Proniosomal gel-mediated transdermal delivery of bromocriptine: in vitro and ex vivo evaluation

Vesicular systems endow large opportunities for the transdermal delivery of therapeutics. The present study was designed to investigate the potential of a novel class of vesicular system ‘proniosome’ as a carrier for transdermal delivery of bromocriptine (BCT). Proniosome formulations were prepared by the coacervation-phase separation method and the influence of factors like surfactant type and its amount, lipid concentration, cholesterol amount and drug content were studied. Span 60 was the most appropriate surfactant, and yielded vesicle size and percentage encapsulation efficiency of 1.3 µm and 98.9%, respectively. The developed system was characterised w.r.t. morphology, transition temperature, drug release, skin permeation and skin irritancy. Proniosomes exhibited a sustained release pattern of BCT in vitro. Skin permeation study revealed high penetration of proniosomes with sustained release of BCT through rat skin. The optimised proniosomal formulation showed enhanced transdermal flux of 16.15 μg/cm²/h as compared to 3.67 μg/cm²/h for drug dispersion. The developed formulations were observed as non-irritant to the rat skin and were found as quite stable at 4 and 25 °C for 90 days w.r.t. vesicle size and drug content. The dried proniosomal formulation could act as a promising alternative to niosomes and preferably for transdermal delivery of BCT.     

Preparation and evaluation of optimized zolmitriptan niosomal emulgel

Objective: Novel niosomal formulation may be successfully applied to treat a systemic disease such as migraine through transdermal drug delivery system (TDDS), moreover, the treatment of topical diseases such as mycotic infections by targeting and localizing the drug to the stratum corneum. The current study aims to formulate zolmitriptan (Zt) in niosomal vesicles to potentiate its transdermal effect.

Significance: The development of a promising niosomal formulation will push the scaling up of pharmaceutical industry in this field.

Methods: Design- Expert 10 was used to design twelve formulations using Box-Behnken. Zt loaded niosomes were prepared by the thin film hydration method using Span 60(S 60), Span 80(S 80) along with cholesterol(Ch) at three different levels. The optimized formulation (F11) was formulated in Emulgel (1:1 emulsion/gel ratio).

Results: The vesicles revealed vesicle size (VS) ranging from 133.1 to 851.3?nm, zeta potential (ZP) ?43.8 to ?82.8?mV, entrapment efficiency (EE%) from 66.7 to 88.7%, and Zt release after 4?h up to 67%. Optimized niosomal formulation (F11) depicted the smallest VS (133.1?nm), highest EE (88.7%), high ZP (?80.6?mV) and satisfactory release after 4?h (61.5%). There was a significant difference (p <.05) in drug permeation after 8?h for niosomal F11(460.98?ug/cm²) and niosomal F11 loaded Emulgel (336.92?ug/cm²) compared to plain Zt loaded emulgel (160.83?ug/cm²). Niosomal F11 loaded emulgel showed thixotropic behavior of rapid recovery, significant bioavailability and pharmacokinetic parameters as compared to the plain Zt-loaded Emulgel.

Conclusion: Optimized F11 represents a promising formulation for transdermal drug delivery system to treat both topical and systemic diseases.     

Sustained release of piroxicam from solid lipid nanoparticle as an effective anti-inflammatory therapeutics in vivo

