Development of Self-Microemulsifying Drug Delivery System to Improve Nisoldipine Bioavailability: Cell Line and In Vivo Evaluations : Development of Self-Microemulsifying Drug Delivery System.

The authors attempted to fabricate a novel lipid-based formulation of a lipophilic drug, nisoldipine (NISO). As NISO belongs to BCS class 2 drug, it suffers from low bioavailability (5%). Hence, the research was intended to ameliorate oral bioavailability of NISO via intestinal lymphatic transport. The NISO loaded self microemulsifying drug delivery system (SMEDDS) (NISO SMEDDS) was prepared using Peceol, Cremophor EL, and Transcutol HP. The Cremophor EL and Transcutol HP at 1:1 ratio showed maximum microemulsifying area, and average globule size was 16.78 ± 0.97 nm with PDI 0.121 ± 0.024. Cellular uptake studies (confocal microscopy and flow cytometry) using Caco-2 cells depicted higher fluorescence with coumarin-6 loaded SMEDDS as that of coumarin-6 solution which indicated deeper penetration. Mean fluorescence intensity (MFI) of coumarin-6 loaded SMEDDS was significantly improved (9.92-fold) in contrast to coumarin-6 solution. The NISO SMEDDS showed enhanced permeability (5.02 times) across Caco-2 cells compared to NISO suspension. The bioavailability improvement with NISO SMEEDS was 2.14 times relative to suspension, and lymphatic uptake was involved in oral absorption of NISO SMEDDS.

Enhanced bioavailability and antihypertensive activity of nisoldipine loaded nanoemulsion: optimization, cytotoxicity and uptake across Caco-2 cell line, pharmacokinetic and pharmacodynamic studies.

Objective: The present study explored the antihypertensive activity of nisoldipine in oil in water nanoemulsion to improve its oral bioavailability via intestinal lymphatic uptake.Methods: Nanoemulsion was prepared by ultrasonication technique using Peceol, Cremophor EL and Transcutol HP as oil, surfactant and cosurfactant respectively. Optimization was done employing 32 full factorial design. The developed formulation was assessed for in vitro,cell line, ex vivo and in vivo studies.Results: The experimental results indicated homogeneity of the nanoemulsion with globule size of 62.35 ± 2.55 nm and PDI value of 0.108 ± 0.01 with negative zeta potential (-26.2 ± 3.6 mV). Transmission electron microscopy showed spherical oil globules morphology. The in vitro diffusion study showed significant increase in drug release from NE formulations (98.51 ± 2.64%) as compared to plain drug dispersion (29.73 ± 2.15%) in 0.1 N HCl + 0.5% SLS medium. Moreover, higher quantitative and qualitative uptake of nanoemulsion via Caco-2 cells showed superior intestinal absorption and improved therapeutic activity of nisoldipine when compared to drug dispersion. Pharmacokinetic and pharmacodynamic study confirmed significantly (p ˂ 0.05) greater bioavailability and antihypertensive activity of nisoldipine nanoemulsion when compared to its dispersion. These results are visualized in abstract figure.Conclusion: Thus, prepared nanoemulsion showed potential as oral delivery system for nisoldipine with superior oral bioavailability and therapeutic efficacy over drug dispersion.

Fabrication of solid lipid nanoparticles of lurasidone HCl for oral delivery: optimization, in vitro characterization, cell line studies and in vivo efficacy in schizophrenia.

