Development and evaluation of hollow mesoporous silica microspheres bearing on enhanced oral delivery of curcumin

The aim of this work is to develop curcumin-loaded hollow mesoporous silica microspheres (HMSMs@curcumin) to improve the poor oral bioavailability of curcumin. Hollow mesoporous silica microspheres (HMSMs) were synthesized in facile route using a hard template. HMSMs and HMSMs@curcumin were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption measurements, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). In addition, to demonstrate the potential application of the HMSMs@curcumin, cytotoxicity, in vitro release behavior and in vivo pharmacokinetics of curcumin loaded in these HMSMs were investigated by using of Caco-2 cells and Sprague-Dawley (SD) rats, respectively. These mono-dispersed HMSMs exhibited high drug loading ratio and encapsulation efficiency due to the mesoporous shell and hollow core. The excellent characteristics of HMSMs such as mono-dispersed morphology, smooth surface, uniform, ordered and size-narrowing mesopores resulted in a good in vitro release profile of curcumin from HMSMs@curcumin. Moreover, an impressive improvement in the oral absorption of curcumin and prolonged systemic circulation time were achieved in the in vivo animal studies. In addition, the good biocompatibility of developed HMSMs with Caco-2 cells was confirmed based on the in vitro cytotoxicity assay. In conclusion, this system demonstrated a great potential for efficient delivery of curcumin in vitro and in vivo, suggesting a good prospect for its application in clinic for therapeutic drug delivery in future.     

Freeze drying: exploring potential in development of orodispersible tablets of sumatriptan succinate

The present investigation is aimed at development and characterization of sumatriptan succinate orodispersible tablets (ODTs) prepared by freeze drying technology. The tablet excipients were screened and the composition was optimized based on parameters which involved general appearance, tablet size and shape, uniformity of weight, mechanical properties, surface pH, moisture analysis, drug content, wetting time, in vitro and in vivo disintegration time. Furthermore, fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron micrograph of cross-section of the tablet and in vitro dissolution studies were performed. Studies revealed that formulation containing gelatin–mannitol (3.75% w/v and 3.5% w/v, respectively) with camphor as a volatile pore forming agent exhibited superior properties with disintegration time of less than 10?s. Furthermore, in vitro release studies revealed 90% release of drug from developed dosage form within 10?min, thus suggesting rapid drug dissolution followed by faster onset of action, which forms a strong rationale for development of ODTs of sumatriptan succinate. The developed technology is simple, which involves few steps and can be easily scaled up. Thus, it holds enormous potential for commercial exploitation.     

Buccoadhesive films for once-a-day administration of rivastigmine: systematic formulation development and pharmacokinetic evaluation

Context: Rivastigmine, an anti-Alzheimer’s drug, suffers from major predicaments like low oral bioavailability, severe GI adverse effects related to rapid fluctuations in drug plasma levels, and high frequency of dosing.

Objective: The present investigation aims at developing buccoadhesive films capable of delivering the drug in vivo in a sustained manner. Augmentation of drug bioavailability by the avoidance of first-pass effect through the buccal route and reduction in GI side effects would be other key advantages of this system.

Methods: Buccoadhesive films of rivastigmine were systematically designed and evaluated for in vitro drug release, ex vivo buccal permeation and ex vivo buccoadhesive strength. Optimal composition of the polymer blends was rationally chosen using a central composite design and overlay plot. In vivo pharmacokinetic studies were carried out in rabbits, and attempts were made to establish in vitro/ in vivo correlations (IVIVC).

Results: Besides possessing the requisite drug release regulation, the optimized formulation exhibited excellent buccoadhesion, and buccal permeation. Pharmacokinetic studies indicated extension of plasma drug levels and level A of IVIVC was successfully established.

Discussion: Excellent buccal bioadhesion and transmucosal permeation, coupled with drug release control, ratify the potential of the optimized formulation to deliver the drug in a controlled and site-specific manner. Successful establishment of IVIVC substantiated the judicious choice of in vitro dissolution media for simulating the in vivo conditions.

Conclusion: Besides unraveling the polymer synergism, the study helped in developing an optimal once-a-day buccoadhesive drug delivery system exhibiting excellent trans-buccal permeation and buccoadhesive characteristics with improved bioavailability potential.     

