Mean Release Time Research Articles

Polycaprolactone microparticles for the subcutaneous administration of cannabidiol: in vitro and in vivo release.

Cannabidiol (CBD) has become a highly attractive entity in therapeutics. However, its low aqueous solubility, instability and handling problems limit the development of effective CBD formulations. Subcutaneously administered CBD-loaded polycaprolactone microparticles (MP) represent an interesting strategy to overcome these challenges. This work focuses on evaluating the pharmacokinetics of CBD formulated in polymer microparticles for subcutaneous administration and characterising its release. The mean release time (MRLT) parameter is used to compare the release of CBD from two microparticle formulations in vitro and in a mouse model. After the administration of CBD in solution, a bicompartmental distribution is observed due to the extensive diffusion to the brain, being the brain/blood AUC ratio 1.29. The blood and brain mean residence time (MRT) are 0.507 ± 0.04 and 0.257 ± 0.0004days, respectively. MP prepared with two drug/polymer ratios (15/150-MP and 30/150-MP) are designed, showing similar in vitro dissolution profiles (similarity factor (f2) is 63.21), without statistically significant differences between MRLTin vitro values (4.68 ± 0.63 and 4.32 ± 0.05days). However, considerable differences in blood and brain profiles between both formulations are detected. The blood and brain MRT values of 15/150-MP are 6.44 ± 0.3days and 6.15 ± 0.25days, respectively, whereas significantly lower values 3.91 ± 0.29days and 2.24 ± 0.64days are obtained with 30/150-MP. The extended release of CBD during 10days after a single subcutaneous administration is achieved.

Microparticulation of Levofloxacin HCl by Crystallo-co-agglomeration Technique

Particle engineering techniques have gained a unique place in the present pharma industry to improve physicochemical properties of the drugs. The aim of this research work was to formulate and evaluate directly compressible agglomerates of Levofloxacin HCl with a view to improve their micromeritic properties and thereby to reduce the cost of production. Fluoroquinolone anti-infective, is used to treat bacterial conjunctivitis, sinusitis, chronic bronchitis, community- acquired pneumonia and pneumonia caused by penicillin resistant strains of Streptococcus pneumonia. Some of the fluoroquinolone high dose’s exhibit poor compressibility and flow properties, hence may not be suitable candidate for direct compression process, but by applying the crystallo-co-agglomeration (CCA) technique, the attempt may be made to change the properties of these molecules to make them suitable candidates for direct compression. This investigation was aimed to utilize CCA process to develop spherical agglomerates of levofloxacin HCl in selected polymers in different ratio. The developed spherical agglomerates of levofloxacin HCl may exhibit improved micrometric and dissolution properties hence may be suitable for direct compression process. Results indicated that micromeritic, mechanical and compressional properties of the agglomerates were greatly influenced by nature and type of polymer incorporated. The mean release time, mean dissolution time, dissolution efficiency, Q30 and Q90 of the tablets prepared from agglomerates showed remarkable increase in CCA compared to tablets prepared by wet granulation. Observations also revealed that by varying the type and concentration of polymer, desired release rate can be obtained.

Risedronate-loaded aerogel scaffolds for bone regeneration

Sugarcane bagasse-derived nanofibrillated cellulose (NFC), a type of cellulose with a fibrous structure, is potentially used in the pharmaceutical field. Regeneration of this cellulose using a green process offers a more accessible and less ordered cellulose II structure (amorphous cellulose; AmC). Furthermore, the preparation of cross-linked cellulose (NFC/AmC) provides a dual advantage by building a structural block that could exhibit distinct mechanical properties. 3D aerogel scaffolds loaded with risedronate were prepared in our study using NFC or cross-linked cellulose (NFC/AmC), then combined with different concentrations of chitosan. Results proved that the aerogel scaffolds composed of NFC and chitosan had significantly improved the mechanical properties and retarded drug release compared to all other fabricated aerogel scaffolds. The aerogel scaffolds containing the highest concentration of chitosan (SC-T3) attained the highest compressive strength and mean release time values (415 ± 41.80 kPa and 2.61 ± 0.23 h, respectively). Scanning electron microscope images proved the uniform highly porous microstructure of SC-T3 with interconnectedness. All the tested medicated as well as unmedicated aerogel scaffolds had the ability to regenerate bone as assessed using the MG-63 cell line, with the former attaining a higher effect than the latter. However, SC-T3 aerogel scaffolds possessed a lower regenerative effect than those composed of NFC only. This study highlights the promising approach of the use of biopolymers derived from agro-wastes for tissue engineering.