Objective: The aim of the present investigation was to investigate the efficacy of solid lipid nanoparticles (SLNs) to enhance the absorption and bioavailability of lurasidone hydrochloride (LH) following oral administration. Methods: The LH loaded SLNs (LH-SLNs) were prepared by high pressure homogenization (HPH) method, optimized using box Behnken design and evaluated for particle size (PS), entrapment efficiency (EE), morphology, FTIR, DSC, XRD, in vitro release, ex vivo permeation, transport studies across Caco-2 cell line and in vivo pharmacokinetic and pharmacodynamic studies. Results: The LH-SLNs had PS of 139.8 ± 5.5 nm, EE of 79.10 ± 2.50% and zeta potential of -30.8 ± 3.5 mV. TEM images showed that LH-SLNs had a uniform size distribution and spherical shape. The in vitro release from LH-SLNs followed the Higuchi model. The ex vivo permeability study demonstrated enhanced drug permeation from LH-SLNs (>90%) through rat intestine as compared to LH-suspension. The SLNs were found to be taken up by energy dependent, endocytic mechanism which was mediated by clathrin/caveolae-mediated endocytosis across Caco-2 cell line. The pharmacokinetic results showed that oral bioavailability of LH was improved over 5.16-fold after incorporation into SLNs as compared to LH-suspension. The pharmacodynamic study proved the antipsychotic potential of LH-SLNs in the treatment of schizophrenia. Conclusion: It was concluded that oral administration of LH-SLNs in rats improved the bioavailability of LH via lymphatic uptake along with improved therapeutic effect in MK-801 induced schizophrenia model in rats.

Novel Drug Delivery Approach via Self-Microemulsifying Drug Delivery System for Enhancing Oral Bioavailability of Asenapine Maleate: Optimization, Characterization, Cell Uptake, and In Vivo Pharmacokinetic Studies.

Asenapine maleate (AM)-loaded self-microemulsifying drug delivery system (AM-SMEDDS) was prepared to increase its oral bioavailability. AM-SMEDDS was developed using Capryol 90, Cremophor EL, and Transcutol HP as oil, surfactant, and cosurfactant, respectively, by spontaneous emulsification method. Pseudoternary diagram showed maximum region at 3:1 ratio of Cremophor EL/Transcutol HP. The AM-SMEDDS showed globule size and zeta potential of 21.1 ± 1.2 nm and - 19.3 ± 1.8 mV, respectively. Globules were found to be of spherical shape and uniformly distributed by transmission electron microscopy. In vitro drug release study showed 99.2 ± 3.3% of drug release at the end of 8 h in phosphate buffer pH 6.8. Ex vivo drug release study showed only 15% of drug diffusion through stomach and ~ 85% drug was diffused through intestinal membrane. Confocal and flow cytometry study showed that cellular uptake of coumarin-6 loaded SMEDDS was significantly enhanced by Caco-2 cells as that of coumarin-6 solution. The relative bioavailability of AM-SMEDDS was found to be 23.53 times greater than AM suspension. Intestinal lymphatic transport study using Cycloheximide (CHX) showed that the AUCtotal of AM-SMEDDS reduced about 35.67% compared with that without the treatment of CHX indicating involvement of lymphatic system in intestinal absorption of AM-loaded SMEDDS. These findings demonstrated the potential of SMEDDS for oral bioavailability improvement of AM via lymphatic uptake. Graphical Abstract.

Comparative Study for Optimization of Pharmaceutical Self-Emulsifying Pre-concentrate by Design of Experiment and Artificial Neural Network.

The present investigation aimed to optimize the critical parameters affecting the globule size of self-emulsifying drug delivery system. Based on preliminary screening, three critical parameters, viz., amount of oil, surfactant, and co-surfactant were found to affect the globule size. I-optimal mixture design and Artificial Neural Network (ANN) were used to optimize the formulation with respect to minimum globule size. Comparative study was carried out to identify which optimization technique gave better predictability for the selected output parameter. R-value and MSE values were taken into consideration for comparison of both techniques. Using Response Surface Methodology-based I-optimal mixture design approach, the R2 value was found to be 0.9867, whereas with ANN technique, it was found to be 0.99548. The predicted size for the optimized batch by I-optimal design was 122.377 nm, whereas by ANN, it was 119.6783 nm against the actual obtained size of 118.2 ± 2.3 nm. This analysis indicated superior predictability of output for given input variables by ANN as compared to model-dependent DoE I-optimal design approach.

Development of Novel Octanoyl Chitosan Nanoparticles for Improved Rifampicin Pulmonary Delivery: Optimization by Factorial Design.

