Breaking barriers: bilosomes gel potentials to pave the way for transdermal breast cancer treatment with Tamoxifen.

OBJECTIVE: Breast cancer affects women globally, regardless of age or location. On the other hand, Tamoxifen (TXN), a class II biopharmaceutical drug is acting as a prophylactic/treating agent for women at risk of and/or with hormone receptor-positive breast cancer. However, its oral administration has life-threatening side effects, which have led researchers to investigate alternative delivery methods. One such method is transdermal drug delivery utilizing bile salts as penetration enhancers, aka Bilosomes. METHODS: Bilosomes formulations were optimized statistically for the outcome of vesicle shape, size, and entrapment efficiency using two types of bile, i.e. sodium taurocholate and sodium cholate. These bilosomes were then loaded into HPMC base gel and further characterized for their morphology, drug content, pH, viscosity, spreadability and eventually ex-vivo skin penetration and deposition studies. RESULTS: Findings showed that sodium cholate has superiority as a penetration enhancer over sodium taurocholate in terms of morphological characterizes, zeta potential, and cumulative amounts of tamoxifen permeated per unit area (15.13 ± 0.71 µg/cm2 and 6.51 ± 0.6 µg/cm2 respectively). In fact, bilosomes designed with sodium cholate provided around 9 folds of skin deposition compared to TXN non-bilosomal gel. CONCLUSION: Bilosomes gels could be a promising option for locally delivering tamoxifen to the breast through the skin, offering an encouraging transdermal solution.

An RP-HPLC-UV method with SPE for cefotaxime in all-in-one total parenteral nutritional admixtures: application to stability studies.

A simple and selective RP-HPLC-UV method with SPE was developed and validated for the quantification of cefotaxime in all-in-one total parenteral nutrition (AIO-TPN) admixtures. Chromatographic separation was achieved on a 5 pm particle size C18 DB column (250 x 4.6 mm id) using the mobile phase ammonium acetate (25 mM, pH 4.0)-50% acetonitrile in methanol (80 + 20, v/v). The flow rate was 0.9 mL/min and the detection wavelength was 254 nm. The analyte was extracted from AIO-TPN admixtures by means of an SPE method. The cefotaxime calibration curve was linear over a concentration range of 100-1400 microg/mL with a correlation coefficient of > or = 0.9994. The intraday accuracy and precision for cefotaxime were < or = -3.15 and < or = 3.08%, respectively, whereas the interday accuracy and precision were < or = -2.48 and < or = 2.25%, respectively. The method was successfully applied to stability studies of cefotaxime in the presence of micronutrients together with low and high concentrations of macronutrients in AIO-TPN admixtures. Cefotaxime was degraded by 13.00 and 26.05% at room temperature (25 +/- 2 degrees C) after 72 h in low and high macronutrient concentration formulations of AIO-TPN admixtures, respectively. The values of cefotaxime degradation rates for low and high macronutrient concentration formulations of AIO-TPN admixtures were -0.164 and -0.353, respectively. These results indicated that there was a higher rate of degradation in the AIO-TPN admixture formulations containing high concentrations of macronutrients.

Assessment of isomalt for colon-specific delivery and its comparison with lactulose.

Lactulose is used as a triggering substance in a unique colon-specific delivery technology called CODESTM. Colonic microflora degrades lactulose and forms short-chain fatty acids to activate the CODESTM system. However, lactulose has been reported to cause a Maillard-type reaction with substances containing primary or secondary amino groups that may produce carcinogenic compounds. Thus, the aim of this study was to look into the possibility to substitute lactulose with isomalt for fabrication of CODESTM. The in vitro degradation of both sugars before incorporating them into the CODESTM system was evaluated with the help of rat caecal microflora. The results showed that isomalt was less efficient with regard to its rate and extent of degradation into short-chain fatty acids by the microflora compared to lactulose. However, the in vitro dissolution study did not show a significant difference in the performance between lactulose and isomalt when they were incorporated separately in CODESTM. A similar result was also obtained in the in vivo study. Based on the above results, isomalt could be used as an alternative to lactulose for colonic delivery system utilizing the principles of CODESTM.

