Modified Solvent Evaporation Technique Research Articles

Paclitaxel loaded Capmul MCM and tristearin based nanostructured lipid carriers (NLCs) for glioblastoma treatment: screening of formulation components by quality by design (QbD) approach.

Paclitaxel (PTX), a naturally occurring diterpenoid isolated from Taxus brevifolia, is a first-line drug for the treatment of glioblastoma; however, it suffers from the disadvantages of poor water solubility and nonspecific biodistribution, which cause serious side effects in the human body. The marketed formulation suffers from serious side effects, such as allergic reactions, neutropenia, and neuropathy, which require safe and effective formulations of PTX. In the present study, PTX was entrapped in a solid-liquid lipid mixture with the aid of a surfactant using a modified solvent evaporation technique. Higher entrapment of the impressive stability of the formulation was achieved by employing quality design-based strategies. Optimized levels by employing a numerical optimization technique for each factor, that is, surfactant concentration (X1), lipid concentration (X2), and amount of organic solvent (X3) were 0.3%, 0.76% & 8.3 ml respectively. The resultant formulation exhibited a particle size of 121.44 nm, entrapment efficiency of 94.27%, and zeta potential of -20.21 mV with unimodal size distribution. A reduction in the % crystalline index from 48 to 3.4% ensured the amorphous form of the entrapped drug inside the formulation, which precludes the fear of leakage and instability of the formulation. Cell line studies conducted on U87MG Cell lines also suggested that the NLC of paclitaxel are more effective than those of pure PTX. In summary, PTXNLC seem to be a superior alternative carrier system for the formulation industry to obtain higher entrapment with excellent stability.

Natural Polymer-Based Nanogel for pH-Responsive Delivery of Sorafenib Tosylate in Hemangiosarcoma.

Smart nanomedicinal treatment for cancer manifests a solubility challenge with inherent nanoscale size and nonspecific release with stimuli-responsive potential. This is the limelight in novel chemotherapy to pursue physiochemical differences between the tumor microenvironment (TME) and normal cells, which introduces active groups of nanocarriers responding to various stimuli, endowing them with concise responses to various tumor-related signals. The nanogels were successfully prepared by a modified solvent evaporation technique. Nine batches were formulated by changing the chitosan concentration (12, 14, 16mg/ml) and sonication time (5, 10, 15min). The formulations were optimized for particle size and zeta potential with high percent entrapment efficiency (%EE) through Central Composite Design software. The optimized batch F7 had a 182-nm size and high zeta potential (64.5mV) with 98% EE. The drug release of F7 was higher at pH 6 (97.556%) than at pH 7.4 (45.113%). The pharmacokinetic study shows that the release follows the Hixon plot model (R2 = 0.9334) that shifts to zero order (R2 = 0.9149). The nanogel F7 was observed for stability and showed an absence of color change, phase separation, and opacity for 6months. In the present study, the pH difference between cancer cells and normal cells is the key point of the smart nanogel. This study is promising but challenging depending on the in vivo study. The nanogel was successfully prepared and evaluated for pH-responsive release. As hemangiosarcoma commonly occurs in dogs, this formulation helps to limit the difficulties with administration.

Improving Infection Resistance in Tissue Engineered Scaffolds for Tensile Applications Using Vancomycin‐Embedded Melt Electrowritten Scaffolds

AbstractIt is important to consider mechanical, biological, and antibacterial properties of scaffolds when used for tissue engineering applications. This study presents a method to create complex “wavy” architecture polycaprolactone (PCL) scaffolds toward the development of tissue engineered ligament and tendon tissue substitutes, fabricated using melt electrowriting (MEW) and loaded with vancomycin (5, 10, and 25% w/w). Scaffolds are characterized for both mechanical and biological properties. Loading PCL scaffolds with vancomycin with modified solvent evaporation technique achieves a high loading efficiency of maximum 18% w/w and high encapsulation efficiency with over 89%. Vancomycin loaded PCL scaffolds with all three doses (5, 10, and 25% w/w) display antibacterial activity against Gram‐positive Staphylococcus aureus (S. aureus) up to 14 days of release. Initial burst followed by a sustained release is observed on all three vancomycin loaded scaffolds for up to 28 days. Importantly, in addition to antibacterial properties, vancomycin‐loaded PCL scaffolds also display improved mechanical properties compared to traditional crosshatch design MEW scaffolds and are noncytotoxic at all concentrations as demonstrated by live‐dead staining, cell attachment and proliferation assays indicating its potential as an effective treatment option for tissue regeneration in rotator cuff injuries or other tissues undergoing tensile biomechanical loading.