A novel hydrophobic chitosan derivative, octanoyl chitosan (OC) with improved organic solubility was synthesized, characterized, and employed for the preparation of rifampicin (Rif) encapsulated nanoparticle formulations for pulmonary delivery. OC was characterized to confirm acyl group substitution and cytotoxicity in A549 epithelial lung cells. OC nanoparticles were produced by the double emulsion solvent evaporation technique without cross-linking and characterized for particle size distribution, morphology, crystallinity, thermal stability, aerosol delivery, and drug release rate. OC was successfully synthesized with substitution degree of 44.05 ± 1.75%, and solubility in a range of organic solvents. Preliminary cytotoxicity studies of OC showed no effect on cell viability over a period of 24 h on A549 cell lines. OC nanoparticles were optimized using a 32 full factorial design. An optimized batch of OC nanoparticles, smooth and spherical in morphology, had mean hydrodynamic diameter of 253 ± 19.06 nm (PDI 0.323 ± 0.059) and entrapment efficiency of 64.86 ± 7.73% for rifampicin. Pulmonary deposition studies in a two-stage impinger following aerosolization of nanoparticles from a jet nebulizer gave a fine particle fraction of 43.27 ± 4.24%. In vitro release studies indicated sustained release (73.14 ± 3.17%) of rifampicin from OC nanoparticles over 72 h, with particles demonstrating physical stability over 2 months. In summary, the results confirmed the suitability of the developed systems for pulmonary delivery of drugs with excellent aerosolization properties and sustained-release characteristics.

Cefdinir nanosuspension for improved oral bioavailability by media milling technique: formulation, characterization and in vitro-in vivo evaluations.

Cefdinir (Cef) is an orally active Biopharmaceutics Classification System (BCS) class IV drug with incomplete absorption and low bioavailability (16-21%). The aim of this investigation was to develop nanosuspensions (NS) of Cef to improve its oral bioavailability. Cef NS were prepared by the media milling technique using zirconium oxide beads as the milling media. Cef NS were characterized by particle size, Scanning Electron Microscopy, Differential Scanning Calorimetry, X-Ray Diffraction pattern and evaluated for saturation solubility, in vitro release studies, ex vivo permeability studies and in vivo bioavailability studies. The particle size and zeta potential were found to be 224.2 ± 2.7 nm and -15.7 ± 1.9 mV, respectively. Saturation solubility of NS was found to be 1985.3 ± 10.2 µg/ml which was 5.64 times higher than pure drug (352.2 ± 6.5 µg/ml). The DSC thermograms and XRD patterns indicated that there was no interaction between drug and excipients and that the crystallinity of Cef remained unchanged after media milling process. Results of in vitro release studies and ex vivo permeation studies showed improved drug release of 88.2 1 ± 2.90 and 83.11 ± 2.14%, respectively, from NS after 24 h as compared to drug release of 54.09 ± 2.54 and 48.2 1 ± 1.27%, respectively, from the marketed suspension (Adcef). In vivo studies in rats demonstrated a 3-fold increase in oral bioavailability from the NS in comparison to marketed suspension. The results of this investigation conclusively show that the developed nanosuspension of Cef exhibited improved solubility, dissolution and permeation which led to a significant enhancement in its oral bioavailability.

Design and evaluation of mucoadhesive microemulsion for neuroprotective effect of ibuprofen following intranasal route in the MPTP mice model.

BACKGROUND: The present study is to investigate the neuroprotective effect of ibuprofen by intranasal administration of mucoadhesive microemulsion (MMEI) against inflammation-mediated by dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). METHODS: Ibuprofen-loaded polycarbophil-based MMEI was developed by using response surface methodology (RSM). Ibuprofen with dose of 2.86 mg/kg/day was administered intranasally to male C57BL/6 mice for two consecutive weeks which were pre-treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals. Immunohistochemistry was performed. RESULTS: Optimal MMEI was stable and non-ciliotoxic with 66.29 ± 4.15 nm as average globule size and -20.9 ± 3.98 mV as zeta potential. PDI value and transmission electron microscopy result showed the narrow globule size distribution of MMEI. The result showed that all three independent variables had a significant effect (p < 0.05) on the responses. Rota-rod and open-field test findings revealed the significant improvement in motor performance and gross behavioral activity of the mice. The results from in vivo study and immunohistochemistry showed that nasal administration of Ibuprofen significantly reduced the MPTP-mediated dopamine depletion. Furthermore TH neurons count in the substantia nigra and the density of striatal dopaminergic nerve terminals were found to be significant higher for ibuprofen treated groups. CONCLUSION: Findings of the investigation revealed that Ibuprofen through developed MMEI was shown to protect neurons against MPTP-induced injury in the Substantia nigra pars compacta (SNpc) and striatum and hence, could be a promising approach for brain targeting of Ibuprofen through intranasal route to treat PD.