Local drug delivery system for the treatment of osteomyelitis: In vitro evaluation

Local antimicrobial delivery is a potential area of research conceptualized to provide alternative and better methods of treatment for cases, as osteomyelitis where avascular zones prevent the delivery of drugs from conventional routes of administration. Drug-loaded polymers and calcium phosphates as hydroxyapatites have been tried earlier. Bioactive glasses are bone-filling materials used for space management in orthopedic and dental surgery. A new bioactive glass (SSS2) was synthesized and fabricated into porous scaffold with a view to provide prolonged local delivery of gatifloxacin and fluconazole as suitable for the treatment of osteomyelitis. The new SSS2 was characterized by Fourier transform infrared (FTIR) and X-ray diffraction (XRD) analyses. In addition, the bioactivity of the SSS2 glass and resulting scaffold was examined by in vitro acellular method and ascertained by FTIR and XRD. The pore size distribution was analysed by mercury intrusion porosimetry and the release of drugs from scaffolds were studied in vitro. The glass and the resulting scaffolds were bioactive indicating that they can bond with bone in vivo. The scaffolds were porous with pores predominantly in the range of 10–60 µm, released the drugs effectively for 6 weeks and deemed suitable for local delivery of drugs to treat osteomyelitis.     

Poly(lactide-co-glycolide) encapsulated hydroxyapatite microspheres for sustained release of doxycycline

The purpose of this study was to prepare a poly(lactide-co-glycolide) (PLGA) encapsulated hydroxyapatite microspheres (HAP-MSs) as injectable depot for sustained delivery of Doxycycline (Doxy). Doxy loaded HAP-MSs (Doxy-HAP-MSs) were encapsulated with PLGA by solid-in-oil-in-water (S/O/W) emulsion-solvent evaporation technique, the effects of the PLGA used (various intrinsic viscosity and LA/GA ratio) and ratio of PLGA/HAP-MSs on the formation of Doxy-HAP-MSs and in vitro release of Doxy were studied. The results showed that sustained drug release without obvious burst was obtained by using PLGA encapsulated HAP-MSs as the carrier, also the drug release rate could be tailored by changing the ratio of PLGA/HAP-MSs, or PLGA of various intrinsic viscosities or LA/GA ratio. Lower ratio of PLGA/HAP-MSs corresponded faster Doxy release, e.g. for the microspheres of PLGA/HAP-MSs ratio of 8 and 0.25, the in vitro Doxy release percents at the end of 7days were about 23% and 76%, respectively. Higher hydrophilicity (higher ratio of GA to LA) and lower molecular weight of PLGA corresponded to higher Doxy release rates. For in vivo release study, PLGA encapsulated HAP-MSs were subcutaneously injected to the back of mice, and the results showed good correlation between the in vivo and in vitro drug release. Meanwhile, the plasma Doxy levels after subcutaneous administration of PLGA encapsulated Doxy-HAP-MSs were relatively lower and steady compared to that of the un-encapsulated microspheres. In conclusion, PLGA encapsulated HAP-MSs may be a potential vehicle for the sustained delivery of Doxy.     

Potentials of proniosomes for improving the oral bioavailability of poorly water-soluble drugs

Objective: The objectives of this study were, first, to develop a free-flowing and stable proniosome formulation for poorly water-soluble drugs such as vinpocetine; and second, to estimate its bioavailability as oral drug delivery system.

Methods: The proniosomes consisting of span60, cholesterol, sorbitol and vinpocetine were prepared by a novel approach. After the proniosomes were contacted with water, the suspension of vinpocetine-loaded niosomes formed automatically. The proniosomes and reconstituted niosomes were evaluated for their physicochemical characteristics, in vitro drug dissolution and release, integrity and stability at different GI tract pH conditions, in situ single-pass intestinal perfusion and in vivo bioavailability.

Results: The proniosome powder exhibited excellent flowability. The reconstituted niosomes with high drug entrapment efficiency (89.67?±?3.28%) showed spherical morphology with smooth surface under transmission electron microscope (TEM). X-ray diffraction (XRD) indicated that the drug was in an amorphous or molecular state in proniosome powder. In vitro dissolution and release study, proniosomes did enhance the dissolution and release rate compared to vinpocetine suspension in phosphate buffer solution (pH 7.2). Proniosome-derived niosomes could keep their integrity and stability at different GI tract pH conditions. The in situ single-pass intestinal perfusion indicated that encapsulation of vinpocetine into niosomes could largely improved the absorption of vinpocetine. The AUC(0?∞) of F2 and F3 was about 4.0- and 4.9-fold higher than that of the vinpocetine suspension, respectively. The results demonstrated the proniosomes indeed remarkably enhanced the oral bioavailability of vinpocetine.