Development of a liquid chromatography-tandem mass spectrometry method for the analysis of docetaxel-loaded Poly(lactic-co-glycolic acid) nanoparticles

Docetaxel is among the most effective chemotherapeutic agents used for the treatment of solid tumors, such as breast cancer. Targeting docetaxel to the tumor site would increase the safety and efficacy of the treatment. The focus of this work was to develop an efficient liquid chromatography tandem mass spectrometry (LC-MS/MS) method to quantify docetaxel entrapped in optimized poly lactic-co-glycolic acid (PLGA) nanoparticles. Several nanoparticle formulations were prepared to optimize the nanoparticles based on their size and yield percentage using a modified solvent evaporation technique. The MS/MS fingerprints of docetaxel and paclitaxel (as internal standard) were used to identify diagnostic product ion for developing a multiple reaction monitoring (MRM) LC-MS/MS method for the quantification of docetaxel in the PLGA nanoparticles. A triple quadrupole linear ion trap instrument (AB Sciex 4000 QTRAP) equipped with electrospray ionization was used. The optimized nanoparticles had a zeta potential of −23.2 ± 1.4 mV and mean particle sizes of 202.2 ± 4.7 nm and 251.7 ± 8.2 nm before and after freeze-drying, respectively. Polydispersity index values of the nanoparticles confirmed their uniform size distribution. The developed LC-MS/MS method could quantify docetaxel in the PLGA matrix with accuracy and precision covering a broad linear range of 15.6–4000 ng/mL. Method validation was conducted using the regulatory guidelines of the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and showed acceptable values for all the tested criteria. The developed LC-MS/MS method with the novelty of using a phenyl column will be beneficial for future analysis of docetaxel loaded polymeric nano-delivery systems.

Formulation Development and Characterization of pH Responsive Polymeric Nano-Pharmaceuticals for Targeted Delivery of Anti-Cancer Drug (Methotrexate).

Oral administration of pH sensitive/stimuli responsive nanoparticles are gaining importance because of the limited side effects, minimum dose and controlled drug release. The objective of this study was to develop and evaluate pH sensitive polymeric nanoparticles for methotrexate with the aim to maximize the drug release at target site. In the presented study, pH sensitive polymeric nanoparticles of methotrexate were developed through modified solvent evaporation technique using polymer Eudragit S100. Different process parameters like drug to polymer ratio, speed of sonication, concentration of surfactant and time of sonication were optimized by evaluating their effects on particle size, PDI, zeta potential, entrapment/encapsulation efficiency. The developed formulations were evaluated for their size, polydispersity (PDI), zeta potential, encapsulation efficiency, XRD, scanning electron microscopy, in-vitro drug release and stability studies. Best results were obtained with poloxamer-407 and PVA and were selected as surfactants. Physicochemical characterization of the developed formulations showed that the particle size lies in the range 165.7 ± 1.85–330.4 ± 4.19, PDI 0.119 ± 0.02–0.235 ± 0.008, zeta potential −0.163 ± 0.11–−5.64 ± 0.36 mV, and encapsulation efficiency more than 61%. The results of scanning electron microscopy revealed that nanoparticles have regular geometry with spherical shape. Initially the drug release occur through diffusion followed by erosion. The present studies showed that MTX-ES100 nanoparticles prepared during this study have the desired physicochemical properties, surface morphology and release characteristics used to target the desired organs.

Effects of curcumin-loaded poly(lactic-co-glycolic acid) nanoparticles in MDA-MB231 human breast cancer cells.

Aim: This study was aimed at evaluating the anticancer potential of curcumin-loaded poly(lactic-co-glycolic acid) (PLGA) based nanoparticles (NPs) in MDA-MB231 human breast cancer cells. Methods: Curcumin-loaded PLGA NPs were developed using a modifiedsolvent evaporation technique. Physical characterization was performed on the formulated NPs. Furthermore, in vitro experiments were conducted to study the biological activity of the curcumin-loaded NPs. Results: Curcumin-loaded PLGA NPs demonstrated high encapsulation efficiency and sustained payload release. Moreover, the NPs exhibited a significant reduction in cell viability, cell migration and cell invasion in the MDA-MB231 cells. Conclusion: The study revealed that the formulated curcumin-loaded PLGA NPs possessed significant anti-metastatic properties. The findings showcased the possible potential of curcumin-loaded NPs in the management of debilitating conditions such as cancer. In addition, this study could form the basis for further research and advancements in this area.

Characterization of Citrusnobilis Peel Methanolic Extract for Antioxidant, Antimicrobial, and Anti-Inflammatory Activity.