A stability-indicating HPLC-UV method for the quantification of anthocyanin in Roselle (Hibiscus Sabdariffa L.) spray-dried extract, oral powder, and lozenges.

Hibiscus sabdariffa L. (H.S.) plant and its calyces have received much attention from researchers because of their potential medicinal and nutritional values. Calyces are the major source of anthocyanin in this plant. Therefore, a well-developed, efficient, and accurate analytical method is needed to assure proper standardization and control the quality of H.S. plant herbal and nutraceutical products. The objective of this work is to develop a simple, rapid, stability-indicating HPLC-UV method for the quantitative determination of anthocyanin in spray-dried aqueous extract (SDE), oral powder, and compressible lozenges formulations using Delphinidin-3-O-sambubioside (Dp3S) as a marker compound. The chromatographic conditions were optimized using Eclipse plus® C18 column. The mobile phase comprised water acidified with 0.2% formic acid (FA) and acetonitrile (ACN) (90:10, v/v) using a gradient system at a flow rate of 0.8 mL/min. The detection wavelength was 525 nm. The column was maintained at 45 °C, and the injection volume was 15 µL. The developed method was validated according to the international conference of harmonization (ICH) guidelines for linearity, detection and quantitation limits, accuracy, precision, specificity, and robustness. Forced degradation studies under acid, base, oxidation, heat, and U.V light, were performed on the pure compound, extract, and the H.S. developed formulations. Significant degradation of the compound was observed under all tested conditions except U.V. light, where degradation was minimum. There was no interference from impurities, degradation products, or excipients at the retention time of Dp3S 3.2 min indicating the specificity of the method. The developed method was statistically confirmed to be accurate, precise, and reproducible. This simple, rapid, and specific method can be employed efficiently to determine anthocyanin in H.S. plant extract and nutraceutical products.

Formulation and optimization of orally disintegrating tablets of sumatriptan succinate.

The aims of the present research were to mask the intensely bitter taste of sumatriptan succinate and to formulate orally disintegrating tablets (ODTs) of the taste masked drug. Taste masking was performed by coating sumatriptan succinate with Eudragit EPO using spray drying technique. The resultant microspheres were evaluated for thermal analysis, yield, particle size, entrapment efficiency and in vitro taste masking. The tablets were formulated by mixing the taste masked microspheres with different types and concentrations of superdisintegrants and compressed using direct compression method followed by sublimation technique. The prepared tablets were evaluated for weight variation, thickness, hardness, friability, drug content, water content, in vitro disintegration time and in vitro drug release. All the tablet formulations disintegrated in vitro within 37-410 s. The optimized formulation containing 5% Kollidon CL-SF released more than 90% of the drug within 15 min and the release was comparable to that of commercial product (Suminat®). In human volunteers, the optimized formulation was found to have a pleasant taste and mouth feel and disintegrated in the oral cavity within 41 s. The optimized formulation was found to be stable and bioequivalent with Suminat®.

Pulmonary Delivery of Anticancer Drugs via Lipid-Based Nanocarriers for the Treatment of Lung Cancer: An Update.

Lung cancer (LC) is the leading cause of cancer-related deaths, responsible for approximately 18.4% of all cancer mortalities in both sexes combined. The use of systemic therapeutics remains one of the primary treatments for LC. However, the therapeutic efficacy of these agents is limited due to their associated severe adverse effects, systemic toxicity and poor selectivity. In contrast, pulmonary delivery of anticancer drugs can provide many advantages over conventional routes. The inhalation route allows the direct delivery of chemotherapeutic agents to the target LC cells with high local concertation that may enhance the antitumor activity and lead to lower dosing and fewer systemic toxicities. Nevertheless, this route faces by many physiological barriers and technological challenges that may significantly affect the lung deposition, retention, and efficacy of anticancer drugs. The use of lipid-based nanocarriers could potentially overcome these problems owing to their unique characteristics, such as the ability to entrap drugs with various physicochemical properties, and their enhanced permeability and retention (EPR) effect for passive targeting. Besides, they can be functionalized with different targeting moieties for active targeting. This article highlights the physiological, physicochemical, and technological considerations for efficient inhalable anticancer delivery using lipid-based nanocarriers and their cutting-edge role in LC treatment.