PREDICTIVE FACTORS OF SPONTANEOUS RELEASE OF VITREOMACULAR TRACTION: A Systematic Review and Meta-Analysis.

To review predictive factors of spontaneous vitreomacular traction (VMT) release. A systematic literature search was performed on Ovid MEDLINE, Embase, and Cochrane Library. Studies comparing spontaneously released VMT to persistent VMT were included. A meta-analysis was performed using a random effects model, and weighted mean difference, risk ratio (RR), and 95% confidence intervals (95% CI) were reported as appropriate. Of a search of 258 studies, 12 studies were included, from which 272 of 934 eyes (29%) underwent spontaneous release. Mean age was 70.0 years, 37.2% of patients were men, and mean follow-up was 22.0 months. Significant predictive factors for spontaneous release were smaller VMT diameter (n = 177; weighted mean difference = -212.48 µm, 95% CI = [-417.36, -7.60], P = 0.04), epiretinal membrane absence (n = 162; RR = 2.17, 95% CI = [1.18, 3.97], P = 0.01), and right eye involvement (n = 76; RR = 2.10, 95% CI = [1.14, 3.88], P = 0.02). Nonsignificant factors were age, initial best-corrected visual acuity, sex, ocular comorbidity, fellow-eye posterior vitreous detachment, previous intravitreal injection, and VMT classification with focal defined as ≤400 µm. Mean release time was 15.3 months (n = 212). Mean best-corrected visual acuity improved from 0.34 ± 0.21 (Snellen 20/44) to 0.20 ± 0.58 logMAR (Snellen 20/32) postrelease (n = 121). Smaller VMT diameter, epiretinal membrane absence, and right eye involvement may support spontaneous VMT release. If patients have tolerable symptoms, clinicians may consider observation in patients with these predictive factors.

Development of a potential anti-cancer pulmonary nanosystem consisted of chitosan-doped LeciPlex loaded with resveratrol using a machine learning method

A novel self-assembled lecithin-based cationic nanocarrier (LeciPlex) doped with chitosan was prepared to improve Resveratrol solubility and anticancer efficacy. Using on a machine learning method based on regression analysis, LP5 (composed of lecithin, Peceol® and chitosan) was selected as the optimized one. This formula was spherical-shaped with a particle size of 59 nm, an encapsulation efficiency of 89% and a mean release time of 2.75 h together with a good mucoadhesive potential. Cascade impactor studies revealed the possible deep lung deposition of LP5 after nebulization. The safety of Resveratrol suspension and LP5 were checked on WISH cell line. Compared with Doxorubicin, both Resveratrol suspension and LP5 showed potent anticancer effects against the A549 cell line with IC50 values of 2.312, 2.200 and 1.708 μg/ml, respectively. These results indicated that the selected formula (LP5) significantly enhanced the crude drug anticancer effect by 63.2 fold and showed a higher anticancer selectivity index (>5.51). Furthermore, after 24 h, A549 up-took the LP5 more than the drug suspension by 40,000 fold. In addition, LP5 markedly induced the cellular apoptosis in A549 treated cells with a percentage of 73.1 compared to untreated cells. In conclusion, the results confirmed the enhanced lung anticancer effect, lower toxicity, and higher selectivity of the selected Resveratrol-loaded LeciPlex compared to the drug suspension. This study presents a potential nano-vesicular system for nebulization to combat lung cancer.

Pulmonary Delivery of Docetaxel and Celecoxib by PLGA Porous Microparticles for Their Synergistic Effects Against Lung Cancer.