Application of multiple regression analysis in optimization of anastrozole-loaded PLGA nanoparticles.

The present investigation deals with development of anastrozole-loaded PLGA nanoparticles (NPs) as an alternate to conventional cancer therapy. The NPs were prepared by nanoprecipitation method and optimized using multiple regression analysis. Independent variables included drug:polymer ratio (X1), polymer concentration in organic phase (X2) and surfactant concentration in aqueous phase (X3) while dependent variables were percentage drug entrapment (PDE) and particle size (PS). Results of desirability criteria, check point analysis and normalized error were considered for selecting the formulation with highest PDE and lowest PS. Prepared NPs were characterized for zeta potential, transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and in vitro drug release studies. DSC and TEM studies indicated absence of any drug-polymer interaction and spherical nature of NPs, respectively. In vitro drug release showed biphasic pattern exhibiting Fickian diffusion-based release mechanism. This delivery system of anastrozole is expected to reduce the side effects associated with the conventional cancer therapy by reducing dosing frequency.

Glucagon: Delivery advancements for hypoglycemia management.

As the 100th anniversary of glucagon's discovery approaches, we reflect on the remarkable journey of understanding its pivotal role in glucose regulation. Advancements in glucagon delivery systems for managing hypoglycemia are unfolding with promise, albeit accompanied by formulation and implementation challenges. Recent developments include non-injectable methods like BAQSIMI® (Nasal glucagon) offers a user-friendly option, but stability, bioavailability, and rapid onset remain formulation hurdles. Closed-loop systems, combining glucagon with insulin, aim to automate glucose control, demanding stable and precise formulations compatible with complex algorithms. However, achieving co-delivery harmony and effective dual-hormone responses poses substantial challenges. Ogluo® and Gvoke HypoPen® are auto-injector pens, a ready-to-use solution that can rapidly control hypoglycemia and eliminate the need for mixing powder and liquid. GlucaGen® Hypokit® and Glucagon Emergency Kits are traditional deliveries that possess complexity during administration and are still widely used in clinical practice. In addition to this advancement, we have covered the recent patents and clinical trials of glucagon delivery. The synergy of patent innovation and clinical validation offers a glimpse into the transformative potential of glucagon delivery yet underscores the intricate path toward widespread adoption and improved diabetes care. Finally, this review will help the formulation scientist, clinicians, healthcare providers, and patient to manage hypoglycemia using glucagon.

Novel Discoveries and Clinical Advancements for Treating Onychomycosis: A Mechanistic Insight.

Onychomycosis continues to be the most challenging disease condition for pharmaceutical scientists to develop an effective drug delivery system. Treatment challenges lie in incomplete cure and high relapse rate. Present compilation provides cumulative information on pathophysiology, diagnostic techniques, and conventional treatment strategies to manage onychomycosis. Novel technologies developed for successful delivery of antifungal molecules are also discussed in brief. Multidirectional information offered by this article also unlocks the panoramic view of leading patented technologies and clinical trials. The obtained clinical landscape recommends the use of advanced technology driven approaches, as a promising way-out for treatment of onychomycosis. Collectively, present review warrants the application of novel technologies for the successful management of onychomycosis. This review will assist readers to envision a better understanding about the technologies available for combating onychomycosis. We also trust that these contributions address and certainly will encourage the design and development of nanocarriers-based delivery vehicles for effective management of onychomycosis.

Solid lipid nanoparticles and nanosuspension of adefovir dipivoxil for bioavailability improvement: formulation, characterization, pharmacokinetic and biodistribution studies.