Rehydrated lyophilized rifampicin-loaded mPEG-DSPE formulations for nebulization.

Rifampicin-loaded nanoparticles were prepared using two different molecular weights of poly-(ethylene oxide)-block-distearoyl phosphatidyl-ethanolamine (mPEG2000-DSPE and mPEG5000-DSPE) polymers. Particle sizes of all formulations studied were in the range of 162-395 nm. The entrapment efficiency (EE) was not affected by the copolymer's molecular weight, and the highest EE (100%) was obtained with drug to copolymer ratio of 1:5. The differential scanning calorimetry (DSC) thermograms showed Tg of rifampicin-loaded PEG-DSPE nanoparticles that shifted to a lower value, indicating entrapment of rifampicin in polymer matrix. The Fourier transformed infrared spectra revealed no chemical interactions between the drug and both copolymers. The in vitro drug release from the formulations occurred over 3 days and followed first-order release kinetic and Higuchi diffusion model. The nebulization of rehydrated lyophilized rifampicin mPEG-DSPE formulations had mass median aerodynamic diameter of 2.6 microm and fine particle fraction of 42%. The aerodynamic characteristic of the preparations was not influenced by the molecular weight of the copolymers. Therefore, it is suggested that both mPEG-DSPE are promising candidates as rifampicin carrier for pulmonary delivery.

Liquid and Solid Self-Emulsifying Drug Delivery Systems (SEDDs) as Carriers for the Oral Delivery of Azithromycin: Optimization, In Vitro Characterization and Stability Assessment.

Azithromycin (AZM) is a macrolide antibiotic used for the treatment of various bacterial infections. The drug is known to have low oral bioavailability (37%) which may be attributed to its relatively high molecular weight, low solubility, dissolution rate, and incomplete intestinal absorption. To overcome these drawbacks, liquid (L) and solid (S) self-emulsifying drug delivery systems (SEDDs) of AZM were developed and optimized. Eight different pseudo-ternary diagrams were constructed based on the drug solubility and the emulsification studies in various SEDDs excipients at different surfactant to co-surfactant (Smix) ratios. Droplet size (DS) < 150 nm, dispersity (D) ≤ 0.7, and transmittance (T)% > 85 in three diluents of distilled water (DW), 0.1 mM HCl, and simulated intestinal fluids (SIF) were considered as the selection criteria. The final formulations of L-SEDDs (L-F1(H)), and S-SEDDs (S-F1(H)) were able to meet the selection requirements. Both formulations were proven to be cytocompatible and able to open up the cellular epithelial tight junctions (TJ). The drug dissolution studies showed that after 5 min > 90% and 52.22% of the AZM was released from liquid and solid SEDDs formulations in DW, respectively, compared to 11.27% of the pure AZM, suggesting the developed SEDDs may enhance the oral delivery of the drug. The formulations were stable at refrigerator storage conditions.

Preparation, characterization, and in vivo evaluation of insulin-loaded PLA-PEG microspheres for controlled parenteral drug delivery.

AIM: The aim of this study was to prepare insulin-loaded poly(lactic acid)-polyethylene glycol microspheres that could control insulin release at least for 1 week and evaluate their in vivo performance in a streptozotocin-induced diabetic rat model. METHODS: The microspheres were prepared using a water-in-oil-in-water double emulsion solvent evaporation technique. Different formulation variables influencing the yield, particle size, entrapment efficiency, and in vitro release profiles were investigated. The pharmacokinetic study of optimized formulation was performed with single dose in comparison with multiple dose of Humulin 30/70 as a reference product in streptozotocin-induced diabetic rats. RESULTS: The optimized formulation of insulin microspheres was nonporous, smooth-surfaced, and spherical in structure under scanning electron microscope with a mean particle size of 3.07 microm and entrapment efficiency of 42.74% of the theoretical amount incorporated. The in vitro insulin release profiles was characterized by a bimodal behavior with an initial burst release because of the insulin adsorbed on the microsphere surface, followed by slower and continuous release corresponding to the insulin entrapped in polymer matrix. CONCLUSIONS: The optimized formulation and reference were comparable in the extent of absorption. Consequently, these microspheres can be proposed as new controlled parenteral delivery system.

Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation.

Introduction: Insulin is given by injection, because when administered orally, it would be destroyed by enzymes in the digestive system, hence only about 0.1% reaches blood circulation. The purpose of the present study was to use pH sensitive polyelectrolyte methyl methacrylate (MMA)/itaconic acid (IA) nanogels as carriers in an attempt to improve absorption of insulin administered orally. Methods: Insulin (Ins) was incorporated into the MMA/IA nanogels (NGs) using the polyelectrolyte complexation (PEC) method to form Ins/NGs-PEC. Several parameters, including Ins:NGs ratio, pH, incubation time and stirring rate were optimized during preparation of InsNGs-PEC. The prepared formulations were characterized in terms of particle size (PS), polydispersity index (PdI), zeta potential (ZP) and percent entrapment efficiency (% EE). Results: The optimized InF12 nanogels had a PS, PdI, ZP and %EE of 190.43 nm, 0.186, -16.70 mV and 85.20%, respectively. The InF12 nanogels were lyophilized in the presence of different concentrations of trehalose as cryoprotectant. The lyophilized InF12 containing 2%w/v trahalose (InF12-Tre2 nanogels) was chosen as final formulation which had a PS, PdI, ZP and %EE of 430.50 nm, 0.588, -16.50 mv and 82.10, respectively. The in vitro release of insulin from InF12-Tre2 nanogels in the SGF and SIF were 28.71% and 96.53%, respectively. The stability study conducted at 5±3°C for 3 months showed that lnF12-Tre2 nanogels were stable. The SDS-PAGE assay indicated that the primary structure of insulin in the lnF12-Tre2 nanogels was intact. The in-vivo study in the diabetic rats following oral administration of InF12-Tre2 nanogels at a dose of 100 IU/kg body weight reduced blood glucose level significantly to 51.10% after 6 hours compared to the control groups. Conclusions: The pH sensitive MMA/IA nanogels are potential carriers for oral delivery of insulin as they enhanced the absorption of the drug.

Microencapsulation Curcuminoids for Effective Delivery in Pharmaceutical Application.

Curcuminoids have been long proven to possess antioxidant, anti-inflammatory and antibacterial properties which are crucial in their role as a pharmacological active agent. However, its poor solubility, high oxidative degradation, light sensitivity and poor bioavailability have been huge hurdles that need to be overcome for it to be administered as an oral or even a topical medication. In this present study, a complex coacervation microencapsulation approach was used to encapsulate the curcuminoids using both gelatin B and chitosan (at the optimum ratio of 30:1% w/w) for a more efficient drug delivery system. Curcuminoids microcapsules (CPM) were developed to be spherical in shape, discrete and free flowing with a reduced color staining effect. The thick wall of the CPM contributes directly to its integrity and stability. Cross-linking increases the density of polymers' wall network, hence, further increasing the decomposition temperature of curcuminoids microcapsules. Microencapsulation demonstrated an increment in curcuminoids solubility, while chemical cross-linking allowed for sustained release of the drug from the microcapsules by lowering the swelling rate of the available polymer networks. Thus, the microcapsules complied with the zero order release kinetics with super case-II transport mechanism. On the basis of all that was discussed above, it can be safely concluded that CPM should be incorporated in delivery system of curcuminoid, especially in its topical delivery for controlled drug release purposes, for not only a more efficient drug delivery system design but also a more efficacious optimization of the pharmacological benefits of curcuminoids.

Freeze-Dried Lopinavir-Loaded Nanostructured Lipid Carriers for Enhanced Cellular Uptake and Bioavailability: Statistical Optimization, in Vitro and in Vivo Evaluations.

