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One of the widely efficient and noteworthy nanocarriers that could draw a great attention toward pharmaceutical fields is nanoemulsions (NEs). NEs are thermodynamically stable colloidal dispersions composed of two immiscible liquids, oil and water that mixed together using emulsifying agent (surfactant and co-surfactant). It regarded as pharmaceutical dosage form having droplet size within a nanometer range, hence it has extensively considered as carrier for delivering active agents. Such carrier is fabricated in order to overcome some obstacles associated with conventional drug delivery systems especially low bioavailability. The objective of this review is to present an overview about NE and its latest applications in diverse areas such as drug delivery, cosmeceutical and nutraceutical. Clarifications about different mechanisms of NEs development that are frequently used were provided. Correspondingly, popular characterization techniques for NEs such as determination of particle size, polydispersity index (PDI), zeta potential and viscosity were reviewed. Eventually, summary of physical and chemical instability in addition to the regulatory aspects of NE were provided.

The application of nanotechnology to drug delivery systems for cancer therapy has progressively received great attention. The most heavily investigated approach is the development of nanoparticles (NPs) utilizing biodegradable and biocompatible polymers such as poly (lactic-co-glycolic acid) (PLGA). These NPs could be further improved by surface modification utilizing a hydrophilic biodegradable polymer such as polyethylene glycol (PEG) to achieve passive targeting. Modified NPs can deliver drugs such as brucine (BRU), which has shown its potential in cancer therapy. The objective of the current investigation was to develop and evaluate the passive targeting of long-circulating PLGA NPs loaded with BRU. NPs were characterized in terms of drug-excipient compatibility studies, including FTIR and DSC; physicochemical evaluations including particle size, zeta potential, morphological evaluation, entrapment efficiency and percentage yield; total serum protein adsorbed onto NP surfaces; and in vitro release of the loaded drug. Factorial design was employed to attain optimal PLGA-loaded NPs. Finally, the in vivo anti-tumor activity of BRU-loaded PLGA NPs was evaluated in tumor-bearing mice. The NPs obtained had smooth surfaces with particle sizes ranged from 94 ± 3.05 to 253 ± 8.7 nm with slightly positive surface charge ranged from 1.09 ± 0.15 to 3.71 ± 0.44 mV. Entrapment of BRU ranged between 37.5 ± 1.8% and 77 ± 1.3% with yields not less than 70.8%. Total protein adsorbed was less than 25.5 µg total protein/1 mg NP. In vitro drug release was less than 99.1% at 168 h. Finally, significant reductions in tumor growth rate and mortality rate were observed for PEG PLGA NP formulations compared to both BRU solution and naked NPs.

The aim of the study was to design a self-emulsifying drug delivery system (SEDDS) of the anti-hypertensive Carvedilol in liquid and liquisolid forms as a way to enhance its dissolution profile and anti-hypertensive effect.Solubility studies of Carvedilol in various oils, surfactants and co-surfactants were conducted, followed by the construction of pseudo-ternary phase diagrams and other in vitro assessments. The selected SEDDS formulation (S1) was adsorbed onto solid powder excipients and compressed into tablets. The resulting liquisolid tablets were evaluated under British Pharmacopoeia (B.P.) specifications. Pre- and post-compression studies were performed to determine the flow properties and evaluate the liquisolid systems, followed by in vivo studies in hypertensive rats.Attempts of self-emulsification, droplet size, and thermodynamic stability studies showed acceptable results for the S1 formulation containing Capryol 90, Tween 20, and Transcutol HP (10:53.3:26.2%), respectively. Pre-compression studies showed adequate flowability and compatibility of liquid and solid excipients with Carvedilol. The selected liquisolid tablet (LS7) demonstrated the best disintegration and water absorption ratio in addition to satisfactory friability and hardness. A significantly (p .05) fast dissolution rate was observed for both SEDDS and liquisolid formulations when compared to pure drug and marketed CarvepressSelf-emulsifying liquisolid tablets expressed rapid onset of action with enhanced anti-hypertensive effect of Carvedilol.