Abstract

This study aims to investigate the solid lipid nanoparticle (SLN) as a novel vehicle for the sustained release and transdermal delivery of piroxicam, as well as to determine the anti-inflammation effect of piroxicam-loaded SLN. SLN formulation was optimized and the particle size, polydispersity index, zeta potential (ZP), encapsulation efficiency, drug release, and morphological properties were characterized. The transdermal efficiency and mechanism of the piroxicam-loaded SLNs were investigated in vitro. With the inflammation induced edema model in rat, the anti-inflammatory efficiency of piroxicam-enriched SLNs (Pir-SLNs) was evaluated. The SLN formulation was optimized as: lecithin 100?mg, glycerin monostearate 200?mg, and Tween (1%, w/w). The particle size is around 102?±?5.2?nm with a PDI of 0.262. The ZP is 30.21?±?2.05?mV. The prepared SLNs showed high entrapment efficiency of 87.5% for piroxicam. There is no interaction between piroxicam and the vehicle components. The presence of polymorphic form of lipid with higher drug content in the optimized Pir-SLNs enables the Pir-SLNs to release the drug with a sustained manner. Pir-SLNs with oleic acid as enhancer can radically diffuse into both the stratum corneum and dermal layer, as well as penetrate through the hair follicles and sebaceous glands with significantly higher density than the other control groups. Pir-SLNs promptly inhibited the inflammation since the 3rd hour after the treatment by decreasing the PGE₂ level. SLN was demonstrated to be a promising carrier for encapsulation and sustained release of piroxicam. Pir-SLN is a novel topical preparation with great potential for anti-inflammation application.     

Transdermal delivery of alprazolam from a monolithic patch: formulation based on in vitro characterization

Alprazolam, a benzodiazepine widely used for the treatment of psychiatric disorders, has been aimed to be formulated in a transdermal delivery system (TDS) prototype. A series of TDS prototypes dosed in all cases at 0.35 mg·cm^?2 of alprazolam were prepared as a monolithic drug in adhesive matrix using acrylic pressure-sensitive adhesives (PSA) of acrylate vinyl acetate (Duro-tack^®). The effects of several permeation enhancers as azone, transcutol, propylene glycol, dodecyl alcohol, decyl alcohol, diethanolamine, N-methyl pyrrolidone and lauric acid were studied. Prototypes have been characterized based on adhesion parameters (peel adhesion and shear adhesion), in vitro human skin permeation and in vitro drug release according to European Pharmacopoeia for the selected prototype. Best results show that a combination of permeation enhancers from different chemical groups is able to provide almost a 33 fold increase in the transdermal alprazolam flux of an aqueous saturated dispersion (from 0.054?±?0.019 to 1.76?±?0.21 μg h.cm^?2). Based on these in vitro flux data, a predictive simulation of the achievable plasmatic levels was performed assuming a constant systemic infusion of drug. In summary, it is possible to obtain a prototype of a TDS of alprazolam with adequate adhesive properties (peel adhesion and shear adhesion) and able to predict sustained therapeutic plasmatic levels.     

Enhanced oral bioavailability of 10-hydroxycamptothecin through the use of poly (n-butyl cyanoacrylate) nanospheres

The article describes the preparation, physicochemical characterization, drug release, and in vivo behavior of 10-hydroxycamptothecin-loaded poly (n-butyl cyanoacrylate) (PBCA) nanospheres (HCPT-PBCA-NSs). HCPT-PBCA-NSs were successfully prepared via emulsion polymerization of n-butyl cyanoacrylate (BCA) monomer in acidic medium with the aid of two colloidal stabilizers (Poloxamer 188 and Dextran 70). The influence of pH, the time of polymerization, and the dosage of the drug on particle size and encapsulation efficiency (EE) were studied. HCPT-PBCA-NSs were of spherical shape and uniformly dispersed with a particle size of 135.7?nm, and zeta potential of ?18.18?mV. EE, drug loading (DL), and yield of HCPT-PBCA-NSs were 51.52, 0.63, and 88.25%, respectively. FTIR, ¹H NMR, and DSC showed complete polymerization of BCA monomer and HCPT existed in the form of molecular or amorphous in NSs. In vitro release of the drug from HCPT-PBCA-NSs exhibited sustained-release behavior with an initial burst release and about 60% of HCPT was released from the formulation within 24?h of dialysis. The pharmacokinetic study in healthy rats after oral administration showed that encapsulation of HCPT into PBCA-NSs increased the C_max about 3.84 times and increased AUC_0?t about 5.40 times compared with that of HCPT suspension. It was concluded that PBCA-NSs could be a promising drug carrier to load HCPT for oral drug delivery if efforts are made in the future to improve its poor DL capacity.     