Using a combination of chemotherapeutic agents with novel drug delivery platforms to enhance the anticancer efficacy of the drug and minimizing the side effects, is imperative to lung cancer treatments. The aim of the present study was to develop, characterize, and optimize porous poly (D, L-lactic-co-glycolic acid) (PLGA) microparticles for simultaneous delivery of docetaxel (DTX) and celecoxib (CXB) through the pulmonary route for lung cancer. Drug-loaded porous microparticles were prepared by an emulsion solvent evaporation method. The impact of various processing and formulation variables including PLGA amount, dichloromethane volume, homogenization speed, polyvinyl alcohol volume, and concentration, was assessed based on entrapment efficiency, mean release time, particle size, mass median aerodynamic diameter, fine particle fraction, and geometric standard deviation using a twolevel factorial design. An optimized formulation was prepared and evaluated in terms of size and morphology using a scanning electron microscope. FTIR, DSC, and XRD analyses confirmed drug entrapment and revealed no drug-polymer chemical interaction. Cytotoxicity of DTX along with CXB against A549 cells was significantly enhanced compared to DTX and CXB alone and the combination of DTX and CXB showed the greatest synergistic effect at a 1/500 ratio. In conclusion, the results of the present study suggest that encapsulation of DTX and CXB in porous PLGA microspheres with desirable features is feasible and their pulmonary co-administration would be a promising strategy for the effective and less toxic treatment of various lung cancers.

Nanofibrillated cellulose/glucosamine 3D aerogel implants loaded with rosuvastatin and bioactive ceramic for dental socket preservation

Recycling of agro-wastes presents a great economic and ecologic value. In this study, TEMPO-oxidized nanofibrillated cellulose (TONFC) originating from sugarcane bagasse pulp was exploited in regenerative medicine. TONFC in combination with glucosamine HCl (G) were used to prepare a 3D aerogel implant loaded with rosuvastatin as an integrative approach for extraction-socket healing. Comparing the prepared devices, aerogel composed of TONFC: G (4:1 wt ratio) had the best mechanical properties and integrity. Strontium borate-based bioactive ceramic particles were prepared and characterized for crystal structure, shape, porosity, and zeta potential. The particles had a crystalline diffraction pattern relative to Sr3B2O6, and they were rod in shape with nanopores with a zeta potential value of −16 mV. The prepared bioactive ceramic (BC) was then added in different concentrations (3 or 6% w/w) to the selected aerogel implant. The BC had a concentration-dependent effect on the aerogel properties as it ameliorated its mechanical performance (compressive strength = 90 and 150 kPa for 3 and 6%, respectively) and retarded drug release (mean release time = 2.34 and 3.4 h for 3 and 6%, respectively) (p < 0.05). The microphotograph of the selected aerogel implant loaded with BC showed a rough surface with an interconnective porous structure. During cell biology testing, the selected implant loaded with the lower BC concentration had the highest ability to increase MG-63 cells proliferation. In conclusion, TONFC is a promising material to formulate rosuvastatin-loaded aerogel implant with the aid of glucosamine and bioactive ceramic for dental socket preservation.

CO2-assisted production of polyethylene glycol / lauric acid microparticles for extended release of Citrus aurantifolia essential oil

Applications of essential oils as chemotherapeutics are limited because these aromatic oils are generally volatile, insoluble in aqueous media and easily degraded to non-active constituents when subjected to thermal-oxidative processes. The particles from gas-saturated solution (PGSS) technology allows for non-destructive processing of volatile oils into micronized formulations under high pressure and moderate temperature using supercritical carbon dioxide (scCO2). In this study, essential oil from lime (Citrus aurantifolia) with proven antidiabetic activity was processed with polyethylene glycol (PEG) and lauric acid (LA) using scCO2 in a high pressure reactor for 2 h at 120 bar and 45 °C. The polymer-oil mixtures were co-precipitated and micronized through a 500 μm nozzle. PGSS processing of C. aurantifolia oil with PEG and LA yielded roughly spherical microparticles with sizes ∼ 2 μm. Inclusion of the LA and encapsulation of the limonene-rich oil into the PEG particles were confirmed using FTIR and GC/MS respectively. Melting point and heat of fusion of the PEG/LA microparticles were lower when compared with particles produced with PEG only, resulting in higher oil loading capacity and yield. The scCO2-assisted polymeric encapsulation of the volatile oil reduced rapid vaporization and incorporation of LA with the PEG-oil formulation extended the mean release time in simulated physiological solutions. Free radical scavenging and alpha-amylase inhibitory activities of the lime oil were also preserved following encapsulation in the PEG/LA microparticles. In summary, production of PEG/LA microparticles with high yield and loading capacity of bioactive lime essential oil was achieved using the scCO2 encapsulation technology.