Conclusion: This study suggested the potential of proniosomes as stable precursors for the immediate preparation of niosome carrier systems.     

Tailoring morphological and interfacial properties of diatom silica microparticles for drug delivery applications

Diatomaceous earth (DE), naturally available silica, originated from fossilized diatoms has been explored for use in drug delivery applications as a potential substitute for synthetic silica materials. The aim of this study is to explore the influence of particle size, morphology and surface modifications of diatom silica microparticles on their drug release properties. Raw DE materials was purified and prepared to obtain high purity DE silica porous particles with different size and morphologies. Comparative scanning electron microscope and particle characterization confirmed their particle size including irregularly shaped silica particles (size 0.1–1 μm, classified as “fine”), mixed fractions (size 1–10 μm, classified as “mixture”) and pure, unbroken DE structures (size 10–15 μm, classified as “entire”). Surface modification of DE with silanes and phosphonic acids was performed using standard silanization and phosphonation process to obtain surface with hydrophilic and hydrophobic properties. Water insoluble (indomethacin) and water soluble (gentamicin) drugs were loaded in DE particles to study their drug release performances. In vitro drug release studies were performed over 1–4 weeks, to examine the impact of the particle size and hydrophilic/hydrophobic functional groups. The release studies showed a biphasic pattern, comprising an initial burst release for 6 h, followed by near-zero order sustained release. This study demonstrates the potential of silica DE particles as a natural carrier for water soluble and insoluble drugs with release controlled by their morphological and interfacial properties.     

Preparation of magnetic mesoporous silica nanoparticles as a multifunctional platform for potential drug delivery and hyperthermia

We report the preparation of magnetic mesoporous silica (MMS) nanoparticles with the potential multifunctionality of drug delivery and magnetic hyperthermia. Carbon-encapsulated magnetic colloidal nanoparticles (MCN@C) were used to coat mesoporous silica shells for the formation of the core-shell structured MMS nanoparticles (MCN@C/mSiO₂), and the rattle-type structured MMS nanoparticles (MCN/mSiO₂) were obtained after the removal of the carbon layers from MCN@C/mSiO₂ nanoparticles. The morphology, structure, magnetic hyperthermia ability, drug release behavior, in vitro cytotoxicity and cellular uptake of MMS nanoparticles were investigated. The results revealed that the MCN@C/mSiO₂ and MCN/mSiO₂ nanoparticles had spherical morphology and average particle sizes of 390 and 320 nm, respectively. The MCN@C/mSiO₂ nanoparticles exhibited higher magnetic hyperthermia ability compared to the MCN/mSiO₂ nanoparticles, but the MCN/mSiO₂ nanoparticles had higher drug loading capacity. Both MCN@C/mSiO₂ and MCN/mSiO₂ nanoparticles had similar drug release behavior with pH-controlled release and temperature-accelerated release. Furthermore, the MCN@C/mSiO₂ and MCN/mSiO₂ nanoparticles showed low cytotoxicity and could be internalized into HeLa cells. Therefore, the MCN@C/mSiO₂ and MCN/mSiO₂ nanoparticles would be promising for the combination of drug delivery and magnetic hyperthermia treatment in cancer therapy.     

Facile development,characterization, and evaluation of novel bicalutamide loaded pH-sensitive mesoporous silica nanoparticles for enhanced prostate cancer therapy