Nanovesicular carrier-mediated transdermal delivery of tadalafil: i- formulation and physicsochemical characterization

The limited permeability of stratum corneum, the main skin barrier, towards pharmaceutical active ingredients represents the main obstacle encounter the transdermal drug delivery system. In the current study, penetration enhancer-containing nanoliposomes, that is, penetrosomes were formulated incorporating tadalafil to enhance its transdermal permeability. Hydration-sonication method was used to prepared penetrosomes bearing tadalafil. The prepared nanocarriers were characterized in terms of vesicles shape and surface morphology, size and size distribution, zeta potential, entrapment efficiency, and elasticity. Results pointed to that penetrosomes were spherical in shape with a unilamellar-closed structure in the nanometric narrow size range proved by their law span index. Penetrosomes formulations elaborated deformable vesicles more than the conventional liposomes, with the Penetrosomes-based Labrasol® being the most deformable formulation. Penetrosomes-ultraelastic nanoliposomes represent an attractive vehicle for transdermal delivery of tadalafil to treat erectile dysfunction.     

Transdermal delivery of alprazolam from a monolithic patch: formulation based on in vitro characterization

Alprazolam, a benzodiazepine widely used for the treatment of psychiatric disorders, has been aimed to be formulated in a transdermal delivery system (TDS) prototype. A series of TDS prototypes dosed in all cases at 0.35 mg·cm(-2) of alprazolam were prepared as a monolithic drug in adhesive matrix using acrylic pressure-sensitive adhesives (PSA) of acrylate vinyl acetate (Duro-tack(?)). The effects of several permeation enhancers as azone, transcutol, propylene glycol, dodecyl alcohol, decyl alcohol, diethanolamine, N-methyl pyrrolidone and lauric acid were studied. Prototypes have been characterized based on adhesion parameters (peel adhesion and shear adhesion), in vitro human skin permeation and in vitro drug release according to European Pharmacopoeia for the selected prototype. Best results show that a combination of permeation enhancers from different chemical groups is able to provide almost a 33 fold increase in the transdermal alprazolam flux of an aqueous saturated dispersion (from 0.054?±?0.019 to 1.76?±?0.21 μg h.cm(-2)). Based on these in vitro flux data, a predictive simulation of the achievable plasmatic levels was performed assuming a constant systemic infusion of drug. In summary, it is possible to obtain a prototype of a TDS of alprazolam with adequate adhesive properties (peel adhesion and shear adhesion) and able to predict sustained therapeutic plasmatic levels.     

Development and evaluation of nanosized niosomal dispersion for oral delivery of Ganciclovir

Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to enhance the oral absorption and prolong the existence of the drug in the systemic circulation. So the purpose of the present study was to improve the oral bioavailability of Ganciclovir by preparing nanosized niosomal dispersion. Niosomes were prepared from Span40, Span60, and Cholesterol in the molar ratio of 1:1, 2:1, 3:1, and 3:2 using reverse evaporation method. The developed niosomal dispersions were characterized for entrapment efficiency, size, shape, in vitro drug release, release kinetic study, and in vivo performance. Optimized formulation (NG8; Span60:Cholesterol 3:2 molar ratio) has shown a significantly high encapsulation of Ganciclovir (89?±?2.13%) with vesicle size of 144?±?3.47?nm (polydispersity index [PDI]?=?0.08). The in vitro release study signifies sustained release profile of niosomal dispersions. Release profile of prepared formulations have shown that more than 85.2?±?0.015% drug was released in 24?h with zero-order release kinetics. The results obtained also revealed that the types of surfactant and Cholesterol content ratio altered the entrapment efficiency, size, and drug release rate from niosomes. In vivo study on rats reveals five-time increment in bioavailability of Ganciclovir after oral administration of optimized formulation (NG8) as compared with tablet. The effective drug concentration (>0.69 µg/mL in plasma) was also maintained for at least 8?h on administration of the niosomal formulation. In conclusion, niosomes can be proposed as a potential oral delivery system for the effective delivery of Ganciclovir.     

