitro dissolution studies were done for compression coated tablets to find out the lag phase, burst drug release and retard drug release The findings of this study concludes that the lag time of compression coated tablet can be modulated by combining with EL 100, ES 100, Keltone and Ethocel in different weight ratio. These designed tablet system was found to be satisfactory in terms of release of the drug after the predetermined lag time, thus the system can be target to release in the colon proximity. The compression coating technique can be successfully applied for MEB for colon targeting to treat IBS.

Smart Microcapsules Designed for On-Demand Local Heating and Drug Release

Chemophotothermal therapy is promising for cancer treatment with its synergistic effect. Although various photothermal agents have been formulated as drug carriers, low payload, burst release, and severe dilution usually restrict their uses. To overcome the limitations, we design smart microcapsules as a pragmatic material for chemophotothermal therapy. With a microfluidic device, water-in-oil-in-water (W/O/W) double-emulsion templates are produced to have photothermal polydopamine nanoparticles and drugs in the water core and a mixture of photocurable monomers and phase-change material (PCM) in the oil shell. The droplets are significantly shrunken by the osmotic extraction of water from the core, which enables the size reduction for the ease of injection and enrichment of polydopamine nanoparticles and drugs for enhanced photothermal performance and high payload. The microcapsules, produced by photopolymerization of monomers, release drugs when PCM in continuous nanochannels of the polymer shell is molten while retaining drugs without leakage when frozen. As the concentrated polydopamine nanoparticles provide rapid and drastic heating by near-infrared irradiation, the drug release can be switched on and off in a programmed manner by manipulating the irradiation. The smart microcapsules secure high drug payload in a spacious core, negligible initial bursting, and dilution-free high photothermal performance, potentially serving as a pragmatic therapy platform.

Bioengineered nanogenerator with sustainable reactive oxygen species storm for self-reinforcing sono-chemodynamic oncotherapy

Oxidative stress-based antitumor modalities derived from reactive oxygen species (ROS) storms have attracted increasing attention. Nevertheless, low delivery efficiency, poor selectivity, hypoxia and overexpressed glutathione (GSH) have severely restricted the sustainable generation of the ROS storm in tumor cells. Herein, we design a bioengineered nanogenerator by coordination-driven co-assembly of sonosensitizer indocyanine green (ICG), Fenton-like agent copper ion (CuⅡ) and mitochondrial respiratory inhibitor metformin (MET), which is then camouflaged by a cancer cytomembrane to induce a sustainable intracellular ROS storm for on-demand self-reinforcing sono-chemodynamic oncotherapy. Such a nanogenerator with a core–shell structure, suitable diameter and outstanding stability can efficiently accumulate in tumor regions and then internalize into tumor cells through the camouflaging and homologous targeting strategy of the cancer cytomembrane. The nanogenerator shows an exceptional instability under the triple stimulations of acidic lysosomes, overexpressed GSH and ultrasound (US) radiation, thereby resulting in the rapid disassembly and burst drug release. Interestingly, the released MET significantly enhances the sonodynamic therapy (SDT) efficacy of the released ICG by inhibiting mitochondrial respiration and meanwhile the released CuⅡ obviously reduces ROS elimination by downregulating overexpressed GSH for self-amplifying and self-protecting the intracellular ROS storm. Moreover, such a nanogenerator almost completely achieves the tumor ablation in vivo in a single therapy cycle. Taken together, our bioengineered nanogenerator with a sustainable ROS storm can provide a promising strategy for ROS storm-based oncotherapy.