Pneumatic Vitreolysis for the Treatment of Vitreomacular Traction Syndrome

Objectives:To evaluate the posterior vitreous release rates after a single injection of expansile gas in patients with vitreomacular traction (VMT) syndrome with or without associated full-thickness macular hole (FTMH).Materials and Methods:Thirteen eyes of 12 consecutive patients with VMT (11 eyes) or VMT+FTMH (2 eyes) were reviewed retrospectively. Intravitreal injection of 0.3 mL of pure sulfur hexafluoride (SF6) (9 eyes) or perfluoropropane (C3F8) (4 eyes) was performed. Bobbing the head forward and backward similar to ‘drinking bird’ head movements was instructed until VMT release. Full ophthalmic examination and optical coherence tomography was performed at each visit.Results:VMT was released in all patients (100%) and mean release time was 5.2 days (1-19 days). Macular hole closure was not achieved in either of the two eyes with FTMH. Mean central subfield thickness decreased significantly from 361 μm to 263 μm (p=0.007). The mean pretreatment visual acuity was 0.44 LogMAR, which significantly improved to 0.25 LogMAR at the last visit (p=0.003). One of 13 eyes had retinal tear after the procedure which was successfully treated with laser retinopexy. Gas migration to the anterior chamber occurred in one patient. No other complications were observed.Conclusion:Pneumatic vitreolysis with C3F8 and SF6 gases is a relatively safe, low-cost, and minimally invasive treatment modality for VMT. However, FTMH closure could not be achieved with pneumatic vitreolysis.

FORMULATION, OPTIMIZATION, AND EVALUATION OF IN-SITU GEL OF MOXIFLOXACIN HYDROCHLORIDE FOR OPHTHALMIC DRUG DELIVERY

Objective: The present study emphasizes the synthesis, optimization, and evaluation of ocular in-situ gel for ophthalmic drug delivery against conjunctivitis.&#x0D; Methods: Pre-formulation studies on the drug and polymers were carried out, which included the study of various physicochemical properties of the drug and drug-polymer compatibility studies. The 12 different formulations were further pre-optimised by Taguchi method for determining the number of influential factors. Furthermore, the formulation optimization was done by using ‘Box–Behnken’ design (BBD) (Design expert 10 software) for assessing the effect of formulation variables on product characteristics viz. viscosity, gelation temperature (GT), and mean release time (MRT). About 13 suggested runs of the experiment were carried out and formulations were optimised. Finally, three batches of the optimised formulation were prepared and evaluated for in vitro drug release, isotonicity of formulation, anti-microbial potential, ocular irritancy, and accelerated stability testing.&#x0D; Results: Pre-formulation study confirmed the purity, solubility, and compatibility of drug measured by λmax, partition coefficient, stability study, and Fourier-transform infrared spectroscopy (FTIR) analysis. Taguchi screening method suggested about 12 different formulations and 3 most prominent influential factors including viscosity, GT, and drug release. 13 different formulations designed based on ‘BBD’ method were further optimised by considering the most influential factors suggested by Taguchi screening. The in vitro evaluation of the optimised formulation gave satisfactory results in terms of drug release, and anti-microbial activity. It was found to be isotonic with no ocular irritancy. Further, the preparation immediately transformed from sol to gel upon administration into cul-de-sac region of the eye due to multi-dimensional approaches utilised for in-situ gel formation namely temperature change Pluronic, ion sensitivity due to Gellan-gum, pH sensitivity because of Carbopol.&#x0D; Conclusion: The optimised in-situ gelling ocular drug formulation showed promising potency for ophthalmic drug delivery with no irritancy due to the multifactorial mechanism.

Targeted Nanostructured Lipid Carrier for Brain Delivery of Artemisinin: Design, Preparation, Characterization, Optimization and Cell Toxicity.

In the present study, a transferrin-conjugated nanostructured lipid carrier (TF-NLCs) for brain delivery of artemisinin (ART) was developed. ART-loaded NLCs (ART-NLCs) were prepared using solvent evaporation method and the impact of various formulation or process variables on the responses were assessed using a Taguchi design. Optimized ART-NLC was then coupled with transferrin as targeting ligand and its in vitro cytotoxicity was investigated against U-87MG brain cancer cell line. As a result, the following values are suggested by the software to prepare the optimized formulation: 20 mg Compritol®, 0.25% Tween 80, 5 mg oleic acid, 2.5 mL dichloromethane and 4 min sonication. Mean particle size (PS), zeta potential (ZP), polydispersity index (PDI), entrapment efficiency (EE), mean release time (MRT) of adopted formulation were confirmed to be 145 ± 12.5 nm, 24.3 ± 1.5 mV, 0.513 ± 0.021, 82.3 ± 7.3 % and 24.0 ± 1.1 h, respectively. Following conjugation of optimized ART-NLCs with TF, PS and MRT were increased, while ZP, and EE were decreased significantly. TF-ART-NLCs showed higher cytotoxic activity compared to non-targeted NLCs and free drug. These results indicated that the TF-ART-NLCs could potentially be exploited as a delivery system for anticancer and antimalarial drug ART in brain tumors and malaria.