The present study was aimed at developing colloidal formulations like solid lipid nanoparticles (SLN) and nanosuspension (NS) for improving bioavailability of adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor which displays poor oral bioavailability. SLNs were prepared by solvent injection method while NS was prepared by pearl milling method. The prepared formulations were characterized for physicochemical parameters such as particle size, ζ potential, drug content, X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC). Pharmacokinetic and biodistribution studies were performed in mice to evaluate in vivo fate of the formulations. The SLNs showed particle size of 267 ± 18 nm and entrapment efficiency of 73.5 ± 2.12%. The particle size obtained for NS was 393 ± 13 nm against 710 ± 70 µm for bulk drug, which led to significant improvement in saturation solubility. DSC and XRD studies of NS and SLN showed reduction in crystallinity while in vitro studies showed improved dissolution rate in both cases. Pharmacokinetics studies of orally administered formulations in mice exhibited higher plasma concentration compared to plain drug. Biodistribution studies showed higher accumulation of drug in liver, kidneys, intestine and stomach. The higher concentration of AD in liver after 24 hr highlights its potential advantage for effective treatment of chronic hepatitis infection. The relative bioavailability for adefovir NS and SLN were 52.46% and 78.23% respectively compared to 34.34% bioavailability obtained after administration of adefovir micro suspension (AMS), indicating suitability of both nanoparticulate formulations for improving bioavailability. SLNs were found to performed better as compared to NS for improving the bioavailability of AD.

Bioavailability enhancement of baclofen by gastroretentive floating formulation: statistical optimization, in vitro and in vivo pharmacokinetic studies.

OBJECTIVES: The study was aimed to improve bioavailability of baclofen by developing gastroretentive floating drug delivery system (GFDDS). METHODS: Preliminary optimization was done to select various release retardants to obtain minimum floating lag time, maximum floating duration and sustained release. Optimization by 3(2) factorial design was done using Polyox WSR 303 (X1) and HPMC K4M (X2) as independent variables and cumulative percentage drug released at 6 h (Q6h) as dependent variable. RESULTS: Optimized formulation showed floating lag time of 4-5 s, floated for more than 12 h and released the drug in sustained manner. In vitro release followed zero ordered kinetics and when fitted to Korsemeyer Peppas model, indicated drug release by combination of diffusion as well as chain relaxation. In vivo floatability study confirmed floatation for more than 6 h. In vivo pharmacokinetic studies in rabbits showed Cmax of 189.96 ± 13.04 ng/mL and Tmax of 4 ± 0.35 h for GFDDS. The difference for AUC(0-T) and AUC(0-∞) between the test and reference formulation was statistically significant (p > 0.05). AUC(0-T) and AUC(0-∞) for GFDDS was 2.34 and 2.43 times greater than the marketed formulation respectively. CONCLUSION: GFDDS provided prolonged gastric residence and showed significant increase in bioavailability of baclofen.

Simvastatin nanoemulsion for improved oral delivery: design, characterisation, in vitro and in vivo studies.

Simvastatin is poorly bioavailable as it is practically insoluble in water and shows dissolution rate-limited absorption. Therefore, the present study was aimed at preparing nanoemulsion (NE) of simvastatin for improving its solubility and/or dissolution rate for enhancing its bioavailability. The NEs were evaluated for particle size (PS), zeta potential, transmission electron microscopy (TEM), viscosity, in vitro release and stability studies. The optimised NE showed PS of 132 ± 9 nm and zeta potential of 17.1 ± 1.2 mV. TEM studies demonstrated spherical shape and size of the globules. In vitro release studies showed increased dissolution rate of NE compared with plain drug (PD). Pharmacokinetic studies showed relative bioavailability of simvastatin NE was 369.0% with respect to PD suspension. Pharmacodynamic studies conducted in hyperlipidemic rats showed that significant decrease in the total cholesterol and triglyceride levels for NE as compared with PD proving improvement in bioavailability. In conclusion, NE has great potential for improving bioavailability of poorly water-soluble drugs like simvastatin.

Intracellular delivery of etoposide loaded biodegradable nanoparticles: cytotoxicity and cellular uptake studies.