Nanostructured lipid carriers (NLCs) loaded with lopinavir (LPV) were prepared by the high-shear homogenization method. The LPV-NLCs formulations were freeze-dried using trehalose as a cryoprotectant. In vitro release studies in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8) showed a burst release. The optimized freeze-dried formulation (LPV-NLC-7-Tres) had a particle size (PS), polydispersity index (PdI), zeta potential (ZP) and % entrapment efficiency (%EE) of 286.8 ± 1.3 nm, 0.413 ± 0.017, -48.6 ± 0.89 mV and 88.31 ± 2.04%, respectively. The optimized formulation observed by transmission and scanning electron microscopes showed a spherical shape. Differential scanning calorimetry study revealed the absence of chemical interaction between the drug and lipids. In vitro cellular uptake study using Caco-2 cell line showed a higher LPV uptake from LPV-NLC-7-Tres formulation compared to the free LPV-suspension. The 6-month stability study showed a minimum rise of ~40 nm in PS, while no significant changes in PdI, ZP and drug content of the LPV-NLC-7-Tres formulation stored at 5 °C ± 3 °C. The bioavailability of LPV following oral administration of LPV-NLC-7-Tres in male Wistar rats was found 6.98-fold higher than the LPV-suspension. In conclusion, the nanostructure lipid carriers are potential carriers for improving the oral bioavailability of lopinavir.

Wound Healing Property of Curcuminoids as a Microcapsule-Incorporated Cream.

Curcuminoids have been used for the management of burns and wound healing in traditional Chinese medicine practices but the wide application of curcuminoids as a healing agent for wounds has always been a known problem due to their poor solubility, bioavailability, colour staining properties, as well as due to their intense photosensitivity and the need for further formulation approaches to maximise their various properties in order for them to considerably contribute towards the wound healing process. In the present study, a complex coacervation microencapsulation was used to encapsulate curcuminoids using gelatin B and chitosan. This study also focused on studying and confirming the potential of curcuminoids in a microencapsulated form as a wound healing agent. The potential of curcuminoids for wound management was evaluated using an in vitro human keratinocyte cell (HaCaT) model and the in vivo heater-inflicted burn wound model, providing evidence that the antioxidant activities of both forms of curcuminoids, encapsulated or not, are higher than those of butylated hydroxyanisole and butylated hydroxytoluene in trolox equivalent antioxidant capacity (TEAC) and (2,2-diphenyl-1-picryl-hydrazyl-hydrate) (DPPH) studies. However, curcuminoids did not have much impact towards cell migration and proliferation in comparison with the negative control in the in vitro HaCaT study. The micoencapsulation formulation was shown to significantly influence wound healing in terms of increasing the wound contraction rate, hydroxyproline synthesis, and greater epithelialisation, which in turn provides strong justification for the incorporation of the microencapsulated formulation of curcuminoids as a topical treatment for burns and wound healing management as it has the potential to act as a crucial wound healing agent in healthcare settings.

Lyophilized Hybrid Nanostructured Lipid Carriers to Enhance the Cellular Uptake of Verapamil: Statistical Optimization and In Vitro Evaluation.

Verapamil is a calcium channel blocker and highly effective in the treatment of hypertension, angina pectoris, and other diseases. However, the drug has a low bioavailability of 20 to 35% due to the first pass effect. The main objective of this study was to develop hybrid verapamil-dextran nanostructured lipid carriers (HVD-NLCs) in an attempt to increase verapamil cellular uptake. The formulations were successfully prepared by a high-shear homogenization method and statistically optimized using 24 full factorial design. The HVD-NLCs formulations were freeze-dried using trehalose as a cryoprotectant. The results showed that the optimized formula (VER-9) possessed a particle size (PS), polydispersity index (PDI), and the percentage of entrapment efficiency (%EE) of 192.29 ± 2.98, 0.553 ± 0.075, and 93.26 ± 2.66%, respectively. The incorporation of dextran sulfate in the formulation had prolonged the release of verapamil (~ 85% in 48 h) in the simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8). The differential scanning calorimetry analysis showed no chemical interaction between verapamil and the excipients in the formulation. While wide-angle X-ray scattering studies demonstrated the drug in the amorphous form after the incorporation in the NLCs. The transmission electron microscopy and scanning electron microscopy images revealed that the nanoparticles had spherical shape. The cellular uptake study using Caco-2 cell line showed a higher verapamil uptake from HVD-NLCs as compared to verapamil solution and verapamil-dextran complex. The optimized formulation (VER-9) stored in the refrigerated condition (5 °C ± 3 °C) was stable for 6 months. In conclusion, the HVD-NLCs were potential carriers for verapamil as they significantly enhanced the cellular uptake of the drug.