Incorporation of rosuvastatin-loaded chitosan/chondroitin sulfate nanoparticles into a thermosensitive hydrogel for bone tissue engineering: preparation, characterization, and cellular behavior

Rosuvastatin (RSV) has been shown to have significant impact on the simulation of bone regeneration after local injection. The current study aimed to develop a localized controlled delivery system from RSV by incorporating RSV-loaded chitosan/chondroitin sulfate (CTS/CS) nanoparticles into thermosensitive Pluronic F127/hyaluronic acid (PF127/HA) hydrogel. RSV-loaded CTS/CS nanoparticles were prepared by ionic gelation, and the impact of various formulation variables was assessed using the Box–Behnken design. Consequently, optimized RSV-loaded nanoparticles were incorporated into the PF127/HA hydrogel. Rheological properties, degradation rates of hydrogels, and the release rate of RSV from hydrogel were examined. Mean particle size, zeta potential, entrapment efficiency, and mean release time of the optimized RSV-loaded nanoparticles were confirmed as 283.2 ± 16 nm, –31.2 ± 6.8 mV, 63.1 ± 4.2%, and 6.14 ± 0.3 h, respectively. The hydrogel containing 3% w/v CTS/CS nanoparticles existed as a solution with low viscosity at room temperature converted to a semisolid upon increasing the temperature to 35 °C. Hydrogel engrafted with CTS/CS showed controlled release of RSV during 48 h with superior in vitro gel stability. As revealed by cytotoxicity and mineralization assays, incorporation of RSV-loaded particles into PF127/HA hydrogel led to improvement in osteoblast viability and proliferation.

FORMULATION AND OPTIMIZATION OF THERMOSENSITIVE IN-SITU GEL OF MOXIFLOXACIN HYDROCHLORIDE FOR OCULAR DRUG DELIVERY

Objective: The present study has focused on development and optimization of thermosensitive in-situ ocular drug delivery system for the treatment of conjunctivitis.Methods: Thermosensitive in-situ hydrogel formulation of moxifloxacin hydrochloride was developed by dispensing variable concentration of pluronic F-127, gellan-gum, and carbopol in distilled water. Viscosity, gelation temperature and mean release time (MRT) were measured by using ‘Brookfield' viscometer LV-III (spindle no. 40), rheological techniques and dissolution apparatus respectively. Optimization for ideal formulation was carried by ‘Box–Behnken' design on the basis of prime factors of the formulation including viscosity, gelation temperature, and MRT. Moreover, the optimized formulation was evaluated for accelerated stability study by in vitro drug release, anti-microbial potential by ‘Kirby-Bauer disk diffusion' method and ocular irritancy assay were done by in vivo analysis.Results: Optimised thermosensitive in-situ gel, when administered into cul-de-sac region of the eye, it was immediately transformed from sol to gel by multi-dimensional mechanism due to plurionic, gellan-gum, carbopol. The optimized formulation minimizes the chances of formulation failure as well as the concentration on individual polymer which dependence on a single mechanism of gelation. The final optimised formulation consists of plurionic (11.50% w/v), gellan-gum (0.32% w/v), carbopol (0.3% w/v), shows optimum therapeutic effect. Moreover, the accelerated stability study, anti-microbial potential, and ocular irritancy confirmed the biocompatibility of optimized in-situ drug-containing gel with high potency and stability.Conclusion: Thus, optimized in-situ drug-containing gel with multifactorial approaches showed promising ocular formulation having minimum side effect and high therapeutic efficacy.Â

Influence of formulation parameters on encapsulation and release characteristics of curcumin loaded in chitosan-based drug delivery carriers