Doxazosin Mesylate (DOX) is an antihypertensive drug which possesses poor water solubility and hence low bioavailability. The study objective is to prepare DOX fast disintegrating tablets as a new dosage form for geriatric patients. First, 23 full factorial design using Polyvinyl pyrrolidone k 30, Poloxamer-407 and Sodium Lauryl Sulphate at low and high ratios were used for preparation of DOX nanosuspension as a trial to improve its dissolution properties. Nanosuspension formulations were characterized using Transmission electron microscopy, Differential scanning calorimetry and Fourier transform infrared spectroscopy. Then, the optimized formula was incorporated in fast disintegrating tablets using different superdisintegrants. The tablets were evaluated for hardness, thickness, friability percentage, diameter, weight variation, Wetting time, disintegration time and percentage dissolution after 10 min. A significant reduction (rapidly and efficiently) in mean arterial pressure of hypertensive rats was observed for DOX nanosuspension fast disintegrating tablet using Ac-Di-Sol as a superdisintegrant with 100% dissolution after 10 min.

The present study aims to emphasize the enhanced efficacy of long acting in-situ gel forming implants (ISGFI) based on poly (lactic-co-glycolic acid) (PLGA) matrix to deliver anti-psychotic risperidone over extended time periods with reduced administration frequency. Schizophrenic patients show considerable difficulties in adherence and compliance to oral medications associated with negative outcomes including symptoms exacerbation and psychotic relapse. The studied optimized ISGFI formulation, comprised of 2.85:1 ratio of DMSO solvent:PLGA (type 75:25), was subjected to various characterization studies including morphological real-time changes, scanning electron microscopy and in-vitro drug release study. Pharmacokinetics and behavioral evaluations of anti-psychotic action of ISGFI systems were pursued on healthy and schizophrenia-induced rats respectively then compared to results of marketed microspheres. Morphological observations showed the immediate formation of whitish smooth ISGFI system owing to the rapid PLGA solidification after rapid DMSO dissipation into the external medium. Scanning electron microscopy confirmed the slow gradual biodegradation of the formed ISGFI. The optimized formulation assured its effectiveness to produce satisfactory initial burst and cumulative risperidone release and obviate costs of additional tablets needed during the commercial product use. Pharmacokinetic study manifested the effective performance of ISGFI to extend risperidone release for longer period (72 days) in comparison to the marketed formulations (48 days). Besides, optimized ISGFI were more effective in improving ketamine-induced schizophrenia-like symptoms in experimental rats, particularly in the first week of study period. Meanwhile, in-vitro, pharmacokinetic and pharmacodynamic evaluations had advocated the potential advantages of ISGFI systems for treating schizophrenia with improved adherence and compliance of patients.

Cancer represents one of the most life threatening disease worldwide. Poly ethylene glycol nanoemulsion (PEG-NE), a new drug delivery system (DDS) is widely utilized for encapsulating water insoluble drugs and delivering it into cancerous tissue following its intravenous injection. Brucine (BRU) is an effective anti-carcinogenic agent toward different cancer cell lines; however, its low solubility represents a great obstacle in its formulation. The objective of this investigation was to develop and evaluate BRU-PEG-NE. Physicochemical evaluation including, viscosity, particle size and entrapment efficiency investigations were performed. Quantitative and qualitative estimation of total serum protein adsorbed onto the surface of BRU-NE were performed. in vitro release studies of BRU-NE with and without serum incubation were assayed. Formulations were tested for their cytotoxic activity using MTT assay. Finally, in-vivo anticancer effect was evaluated in tumor-inoculated mice. Homogenous NEs were obtained with particle size less than 140 nm and viscosity less than 3.3 cP for BRU-PEG-NE. Total serum protein adsorbed was less than 17.33 ± 0.76 μg/μmol total lipid for BRU-PEG-NE. in vitro drug release was less than 65 % over 24 h for PEG-NE. As well, PEG-NEs could achieve significant inhibition for the viability of cancer cells. Finally, significant reduction in tumor growth rate and mortality rate for BRU PEG-NE formulations were obtained. The obtained results suggested that BRU PEG NE could be considered as a potential mean for cancer therapy.