The preferred delivery systems for anticancer drugs would be the one which would have selective and effective destruction of cancer cells. In the present study etoposide (ETO) loaded nanoparticles (NP) were prepared using PLGA (ETO-PLGA NP), PLGA-MPEG block copolymer (ETO-PLGA-MPEG NP) and PLGA-Pluronic copolymer (ETO-PLGA-PLU NP) and they were evaluated for cytotoxicity and cellular uptake studies using two cancer cell lines, L1210 and DU145. The IC50 values for L1210 cells were 18.0, 6.2, 4.8 and 5.4 microM and for DU145 cells the IC50 values were 98.4, 75.1, 60.1 and 71.3 microM for ETO, ETO-PLGA NP, ETO-PLGA-MPEG NP and ETO-PLGA-PLU NP respectively. The increased cytotoxicities were attributed to increased uptake of the NPs by the cells. Moreover the ETO loaded PLGA-MPEG NP and PLGA-Pluronic NP showed a sustained cytotoxic effect till 5 days on both the cell lines. Results of the long term cytotoxicity study concluded that the drug loaded PLGA nanoparticulate formulations were efficient in decreasing the viability of the L1210 cells over a period of three days, whereas the pure drug exerted its maximum efficiency on the day one itself. Z-stack confocal images of NPs showed fluorescence activity in each section of DU 145 and L1210 cells indicating that the nanoparticles were internalized by the cells. The study concluded that ETO loaded PLGA NPs had higher cytotoxicity compared with that of the free drug and ETO-PLGA-MPEG NP and ETO-PLGA-PLU NP had higher cell uptake efficiency compared with that of ETO-PLGA NP. The developed PLGA based NPs shows promise to be used for cancer therapy.

Solid lipid nanoparticles and nanosuspension formulation of Saquinavir: preparation, characterization, pharmacokinetics and biodistribution studies.

Solid lipid nanoparticles (SLNs) and nanosuspensions (NSs) have shown great promise for improving bioavailability of poorly water-soluble drugs. This study was aimed to develop SLNs and NS of Saquinavir (SQ) for improvement in bioavailability. These formulations were characterized and their pharmacokinetics and biodistribution in mice were evaluated. Saquinavir-loaded SLNs (SQSLNs) showed particle size 215 ± 9 nm and entrapment efficiency 79.24 ± 1.53%, while solid-state studies (differential scanning calorimetry and X-ray diffraction) indicated entrapment of the drug in SLNs. Saquinavir NS (SNS) showed particle size 344 ± 16 nm with fourfold increase in saturation solubility and its solid-state studies showed reduction in crystallinity. Pharmacokinetics and biodistribution studies of orally administered SQSLN and SNS in mice exhibited higher plasma level concentration compared to saquinavir microsuspension (SMS). The relative bioavailabilities for SNS and SQSLN were 37.39% and 66.53%, respectively, compared to 18.87% bioavailability obtained after administration of SMS, indicating suitability of nanoparticulate formulations for improving bioavailability.

Long circulating PEGylated PLGA nanoparticles of cytarabine for targeting leukemia.

The present investigation was aimed at developing PEGylated PLGA nanoparticles of cytarabine. PLGA Nanoparticles were prepared by modified nanoprecipitation method, optimized for mean particle size (152 ± 6 nm) and entrapment efficiency (41.1 ± 0.8%) by a 3² factorial design. The PEGylated PLGA nanoparticles of cytarabine had a zeta potential of -7.5 ± 1.3 mV and sustained the release of cytarabine for 48 h by Fickian diffusion. The IC50 values for L1210 cells were 6.5, 5.3, and 2.2 µM for cytarabine, cytarabine loaded PLGA nanoparticles and cytarabine loaded PLGA-mPEG nanoparticles respectively. Confocal microscopy and flow cytometry showed that the nanoparticles were internalized by the L1210 cells and not simply bound to their surface. Biodistribution studies showed that the PEGylated nanoparticles of cytarabine were present in significantly higher concentrations in blood circulation as well as in brain and bones and avoided RES uptake as compared to the free drug.

Chondroitin sulfate conjugation facilitates tumor cell internalization of albumin nanoparticles for brain-targeted delivery of temozolomide via CD44 receptor-mediated targeting.