Drugs derived from plants with excellent chemotherapeutic effectiveness and relatively low toxicity may fail to scale through the phyto-drug discovery channel due to lack of appropriate drug delivery systems. These phytoceuticals need compatible carriers that will improve their stability, bioavailability and enhance their effectiveness. In this study, chitosan-based drug delivery carriers (DDCs) containing curcumin as phyto-drug model were prepared either via ionotropic gelation with tripolyphosphate or polyelectrolyte complexation with alginate. Influence of formulation parameters was evaluated using encapsulation and release characteristics as response indices. Crosslinking time, pH of chitosan solution and concentration of curcumin, alginate or tripolyphosphate significantly influenced the encapsulation efficiency, rate of curcumin release and mean release time (MRT) in simulated gastric fluid (SGF). Roughly spherical chitosan-based micro-beads with copious pores within the matrix and of improved encapsulation efficiency (82–93%) were prepared using optimized set of formulation parameters. Incorporation of alginate into the chitosan DDC reduced erosion of curcumin by 30% and extended MRT by 180 min in SGF without net delineating change in release profiles of curcumin in simulated physiological saline and intestinal fluids. Time-dependent in vitro study showed that radical scavenging activity ratio of curcumin was enhanced via encapsulation in chitosan-based DDCs.

PLGA-PEG-RA-based polymeric micelles for tumor targeted delivery of irinotecan

To develop an effective therapeutic treatment, the potential of poly (lactic-co-glycolic acid)-polyethylene glycol-retinoic acid (PLGA-PEG-RA) polymeric micelles for targeted delivery of irinotecan to hepatocellular carcinoma (HepG2) and colorectal cancer cell lines (HT-29) was evaluated. PLGA-PEG-RA was synthesized by amide reaction of PLGA with NH2–PEG–NH2 and then PLGA-PEG-NH2 with RA and confirmed by FTIR and 1H NMR spectroscopy. Irinotecan-loaded nanomicelles were prepared using thin-film hydration method and the impact of various formulation variables on their particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), and mean release time (MRT) were assessed using a Taguchi design. TEM was used to observe morphology of the nanomicelles and the CMC was determined by fluorescence spectroscopy. Adopted PLGA-PEG-RA nanomicelle exhibited PS of 160 ± 9.13 nm, PDI of 0.20 ± 0.05, ZP of −24.9 ± 4.03 mV, EE of 83.9 ± 3.61%, MRT of 3.28 ± 0.35 h, and CMC value of 25.7 μg/mL. Cytotoxicity of the targeted nanomicelles on HepG2 and HT-29 cell lines was significantly higher than that of non-targeted nanomicelles and the free drug. These results suggest that PLGA-PEG-RA nanomicelles could be an efficient delivery system of irinotecan for targeted therapy of colorectal cancer and hepatocellular carcinoma.

Encapsulation in chitosan-based polyelectrolyte complexes enhances antidiabetic activity of curcumin

Low bioavailability, poor aqueous stability and lack of appropriate delivery systems delimit the chemotherapeutic effect of curcumin. In this study, curcumin was encapsulated in chitosan-based polyelectrolyte complexes and its antidiabetic activities were assessed using in vitro α-amylase inhibitory assay and in vivo antihyperglycaemic effect in alloxan-induced rats. Microscopic examination showed nanoformulations (<50nm) of curcumin loaded in chitosan-alginate complex. Improved encapsulation efficiency (64–76%), loading capacity (20–26%) and yield (50–72%) were achieved. Complexation of chitosan with alginate reduced loss of curcumin by 20% and extended mean release time by 40min in simulated gastric fluid. Time dependent study showed that the α-amylase inhibitory activity of curcumin was enhanced via nanoencapsulation. Oral administration of sub-therapeutic dosage of curcumin (50mg/kg b.wt.) nanoencapsulated in chitosan-based complexes caused significant reduction in hyperglycaemia within 7days of treatment. Overall, chemotherapeutic effectiveness of curcumin was enhanced via nanoencapsulation in chitosan-based polyelectrolyte complexes.