It is a challenge to deliver therapeutics exclusively to cancer cells, while sparing the normal cells. However, pH-sensitive delivery systems have proved to be highly efficient in fulfilling this task due to their ability to provide on-demand and selective release of drug at acidic tumor sites. As a proof of concept, here pH responsive drug delivery system based on mesoporous core shell nanoparticles (NPs) surrounded with poly acrylic acid (PAA) layers were prepared employing a facile synthesis strategy. Bicalutamide (BIC) was encased into surface functionalized MCM-41 nanoparticles via electrostatic interactions. The synthesized NPs were characterized by nitrogen adsorption and desorption isotherms, SEM-EDS, TEM, LXRD, and WXRD. In vitro release studies demonstrated that BIC-MSN-PAA NPs exhibited a higher release in the acidic media which varied inversely with the increase in pH. Further, the results of cell cytotoxicity assay were evident that BICMSNs exhibited more potent killing of both PC-3 and LNCaP cells than free BIC. PAA-MSNs also exhibited an enhanced cellular uptake and prolonged circulation time in vivo. The results are suggestive of the fact that PAA functionalized MSNs can serve as an effective pH-responsive template and hold a great potential ahead in controlled release and effective cancer treatment.     

Preparation of novel porous starch microsphere foam for loading and release of poorly water soluble drug

Background: Organic porous material is a promising carrier for enhancing the dissolution of poorly water soluble drug. The aim of the present study was to enhance dissolution and oral bioavailability of lovastatin (LV) by preparing a porous starch microsphere foam (PSM) using a novel method, meanwhile, looking into the mechanism of improving dissolution of LV.

Methods: PSM was prepared by the W/O emulsion – freeze thawing method. The porous structure of PSM was characterized by scanning electron microscopy (SEM) and nitrogen adsorption/desorption analysis. The adsorption role of nanopores on the drug dissolution and physical state of LV was systematically studied by instrumental analysis, and in vitro and in vivo drug dissolution studies. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate carrier cytotoxicity.

Results: The SEM images of PSM showed nanometer-sized pores. Physical state characterization indicated that porous structure effectively limited the degree of crystallinity of LV. The results of in vitro and in vivo tests testified that PSM accelerated the release of LV and enhanced its oral bioavailability in comparison with crude LV and commercial capsules. The loaded PSM powder indicated a good physical stability under storage for 12 months. MTT assay shows PSM has no toxicity for Caco-2 cell.

Conclusion: The preparation was a promising method to produce small and uniform PSM with markedly enhanced dissolution rate and oral bioavailability due to the spatial confinement effect of porous structure. The present work demonstrates the significant potential for the use of PSM as a novel delivery system for poorly water soluble drugs.     

Development of ocular drug delivery systems using molecularly imprinted soft contact lenses

Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug-loading capacity, and the release properties of molecularly imprinted hydrogels.     

Development of novel core-shell dual-mesoporous silica nanoparticles for the production of high bioavailable controlled-release fenofibrate tablets

Novel core-shell dual-mesoporous silica nanoparticles (DMSN) were successfully prepared as a carrier in order to improve the dissolution of fenofibrate and obtain an oral highly bioavailable controlled-release drug delivery system using the osmotic pump technology. Fenofibrate was loaded into DMSN by an adsorption method. The solid state properties of fenofibrate in DMSN, before and after drug loading, were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption analysis (BET), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). In vitro release tests showed that DMSN increased the dissolution rate of fenofibrate and produced zero-order release in push–pull osmotic pump tablets (OPT). The relative bioavailability of OPT was 186.9% in comparison with the commercial reference product. In summary, osmotic pump technology in combination with solid dispersion technology involving nanometer materials is a promising way for achieving the oral delivery of poorly water-soluble drugs.     

Phytantriol based liquid crystal provide sustained release of anticancer drug as a novel embolic agent

Phytantriol has received increasing amount of attention in drug delivery system, however, the ability of the phytantriol based liquid crystal as a novel embolic agent to provide a sustained release delivery system is yet to be comprehensively demonstrated. The purpose of this study was to prepare a phytantriol-based cubic phase precursor solution loaded with anticancer drug hydroxycamptothecine (HCPT) and evaluate its embolization properties, in vitro drug release and cytotoxicity. Phase behavior of the phytantriol–solvent–water system was investigated by visual inspection and polarized light microscopy, and no phase transition was observed in the presence of HCPT within the studied dose range. Water uptake by the phytantriol matrices was determined gravimetrically, suggesting that the swelling complied with the second order kinetics. In vitro evaluation of embolic efficacy indicated that the isotropic solution displayed a satisfactory embolization effect. In vitro drug release results showed a sustained-release up to 30 days and the release behavior was affected by the initial composition and drug loading. Moreover, the in vitro cytotoxicity and anticancer activity were evaluated by MTT assay. No appreciable mortality was observed for NIH 3T3 cells after 48?h exposure to blank formulations, and the anticancer activity of HCPT-loaded formulations to HepG2 and SMMC7721 cells was strongly dependent on the drug loading and treatment time. Taken together, these results indicate that phytantriol-based cubic phase embolic gelling solution is a promising potential carrier for HCPT delivery to achieve a sustained drug release by vascular embolization, and this technology may be potential for clinical applications.     