In the present investigation, temozolomide (TMZ) loaded chondroitin sulfate conjugated albumin nanoparticles (CS-TNPs) were fabricated by desolvation method were chondroitin sulfate (CS) was used as the surface exposed ligand to achieve CD44 receptor mediated targeting of brain tumor. The developed CS-TNPs were characterized for particle size, zeta potential, entrapment efficiency and drug loading and evaluated by FTIR, DSC, XRD and TEM analysis. BBB (blood brain barrier) passage study using in vitro BBB model indicated that CS-TNPs were able to efficiently cross the BBB. Cell viability assay data demonstrated higher cytotoxicity of CS-TNPs as compared with pure TMZ. The CD44 receptor blocking assay and receptor poisoning assay in U87 MG cells confirmed the CD44 receptor and endocytosis-mediated (caveolae pathway) uptake of CS-TNPs. CS-TNPs were able to generate ROS in U87 MG cells. In vivo pharmacokinetic and biodistribution studies were performed in Wistar rats. In vivo results revealed significant enhancement in pharmacokinetic profile of CS-TNPs as compared with TMZ alone. Biodistribution results demonstrated higher accumulation of TMZ in the brain by CS-TNPs as compared with the pure drug that confirmed the brain targeting ability of nanoparticles. From all obtained results, it may be concluded that CS-TNPs are promising carrier to deliver TMZ to the brain for targeted therapy of brain tumor. Graphical abstract.

An Overview of Nanocarrier-Based Adjuvants for Vaccine Delivery.

The development of vaccines is one of the most significant medical accomplishments which has helped to eradicate a large number of diseases. It has undergone an evolutionary process from live attenuated pathogen vaccine to killed whole organisms or inactivated toxins (toxoids), each of them having its own advantages and disadvantages. The crucial parameters in vaccination are the generation of memory response and protection against infection, while an important aspect is the effective delivery of antigen in an intelligent manner to evoke a robust immune response. In this regard, nanotechnology is greatly contributing to developing efficient vaccine adjuvants and delivery systems. These can protect the encapsulated antigen from the host's in-vivo environment and releasing it in a sustained manner to induce a long-lasting immunostimulatory effect. In view of this, the present review article summarizes nanoscale-based adjuvants and delivery vehicles such as viral vectors, virus-like particles and virosomes; non-viral vectors namely nanoemulsions, lipid nanocarriers, biodegradable and non-degradable nanoparticles, calcium phosphate nanoparticles, colloidally stable nanoparticles, proteosomes; and pattern recognition receptors covering c-type lectin receptors and toll-like receptors.

Modified nanoprecipitation method for preparation of cytarabine-loaded PLGA nanoparticles.

The present investigation was aimed at developing cytarabine-loaded poly(lactide-coglycolide) (PLGA)-based biodegradable nanoparticles by a modified nanoprecipitation which would have sustained release of the drug. Nine batches were prepared as per 3(2) factorial design to optimize volume of the co-solvent (0.22-0.37 ml) and volume of non-solvent (1.7-3.0 ml). A second 3(2) factorial design was used for optimization of drug: polymer ratio (1:5) and stirring time (30 min) based on the two responses, mean particle size (125 ± 2.5 nm), and percentage entrapment efficiency (21.8 ± 2.0%) of the Cyt-PLGA nanoparticles. Optimized formulation showed a zeta potential of -29.7 mV indicating good stability; 50% w/w of sucrose in Cyt-PLGA NP was added successfully as cryoprotectant during lyophilization for freeze-dried NPs and showed good dispersibility with minimum increase in their mean particle sizes. The DSC thermograms concluded that in the prepared PLGA NP, the drug was present in the amorphous phase and may have been homogeneously dispersed in the PLGA matrix. In vitro drug release from the pure drug was complete within 2 h, but was sustained up to 24 h from PLGA nanoparticles with Fickian diffusion. Stability studies showed that the developed PLGA NPs should be stored in the freeze-dried state at 2-8°C where they would remain stable in terms of both mean particle size and drug content for 2 months.