Development and optimization of transferrin-conjugated nanostructured lipid carriers for brain delivery of paclitaxel using Box–Behnken design

The treatment of brain cancer remains one of the most difficult challenges in oncology. The purpose of this study was to develop transferrin-conjugated nanostructured lipid carriers (Tf-NLCs) for brain delivery of paclitaxel (PTX). PTX-loaded NLCs (PTX-NLCs) were prepared using solvent evaporation method and the impact of various formulation variables were assessed using Box–Behnken design. Optimized PTX-NLC was coupled with transferrin as targeting ligand and in vitro cytotoxicity of it was investigated against U-87 brain cancer cell line. As a result, 14.1 mg of cholesterol, 18.5 mg of triolein, and 0.5% poloxamer were used to prepare the optimal formulation. Mean particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug loading (DL), mean release time (MRT) of adopted formulation were confirmed to be 205.4 ± 11 nm, 25.7 ± 6.22 mV, 91.8 ± 0.5%, 5.38 ± 0.03% and 29.3 h, respectively. Following conjugation of optimized PTX-NLCs with transferrin, coupling efficiency was 21.3 mg transferrin per mmol of stearylamine; PS and MRT were increased while ZP, EE and DL decreased non-significantly. Tf-PTX-NLCs showed higher cytotoxic activity compared to non-targeted NLCs and free drug. These results indicated that the Tf-PTX-NLCs could potentially be exploited as a delivery system in brain cancer cells.

Added release time in diffusion/dissolution coupled release

While increasingly sophisticated models have been developed to more accurately predict dispersed solute release from complex systems, distillation of their results into quantitative trends has been difficult. Here, the numerically calculated release profiles of coupled diffusion/dissolution systems are quantified by their cumulative release time (CRT) and compared against corresponding diffusion-controlled limits. The increase in CRT due to a finite dissolution rate was found to vary inversely with the second Damköhler number across several orders of magnitude, and also vary linearly with the amount of solid drug loaded in the system. The analytical nature of the relationship provides new physical insights into the system and appears to be indifferent to the form of the secondary rate-limiting step. This work provides a simple analytical expression with which one can not only predict the mean release time for a given set of parameter values, but understand precisely how each parameter value will affect it. The simplicity of the correlation and the lack of apparent limits to its validity also suggest the existence of an analytical pathway for its derivation, which may yield additional insights into the effect of secondary rate processes on controlled release.

Controlling antibiotic release from mesoporous silica nano drug carriers via self-assembled polyelectrolyte coating.

Mesoporous silica nanoparticles (MSNs) have been explored as controlled drug delivery systems since the early 2000s, but many fundamental questions remain for this important application. We sought to design a pH controlled delivery system of gentamicin, an aminoglycoside antibiotic, based on MSNs. Under optimal conditions, MSN was able to load 219µg gentamicin per mg MSNs. Polymeric networks encompassing gentamicin loaded MSNs were then established to tune the release kinetics. Embedding of drug pre-loaded MSNs was performed by an efficient layer-by-layer (LbL) self-assemble strategy using polystyrene sulfonate (PSS) and poly (allylamine hydrochloride) (PAH). We characterised the release kinetics by nonlinear mixed-effects modelling in the S-ADAPT software. The mean release time from uncoated MSNs was 3.6days at pH 7.4 and 0.4days at pH 1.4. A further slower release was achieved by diffusion through one or two PSS/PAH bilayer(s) which had a mean transit time of 6.0days at pH 7.4 and 3.5days at pH 1.4. The number of bilayers affected the shape of the release profile. The developed nano-drug carriers combined with the self-assembled polyelectrolyte coating allowed us to tune the release kinetics by pH and the number of bilayers.

Applying the Taguchi design for optimized formulation of sustained release gliclazide chitosan beads: an in vitro/in vivo study.

Gliclazide is a second generation of hypoglycemic sulfonylurea and acts selectively on pancreatic beta cell to control diabetes mellitus. The objective of this study was to produce a controlled release system of gliclazide using chitosan beads. Chitosan beads were produced by dispersion technique using tripolyphosphate (TPP) as gelating agent. The effects of process variables including chitosan molecular weight, concentration of chitosan and TPP, pH of TPP, and cross-linking time after addition of chitosan were evaluated by Taguchi design on the rate of drug release, mean release time (MRT), release efficiency (RE(8)%), and particle size of the beads. The blood glucose lowering effect of the beads was studied in normal and streptozotocin-diabetic rats. The optimized formulation CL(2)T(5)P(2)t(10) with about 31% drug loading, 2.4 h MRT, and 69.16% RE(8)% decreased blood glucose level in normal rats for 24 h compared to pure powder of gliclazide that lasted for just 10 h.