Formulation design and optimization of novel soft glycerosomes for enhanced topical delivery of celecoxib and cupferron by Box–Behnken statistical design

Background: The present study describes glycerosomes (vesicles composed of phospholipids, glycerol and water) as a novel drug delivery system for topical application of celecoxib (CLX) and cupferron (CUP) compound.

Aim: The goal of this research was to design topical soft innovative vesicles loaded with CLX or CUP for enhancing the efficacy and avoiding systemic toxicity of CLX and CUP.

Methods: CLX and CUP loaded glycerosomes were prepared by hydrating phospholipid-cholesterol films with glycerol aqueous solutions (20–40%, v/v). Box–Behnken design, using Design-Expert® software, was the optimum choice to statistically optimize formulation variables. Three independent variables were evaluated: phospholipid concentration (X₁), glycerol percent (X₂) and tween 80 concentration (X₃). The glycerosomes particle size (Y₁), encapsulation efficiency percent (Y₂: EE %) and drug release (Y₃) were selected as dependent variables. The anti-inflammatory effect of CLX and CUP glycerosomal gel was evaluated by carrageenan-induced rat paw edema method followed by histopathological studies.

Results: The optimized formulations (CLX2* and CUP1*) showed spherical morphology under transmission electron microscopy, optimum particle size of 195.4?±?3.67?nm, 301.2?±?1.75?nm, high EE of 89.66?±?1.73%, 93.56?±?2.87%, high drug release of 47.08?±?3.37%, 37.60?±?1.89% and high cumulative amount of drug permeated in 8?h of 900.18?±?50.24, 527.99?±?34.90?µg.cm^?2 through hairless rat skin, respectively. They also achieved significant remarkable paw edema inhibition in comparison with the control group (p? Conclusion: Finally, the administration of CLX2* and CUP1* loaded glycerosomal gel onto the skin resulted in marked reduction of edema, congestive capillary and inflammatory cells and this approach may be of value in the treatment of different inflammatory disorders.     

Formulation and optimization of intranasal nanolipid carriers of pioglitazone for the repurposing in Alzheimer’s disease using Box-Behnken design

Growing evidence suggest that Alzheimer’s disease (AD), the most common cause of dementia among the elderly is a metabolic disorder associated with impaired brain insulin signaling. Hence, the diabetic drug can be a therapeutic option for the management AD. The researches in this area are ongoing and Pioglitazone (PIO) is one of the most investigated diabetic drug in AD. Eventhough PIO treatment was found to improve AD significantly in the preclinical models, the poor blood-brain barrier (BBB) permeability and serious peripheral side effects limited its success in the clinical trials. The objective of the present study was to formulate and optimize intranasal (IN) nano lipid carriers (NLC) of PIO for its targeted delivery to the brain. A Box-Behnken design was employed to optimize the effect of three independent variables on two dependent variables. The optimized formulation had a particle size (PS) of 211.4?±?3.54?nm and zeta potential of (ZP) of 14.9?±?1.09?mv. The polydispersibility index (PDI) and entrapment efficiency (EE) was found to be 0.257?±?0.108 and 70.18?±?4.5% respectively. Storage stability studies performed has confirmed the stability of NLCs at 4?°C and 25?°C. The in-vitro drug release study has exhibited a sustained release of drug from the NLC. The formulation was observed to improve the nasal permeability of PIO ex-vivo significantly. Toxicity studies were performed to confirm the safety of formulation for the in-vivo administration. In-vivo biodistribution study in rats has shown a direct transport of drug from the nose to brain from the IN-NLC.     

Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation,characterization, plasma,and kidney pharmacokinetics

The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6?±?5.95?nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71?±?3.02%, and the drug loading was 1.56?±?0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUC_kidney/AUC_plasma?=?0.586?±?0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.     