We recently developed a PEG-coated liposome encapsulating the anti-folate drug pemetrexed (PMX). Such liposomal formulations have shown potent cytotoxic effects against malignant pleural mesothelioma (MPM) cells in vitro. In the present study, we investigated the pharmacokinetics, bio-distribution and in vivo anti-tumor efficacy of two liposomal PMX formulations with different drug release rates in a murine mesothelioma-xenograft model. Liposomes with different PMX release rates were prepared via manipulating liposomal membrane fluidity through incorporating either a solid-phase (HSPC) or a fluid-phase (POPC) phospholipid. Both liposomal PMX formulations showed prolonged plasma pharmacokinetics and were accumulated to a similar extent in tumors and other tissues, presumably, due to surface modification with polyethylene glycol (PEG). In a murine mesothelioma-xenograft model, interestingly, PMX encapsulated in a fast-release POPC liposome produced superior tumor growth suppression compared with either free PMX or PMX encapsulated in a slow-release HSPC liposome. Such in vivo anti-tumor efficacy was accomplished mainly by a potent induction of apoptosis within tumor tissue by the released PMX from POPC liposomes. Our results clearly emphasize the therapeutic efficacy of liposomal PMX over free PMX in conquering aggressive solid tumors such as malignant mesothelioma. A guarantee of the targeted delivery of PMX to tumor cells helps overcome some of the major shortcomings encountered with the use of free PMX.

The current study aims to develop in-situ forming implants (ISFI) of anti-psychotic risperidone to customize schizophrenia therapy. Non-adherence to treatment is the most prevalent unsuccessful clinical outcome in schizophrenic patients. Poly(lactic-co-glycolic acid) (PLGA) was utilized to prepare ISFI using various solvents having different drug solubilization capacity. 33 Box-Behnken Design (BBD) was used to study the effects of independent variables; lactide concentration (A), solvent type (B) and solvent/polymer ratio (S/P) (C) on burst release after 6h (Y1), cumulative release after 40 days (Y2) and injectability time (Y3). Statistical analysis was followed by optimization process to minimize burst release and injectability time with targeted cumulative release to 50% at 40 days. BBD results represented the critical impacts of increasing lactide and PLGA concentrations on reducing drug burst and percent release. Rapid ISFI solidification using DMSO supported the high dispersed drug encapsulation and sustained release. Triacetin demonstrated a lag time between formulation injection and solidification that negatively affected the studied responses. The optimized formulation manifested burst (8.1%), cumulative release (51.08%) and 18 s for injection by mixing PLGA (75:25) and DMSO (S/P = 2.851). Compared with injectable commercial microspheres, ISFI emphasized their potential to enhance compliance and eliminate costs issues of additional oral therapy.

For patient convenience, sustained release Adefovir Poly-d,l-lactic-co-glycolic acid (PLGA) microspheres were formulated to relieve the daily use of the drug which is a problem for patients treated from chronic hepatitis-B. PLGA microspheres were prepared and characterized by entrapment efficiency, particle size distribution and scanning electron microscopy (SEM). In-vitro release and in-vivo studies were carried out. Factors such as drug: polymer ratio, polymer viscosity and polymer lactide content were found to be important variables for the preparation of PLGA Adefovir microspheres. Fourier transform infrared (FTIR) analysis and differential scanning calorimetry (DSC) were performed to determine any drug-polymer interactions. One way analysis of variance (ANOVA) was employed to analyze the pharmacokinetic parameters after intramuscular injection of the pure drug and the selected PLGA microspheres into rats. FTIR and DSC revealed a significant interaction between the drug and the polymer. Reports of SEM before and after 1 and 24 h release showed that the microspheres had nonporous smooth surface even after 24 h release. The entrapment efficiency ranged between 55.83 and 86.95% and in-vitro release studies were continued for 16, 31 and 90 days. The pharmacokinetic parameters and statistical analysis showed a significant increase in the Tmax, AUC0–t and MRT, and a significant decrease in the Cmax of the tested formulation (p