In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization

Context and objective: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery.

Materials and methods: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings.

Results and discussion: There was a big deviation between the T_g of the polymeric caplet from the T_g's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012–0.332?mg/mL and 0.009–0.256?mg/mL for AZT and PSS over 1–28 d.

Conclusion: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.     

Prediction of in vivo drug performance using in vitro dissolution coupled with STELLA: a study with selected drug products

Prediction of the in vivo performance of the drug product from the in vitro studies is the major challenging job for the pharmaceutical industries. From the current regulatory perspective, biorelevant dissolution media should now be considered as quality control media in order to avoid the risk associated. Physiological based pharmacokinetic models (PBPK) coupled with biorelevant dissolution medium is widely used in simulation and prediction of the plasma drug concentration and in vivo drug performance. The present investigation deals with the evaluation of biorelevant dissolution media as well as in vivo drug performance by PBPK modelling using STELLA® simulation software. The PBPK model was developed using STELLA® using dissolution kinetics, solubility, standard gastrointestinal parameters and post-absorptive disposition parameters. The drug product selected for the present study includes Linezolid film-coated immediate-release tablets (Zyvox), Tacrolimus prolonged-release capsules (Advagraf), Valganciclovir tablets (Valcyte) and Mesalamine controlled-release capsules (Pentasa) each belonging to different biopharmaceutics classification system (BCS). The simulated plasma drug concentration was analyzed and pharmacokinetic parameters were calculated and compared with the reported values. The result from the present investigation indicates that STELLA® when coupled with biorelevant dissolution media can predict the in vivo performance of the drug product with prediction error less than 20% irrespective of the dosage form (immediate release versus modified release) and BCS Classification. Thus, STELLA® can be used for in vivo drug prediction which will be helpful in generic drug development.     

Assessment of critical material attributes of polyethylene oxide for formulation of prolonged-release tablets

Abstract

Physicochemical evaluation of polyethylene oxide (PEO) polymers with various molecular weights was performed at molecular (polymeric dispersion) and bulk level (powders, polymeric films, and tablets) with the aim of specifying polymer critical material attributes with the main contribution to drug release from prolonged-release tablets (PRTs). For this purpose, grades of PEO with low, medium, and high viscosity were used for formulating PRTs with a good soluble drug substance (dose solubility volume 15?ml). The results revealed a good correlation (r²=0.88) between in?vivo data (pharmacokinetic parameters: C_max and AUC) and the elastic property of PEO films determined with the nanoindentation method, demonstrating that film level can also be used for the in?vivo prediction of drug dissolution. The study confirmed that polymer molecular weight and its viscosity are the most important critical material attributes affecting drug dissolution (in?vitro) and in?vivo bioavailability (e.g. C_max and AUC). Our research revealed that the nanoindentation technique can distinguish well between various types of polymers, classifying PEO as the most ductile and polyvinyl alcohol as the most brittle. Finally, our study provides an approach for the determination of exact physical attributes of PEO as a critical material attribute from clinically relevant data, and it therefore fulfills the basic principles of product development by Quality by Design.     

Flocculated amorphous itraconazole nanoparticles for enhanced in vitro supersaturation and in vivo bioavailability