Preparation,characterization, and pharmacokinetics study of a novel genistein-loaded mixed micelles system

Genistein (GEN), is a natural dietary isoflavone, has been reported to show anticancer activities. However, its poor aqueous solubility and oral bioavailability limit its clinical application. We designed a novel genistein-loaded mixed micelles (GEN-M) system composed of Soluplus^® and Vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared by organic solvent evaporation aimed to overcome the challenges of GEN’s poor solubility and then further improve its oral bioavailability. The optimized, spherical-shaped GEN-M was obtained at a ratio of 10:1 (Soluplus^®:TPGS). The mean particle size of GEN-M was 184.7?±?2.8?nm, with a narrow polydispersity index (PDI) of 0.162?±?0.002. The zeta potential value of GEN-M was ?2.92?±?0.01?mV. The micelles solutions was transparent with blue opalescence has high the entrapment efficiency (EE) and drug loading (DL) of 97.12?±?2.11 and 3.87?±?1.26%, respectively. GEN-M was demonstrated a sustained release behavior when formed micelles shown in drug release in vitro. The solubility of GEN in water increased to 1.53?±?0.04?mg/mL after encapsulation. The permeability of GEN across a Caco-2 cell monolayer was enhanced, and the pharmacokinetics study of GEN-M showed a 2.42-fold increase in relative oral bioavailability compared with free GEN. Based on these findings, we conclude that this novel nanomicelles drug delivery system could be leveraged to deliver GEN and other hydrophobic drugs.     

Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling,characterization, and ex vivo skin permeation

Objective: The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience.

Methods: TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3?×?2²-level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (Y₁), vesicle size (Y₂), polydispersity index (Y₃), and zeta potential (Y₄) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug–excipient interactions, and vesicle stability were also investigated.

Results: The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (p?Conclusion: The study suggests the applicability of statistical modeling as a promising tool for prediction of ethosomal characteristics. The ethanolic vesicles were considered as novel potential nanocarriers for accentuated transdermal TRO delivery.     

Preparation of alginate oligosaccharide nanoliposomes and an analysis of their inhibitory effects on Caco‐2 cells

The conditions were optimised for preparing Alginate oligosaccharide (AOS) nanoliposomes, and Caco‐2 cell experiments were carried out to examine their antitumour effects. The optimal formulation of AOS nanoliposomes was as follows: a phosphatidylcholine‐to‐cholesterol ratio of 5.12, AOS concentration of 8.44 mg/mL, Tween 80 concentration of 1.11%, and organic phase to aqueous phase ratio of 5.25. Under the above conditions, the experimental encapsulation efficiency was 65.84%, and the AOS nanoliposomes exhibited a small particle size of 323 nm. After Caco‐2 cells were treated with AOS liposomes and AOS for 24 h, AOS nanoliposomes inhibited the growth of Caco‐2 cells to a greater extent than AOS at concentrations of 0.0625, 0.125, 0.25, 0.5 and 1 mg/mL (P  <  0.01). LDH leakage exhibited a concentration‐dependent increase following treatment with 0.5‐1 mg/mL AOS nanoliposomes, and the inhibitory effect of AOS nanoliposomes exhibited a more significant difference than AOS (P  <  0.01). Cells treated with 0.5 mg/mL and 1 mg/mL AOS nanoliposomes displayed a substantial and significant increase in activity compared with AOS (P  < 0.01). Based on these results, AOS nanoliposomes exerted a more significant effect on inhibiting Caco‐2 cell proliferation than AOS.Inspec keywords: evaporation, cellular biophysics, biomedical materials, biomembranes, nanomedicine, enzymes, biochemistry, drug delivery systems, particle size, response surface methodology, molecular biophysics, encapsulation, drugs, lipid bilayers, nanofabrication, materials preparation, polymers, nanostructured materialsOther keywords: reverse‐phase evaporation method, response surface methodology, alginate oligosaccharide nanoliposomes, mitochondrial function, AOS concentration, AOS liposomes, Caco‐2 cell proliferation, AOS nanoliposomes, methyl thiazolyl tetrazolium assay, cell counting kit‐8, lactate dehydrogenase, LDH assay, phosphatidylcholine‐to‐cholesterol ratio, size 323.0 nm, time 24.0 hour     

Preparation and evaluation of self-assembly Soluplus®-sodium cholate-phospholipid ternary mixed micelles of docetaxel