Transethosomal gels as carriers for the transdermal delivery of colchicine: statistical optimization, characterization, and ex vivo evaluation.

INTRODUCTION: Colchicine is used for the treatment of gout, pseudo-gout, familial Mediterranean fever, and many other illnesses. Its oral administration is associated with poor bioavailability and severe gastrointestinal side effects. The drug is also known to have a low therapeutic index. Thus to overcome these drawbacks, the transdermal delivery of colchicine was investigated using transethosomal gels as potential carriers. METHODS: Colchicine-loaded transethosomes (TEs) were prepared by the cold method and statistically optimized using three sets of 24 factorial design experiments. The optimized formulations were incorporated into Carbopol 940® gel base. The prepared colchicine-loaded transethosomal gels were further characterized for vesicular size, dispersity, zeta potential, drug content, pH, viscosity, yield, rheological behavior, and ex vivo skin permeation through Sprague Dawley rats' back skin. RESULTS: The results showed that the colchicine-loaded TEs had aspherical irregular shape, nanometric size range, and high entrapment efficiency. All the formulated gels exhibited non-Newtonian plastic flow without thixotropy. Colchicine-loaded transethosomal gels were able to significantly enhance the skin permeation parameters of the drug in comparison to the non-ethosomal gel. CONCLUSION: These findings suggested that the transethosomal gels are promising carriers for the transdermal delivery of colchicine, providing an alternative route for drug administration.

Characterization of polymeric micelles for pulmonary delivery of beclomethasone dipropionate.

The potential of using poly-(ethylene oxide)-block-distearoyl phosphatidyl-ethanolamine (mPEG-DSPE) polymer to prepare BDP-loaded micelles with high entrapment efficiency and mass median aerodynamic diameter of less than 5 microm demonstrating sustained release properties was evaluated. The result showed that lyophilized BDP-loaded polymeric micelles with entrapment efficiency of more than 96% could be achieved. Entrapment efficiency was affected by both the drug to polymer molar ratio and the amount of drug used. Investigation using FTIR and DSC confirmed that there was no chemical or physical interaction and the drug was molecularly dispersed within the micelles. TEM images showed that the drug-loaded polymeric micelles were spherical in shape with multivesicular morphology. Further analysis by photon correlation spectroscopy indicated that the particle size of the BDP-loaded micelles was about 22 nm in size. In vitro drug release showed a promising sustained release profile over six days following the Higuchi model. The mass median aerodynamic diameter and fine particle fraction were suitable for pulmonary delivery. Moreover, the small amount of deposited drug in the induction port (throat deposition) suggested possible reduction in incidence of oropharyngeal candidiasis, a side effect normally associated with inhaled corticosteroids therapy. The high encapsulation efficiency, comparable inhalation properties, sustained release behavior together with biocompatibility nature of the polymer support the potential of BDP-loaded polymeric micelles as a versatile delivery system to be used in the treatment of asthma and chronic obstructive pulmonary disease.

Ethosomal nanocarriers: the impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials.

Ethosomal systems are novel lipid vesicular carriers containing a relatively high percentage of ethanol. These nanocarriers are especially designed for the efficient delivery of therapeutic agents with different physicochemical properties into deep skin layers and across the skin. Ethosomes have undergone extensive research since they were invented in 1996; new compounds were added to their initial formula, which led to the production of new types of ethosomal systems. Different preparation techniques are used in the preparation of these novel carriers. For ease of application and stability, ethosomal dispersions are incorporated into gels, patches, and creams. Highly diverse in vivo models are used to evaluate their efficacy in dermal/transdermal delivery, in addition to clinical trials. This article provides a detailed review of the ethosomal systems and categorizes them on the basis of their constituents to classical ethosomes, binary ethosomes, and transethosomes. The differences among these systems are discussed from several perspectives, including the formulation, size, ζ-potential (zeta potential), entrapment efficiency, skin-permeation properties, and stability. This paper gives a detailed review on the effects of ethosomal system constituents, preparation methods, and their significant roles in determining the final properties of these nanocarriers. Furthermore, the novel pharmaceutical dosage forms of ethosomal gels, patches, and creams are highlighted. The article also provides detailed information regarding the in vivo studies and clinical trials conducted for the evaluation of these vesicular systems.