Rapid flocculation of nanoparticle dispersions of a poorly water soluble drug, itraconazole (Itz), was utilized to produce amorphous powders with desirable dissolution properties for high bioavailability in rats. Antisolvent precipitation (AP) was utilized to form Itz nanodispersions with high drug loadings stabilized with hydroxypropylmethylcellulose (HPMC) or the pH-sensitive Eudragit^® L100-55 (EL10055). The HPMC dispersions were flocculated by desolvating the polymer through the addition of a divalent salt, and the enteric EL10055 by reducing the pH. The formation of open flocs by diffusion limited aggregation facilitated redispersion of the flocs at pH 6.8. Upon redispersion of the flocculated nanoparticles at pH 6.8, the particle size was modestly larger than the original size, on the order of 1 μm. High in vitro supersaturation (AUC) of the flocculated nanoparticle dispersions was observed in micellar media at pH 6.8, after 2 hours initial exposure at pH 1.2 to simulate the stomach, relative to the AUC for a commercially available Itz formulation, Sporanox. Greater in vivo bioavailability in rats was correlated directly to the higher in vitro AUC at pH 6.8 with micelles during the pH shift experiment for the flocculated nanoparticle dispersions relative to Sporanox. The ability to generate and sustain high supersaturation in micellar media at pH 6.8, as shown with the in vitro pH shift dissolution test, is beneficial for increasing bioavailability of Itz by oral delivery.     

Galactose decorated PLGA nanoparticles for hepatic delivery of acyclovir

The present study explores prospective of surface tailored nanoparticles for targeted delivery of acyclovir along with the interception of minimal side effects. Acyclovir loaded plain and galactosylated poly lectic co glycolic acid (PLGA) nanoparticles were efficiently prepared and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), size, polydispersity index, zeta potential, and entrapment efficiency. The formulations were evaluated for in vitro drug release and hemolysis. Further, biodistribution study and fluorescent microscopic studies were carried out to determine the targeting potential of formulations. SEM revealed smooth morphology and spherical shape of the nanoparticles. In vitro, the galactosylated nanoparticles were found to be least hemolytic and exhibited a sustained release pattern. In vivo studies exhibited an augmented bioavailability, increased residence time and enhanced delivery of acyclovir to the liver upon galactosylation. It may therefore be concluded that galactose conjugated PLGA nanoparticles can be used suitably as vehicles for delivery of bioactives specifically to the hepatic tissues and may be thus exploited in the effective management of various liver disorders.     

Ionic liquid-assisted synthesis of silica particles and their application in drug release

Hollow and porous silica particles have been successfully prepared by a simple acid gelation route using the sodium silicate as the reactant in ionic liquid solution, 1-butyl-3-methylimidazolium tetrafluoroborate. The drug release behavior of the as-prepared porous silica particles is studied to reveal their potential use in drug delivery system. The current work for the synthesis of silica particles with the sodium silicate as the reactant in an ionic liquid might open new directions and opportunities to explore the application of ionic liquid in materials fields combining with the biomedical area.     

The investigation of MCM-48-type and MCM-41-type mesoporous silica as oral solid dispersion carriers for water insoluble cilostazol

Objective: To explore the suitable application of MCM-41 (Mobil Composition of Matter number forty-one)-type and MCM-48-type mesoporous silica in the oral water insoluble drug delivery system.

Methods: Cilostazol (CLT) as a model drug was loaded into synthesized MCM-48 (Mobil Composition of Matter number forty-eight) and commercial MCM-41 by three common methods. The obtained MCM-41, MCM-48 and CLT-loaded samples were characterized by means of nitrogen adsorption, thermogravimetric analysis, ultraviolet-visible spectrophotometry, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry and powder X-ray diffractometer.

Results: It was found that solvent evaporation method was preferred according to the drug loading efficiency and the maximum percent cumulative drug dissolution. MCM-48 with 3D cubic pore structure and MCM-41 with 2D long tubular structure are nearly spherical particles in 300–500?nm. Nevertheless, the silica carriers with similar large specific surface areas and concentrating pore size distributions (978.66?m²/g, 3.8?nm for MCM-41 and 1108.04?m²/g, 3.6?nm for MCM-48) exhibited different adsorption behaviors for CLT. The maximum percent cumulative drug release of the two CLT/silica solid dispersion (CLT-MCM-48 and CLT-MCM-41) was 63.41% and 85.78% within 60?min, respectively; while in the subsequent 12?h release experiment, almost 100% cumulative drug release were both obtained. In the pharmacokinetics aspect, the maximum plasma concentrations of CLT-MCM-48 reached 3.63?mg/L by 0.92?h. The AUC_0–∞ values of the CLT-MCM-41 and CLT-MCM-48 were 1.14-fold and 1.73-fold, respectively, compared with the commercial preparation.

Conclusion: Our findings suggest that MCM-41-type and MCM-48-type mesoporous silica have great promise as solid dispersion carriers for sustained and immediate release separately.