Abstract

Ternary mixed micelles constituted of Soluplus^®, sodium cholate, and phospholipid were prepared as nano-delivery system of the anticancer drug, docetaxel. The formulation of docetaxel-loaded ternary mixed micelles (DTX-TMMs) with an optimized composition (Soluplus^®/sodium cholate/phospholipid= 3:2:1 by weight) were obtained. The main particle size of DTX-TMMs was 76.36?±?2.45?nm, polydispersity index (PDI) was 0.138?±?0.039, and the zeta potential was ?8.46?±?0.55?mv. The encapsulation efficiency was 94.24?±?4.30% and the drug loading was 1.25%. The critical micelle concentration value was used to assess the ability of carrier materials to form micelles. The results indicated that the addition of Soluplus^® to sodium cholate-phospholipid mixed micelles could reduce the critical micelle concentration and improve the stability. In vitro release studies demonstrated that compared with DTX-Injection group, the DTX-TMMs presented a controlled release property of drugs. In vivo pharmacodynamics results suggested that DTX-TMMs had the most effective inhibitory effect on tumor proliferation and had good biosafety. In addition, the relative bioavailability of mixed micelles was increased by 1.36 times compared with the DTX-Injection in vivo pharmacokinetic study indicated that a better therapeutic effect could be achieved. In summary, the ternary mixed micelles prepared in this study are considered to be promising anticancer drug delivery systems.     

Improved oral bioavailability of valsartan using proliposomes: design,characterization and in vivo pharmacokinetics

Abstract

The objective of our investigational work was to develop a proliposomal formulation to improve the oral bioavailability of valsartan. Proliposomes were formulated by thin film hydration technique using different ratios of phospholipids:drug:cholesterol. The prepared proliposomes were evaluated for vesicle size, encapsulation efficiency, morphological properties, in vitro drug release, in vitro permeability and in vivo pharmacokinetics. In vitro drug-release studies were performed in simulated gastric fluid (pH 1.2) and purified water using dialysis bag method. In vitro drug permeation was studied using parallel artificial membrane permeation assay (PAMPA), Caco-2 monolayer and everted rat intestinal perfusion techniques. In vivo pharmacokinetic studies were conducted in male Sprague Dawley (SD) rats. Among the proliposomal formulations, F-V was found to have the highest encapsulation efficiency of 95.6?±?2.9% with a vesicle size of 364.1?±?14.9?nm. The in vitro dissolution studies indicated an improved drug release from proliposomal formulation, F-V in comparison to pure drug suspension in both, purified water and pH 1.2 dissolution media after 12?h. Permeability across PAMPA, Caco-2 cell and everted rat intestinal perfusion studies were higher with F-V formulation as compared to pure drug. Following single oral administration of F-V formulation, a relative bioavailability of 202.36% was achieved as compared to pure valsartan.     

Implementation of two different experimental designs for screening and optimization of process parameters for metformin-loaded carboxymethyl chitosan formulation

Abstract

Metformin (MET) was effectively encapsulated into O-carboxymethyl chitosan (O-CMC) polymeric formulation using an experimental design method. Six factors Plackett–Burman (PB) design was utilized to find the significant process parameters. Linear equations used to study the effect of each process parameters on particle size (PS), encapsulation efficiency (EE), and zeta potential (ZP) and the most influential three factors decided for further optimization. Optimization was carried out by implementing three-factor three-level Box–Behnken (BB) design. Mathematical models were generated by regression analysis for responses of PS, EE, and ZP. Two-step experimental design took into account for the preparation of optimized formulation with maximum %EE (72.78?±?9.7%) and minimum PS (225.67?±?5.53?nm) at optimum process conditions with a ZP of –5.22?mV for the nano-polymeric formulation in an economical matter by reduction chemical use and formulation time. Furthermore, the biological activity of the final formulation was determined by in vitro cytotoxicity study compared to free MET. The cytotoxicity result reveals that both pure drug and nano-formulation biocompatible with MCF10A non-tumorigenic cell line and lethal for the MCF7 cell line. These in vitro results were the first helpful step to further investigate O-CMC loaded MET nanoparticles in diagnostic and therapeutic applications of breast cancer.     