Solid Lipid Nanoparticles of Atovaquone Based on 2(4) Full-Factorial Design.

Solid lipid nanoparticles of atovaquone (ATQ-SLN) were prepared by high shear homogenization method using tripalmitin, trilaurin, and Compritol 888 ATO as the lipid matrices and Phospholipon 90H, Tween 80, and poloxamer 188 as the surfactants. Optimization of the formulations was conducted using 6 sets of 2(4) full-factorial design based on four independent variables that were the number of homogenizing cycles, concentration of the lipid, concentration of the co-surfactant, and concentration of the main surfactant. The dependent variables were particle size and polydispersity index (PdI). The homogenizing cycles showed a negative influence on the dependent variables which reduced both the particle size and the PdI value. Moreover, a combination of certain percentages of the main surfactant and co-surfactant also showed a negative influence that reduced both the particle size and PdI value. Selected formulations from each design were further characterized for the entrapment efficiency and yield. The optimised formulation of ATQ-SLN consisted of trilaurin, Phospholipon 90H and Tween 80 with a particle size of 89.4 ± 0.2 nm and entrapment efficiency of 83.0 ± 1.7%. The in-vitro release evaluation of the formulation showed a complete and immediate release of ATQ from the SLN that could be a solution to improve the poor aqueous solubility and hence poor bioavailability of the drug.

Advanced drug delivery to the lymphatic system: lipid-based nanoformulations.

The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipid-based nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects uptake of drug into the lymphatic system. Two lipid-based nanoformulations, ie, solid lipid nanoparticles and nanostructured lipid carriers, have been administered via multiple routes (subcutaneous, pulmonary, and intestinal) for targeting of the lymphatic system. This paper provides a detailed review of novel lipid-based nanoformulations and their lymphatic delivery via different routes, as well as the in vivo and in vitro models used to study drug transport in the lymphatic system. Physicochemical properties that influence lymphatic delivery as well as the advantages of lipid-based nanoformulations for lymphatic delivery are also discussed.

Solubilization of beclomethasone dipropionate in sterically stabilized phospholipid nanomicelles (SSMs): physicochemical and in vitro evaluations.

BACKGROUND: The local treatment of lung disorders such as asthma and chronic obstructive pulmonary disease via pulmonary drug delivery offers many advantages over oral or intravenous routes of administration. This is because direct deposition of a drug at the diseased site increases local drug concentrations, which improves the pulmonary receptor occupancy and reduces the overall dose required, therefore reducing the side effects that result from high drug doses. From a clinical point of view, although jet nebulizers have been used for aerosol delivery of water-soluble compounds and micronized suspensions, their use with hydrophobic drugs has been inadequate. AIM: To evaluate the feasibility of sterically stabilized phospholipid nanomicelles (SSMs) loaded with beclomethasone dipropionate (BDP) as a carrier for pulmonary delivery. METHODS: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 5000) polymeric micelles containing BDP (BDP-SSMs) were prepared by the coprecipitation and reconstitution method, and the physicochemical and in vitro characteristics of BDP-SSMs were investigated. RESULTS: BDP-SSMs were successfully prepared with a content uniformity and reproducibility suitable for pulmonary administration. The maximum solubility of BDP in SSMs was approximately 1300 times its actual solubility. The particle size and zeta potential of BDP-SSMs were 19.89 ± 0.67 nm and -28.03 ± 2.05 mV, respectively. The SSMs system slowed down the release of BDP and all of the aerodynamic values of the aerosolized rehydrated BDP-SSMs were not only acceptable but indicated a significant level of deposition in the lungs. CONCLUSION: The SSM system might be an effective way of improving the therapeutic index of nebulized, poorly soluble corticosteroids.