Formulation and corneal permeation of ketorolac tromethamine-loaded chitosan nanoparticles

Abstract

The aim of this work was to formulate chitosan (CS)-based nanoparticles (NPs) loaded with ketorolac tromethamine (KT) intended for topical ocular delivery. NPs were prepared using ionic gelation method incorporating tri-polyphosphate (TPP) as cross-linker. Following the preparation, the composition of the system was optimized in terms of their particle size, zeta potential, entrapment efficiency (EE) and morphology, as well as performing structural characterization studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The data suggested that the size of the NPs was affected by CS/TPP ratio where the diameter of the NPs ranged from 108.0?±?2.4?nm to 257.2?±?18.6?nm. A correlation between drug EE and the corresponding drug concentration added to the formulation was observed, where the EE of the NPs increased with increasing drug concentration, for up to 10?mg/mL. FT-IR and DSC revealed that KT was dispersed within the NPs where the phosphate groups of TPP were associated with the ammonium groups of CS. The in vitro release profile of KT from CS NPs showed significant differences (p?<?0.05) compared to KT solution. Furthermore, mucoadhesion studies revealed adhesive properties of the formulated NPs. The KT-loaded NPs were found to be stable when stored at different storage conditions for a period of 3 months. The ex vivo corneal permeation studies performed on excised porcine eye balls confirmed the ability of NPs in retaining the drug on the eye surface for a relatively longer time. These results demonstrate the potential of CS-based NPs for the ocular delivery of KT.     

Study of physicochemical properties of flutamide-loaded Ocimum basilicum microspheres with ex vivo mucoadhesion and in vitro drug release

Drug which shows extensive first pass effect is difficult task that, needs to be solved by formulators in the pharmaceutical science. The low oral bioavailability (49%) of flutamide may be due to poor wettability, low aqueous solubility and extensive first pass effect. The aim of present investigation was to prepare flutamide loaded microspheres and incorporate it into suppositories for rectal delivery to avoid first pass effect and enhance residence time. Flutamide loaded mucoadhesive microspheres of Ocimum Basilicum mucilage (OBM) were prepared using spray drying and characterized by percent production yield, encapsulation efficiency, particle size, zeta potential, polydispersity index, DSC, SEM, XRPD, in vitro drug release and stability studies. Moreover, ex vivo mucoadhesion was investigated using falling liquid film technique to determine the adhesion of microspheres to sheep rectal mucosa. The microspheres had nearly spherical shape and size about 2.53?μm. The encapsulation efficiency and mucoadhesion of optimized formulation MBF10 were found to be 69.6?±?2.3% and 89.01?±?2.18%, respectively. Percent CDR of optimized flutamide loaded mucoadhesive microspheres was found to be 88.7?±?1.3 at 7?h. In conclusion, OBM microparticles based suppository could be used to deliver drug through rectal delivery.     

Impact of surfactant selection on the formulation and characterization of microparticles for pulmonary drug delivery

The effect of suspension stabilizers, internal aqueous phase volume and polymer amount were investigated for the production of protein loaded poly(d,l?lactide-co-glycolide) (PLGA) microparticles suitable for pulmonary drug delivery. PLGA microparticles were produced adopting water-in-oil-in-water (W/O/W) solvent evaporation technique and were investigated for surface morphology, particle size, encapsulation efficiency (EE%) and in-vitro release profile. Porous surface morphologies with a narrow size distribution were observed when employing 0.5?ml internal aqueous phase; 23.04?µm (±0.98), 15.05?µm (±0.27) and 22.89?µm (±0.41) for PVA, Tween 80 and oleic acid. Porous microparticles exhibited increased size and reduction in EE% with increasing internal aqueous phase, with non-porous microparticles produced when adopting 2.0?ml internal aqueous phase. The selection of stabilizer influences the size of the pores formed thus offers potential for the aerodynamic properties of the microparticles to be manipulated to achieve suitable aerosolization characteristics for pulmonary delivery of proteins.