Currently, the potential utilization of fruits and vegetable waste as a source of micronutrients and antioxidants has increased. The present study, therefore, aimed to determine the antimicrobial and anti-inflammatory activities of Citrus nobilis peel extract. A modified solvent evaporation technique was employed for peel extract preparation. For effective utilization of the natural product, quantitative analysis of phenolic compounds was carried out using liquid chromatography and mass spectroscopy technique. Phenolic and flavonoids were present in high amounts, while β-carotene and lycopene were present in vestigial amounts. The antimicrobial efficiency of peel extract was evaluated against four bacterial strains including Staphylococcus aureus (MTCC 3160), Klebsiella pneumoniae (MTCC 3384), Pseudomonas aeruginosa (MTCC 2295), and Salmonella typhimurium (MTCC 1254), and one fungal strain Candida albicans (MTCC 183), and zone of inhibition was comparable to the positive control streptomycin and amphotericin B, respectively. The extract of Citrus nobilis peels showed effective anti-inflammatory activity during human red blood cell membrane stabilization (HRBC) and albumin denaturation assay. The extracts also exhibited 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity ranging from 53.46 to 81.13%. Therefore, the obtained results suggest that Citrus nobilis peel could be used as an excellent source of polyphenols and transformed into value-added products.

ENHANCEMENT OF THERAPEUTIC WINDOW OF METFORMIN HYDROCHLORIDE BY FABRICATION OF MICROSPHERES COMPRISING POLYMERIC INCULCATION WITH SEMI-SYNTHETIC AND SYNTHETIC POLYMERS BY IMPLEMENTATION OF BOX-BEHNKEN DESIGN

Objective: Innovative enhancement of therapeutic window of Metformin hydrochloride (MFH) and bioavailability through mucoadhesive microspheres by polymeric inculcation of hydroxypropyl methylcellulose K4M grade (HPMC K4M), hydroxypropyl methylcellulose K100M grade (HPMC K100M) and Kollidon SR grade (KS).
 Methods: Controlled release system was developed by incorporating semi-synthetic and synthetic polymers by modified solvent evaporation technique. Fabrication of mucoadhesive microspheres was designed by the implementation of experimental designs to obtain most optimum concentration of selected factors. The method was optimized by Box Behnken design (BBD) with selected factors as concentrations of semi-synthetic and synthetic polymer with stirring speed influence for the obtained responses that were mean particle size (Y1) entrapment efficiency of drug (Y2) and percent mucoadhesion (Y3). Microspheres were characterized for particle size, entrapment efficiency of drug, ex-vivo mucoadhesion study, in vitro study, Fourier transform infrared spectroscopy (FTIR), x-ray diffraction (XRD) detection and H1 Nuclear magnetic resonance (NMR) quantification for optimized formulation.
 Results: Implementation of response surface method software for BBD yielded stable microspheres with mean particle size 274 µm, entrapment efficiency of drug 85.07% and percent mucoadhesion 67.03% for optimized formulation F5.
 Conclusion: Bridging of MFH with the highly innovative combination of semi-synthetic and synthetic polymers yielded stable, cost-effective microspheres with improved bioavailability with controlled-release effect as till date no literature is available that provide information with selected polymeric combination and analytical characterization.

Biodegradable Hypericin-Containing Nanoparticles for Necrosis Targeting and Fluorescence Imaging.

Necrosis targeting and imaging has significant implications for evaluating tumor growth, therapeutic response, and delivery of therapeutics to perinecrotic tumor zones. Hypericin is a hydrophobic molecule with high necrosis affinity and fluorescence imaging properties. To date, the safe and effective delivery of hypericin to areas of necrosis in vivo remains a challenge because of its incompatible biophysical properties. To address this issue, we have developed a biodegradable nanoparticle (Hyp-NP) for delivery of hypericin to tumors for necrosis targeting and fluorescence imaging. The nanoparticle was developed using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) and hypericin by a modified solvent evaporation technique. The size of Hyp-NP was 19.0 ± 1.8 nm from cryo-TEM and 37.3 ± 0.7 nm from dynamic light-scattering analysis with a polydispersity index of 0.15 ± 0.01. The encapsulation efficiency of hypericin was 95.05% w/w by UV-vis absorption. After storage for 30 days, 91.4% hypericin was retained in Hyp-NP with nearly no change in hydrodynamic size, representing nanoparticle stability. In an ovarian cancer cell line, Hyp-NP demonstrated cellular internalization with intracellular cytoplasmic localization and preserved fluorescence and necrosis affinity. In a mouse subcutaneous tumor model, tumor accumulation was noted at 8 h postinjection, with near-complete clearance at 96 h postinjection. Hyp-NP was shown to be tightly localized within necrotic tumor zones. Histological analysis of harvested organs demonstrated no gross abnormalities, and in vitro, no hemolysis was observed. This proof-of-concept study demonstrates the potential clinical applications of Hyp-NP for necrosis targeting.

<p>Engineering of Naproxen Loaded Polymer Hybrid Enteric Microspheres for Modified Release Tablets: Development, Characterization, in silico Modelling and in vivo Evaluation</p>

BackgroundNaproxen (NP) is a non-steroidal anti-inflammatory drug with poor aqueous solubility and low oral bioavailability, which may lead to therapeutic failure. NP causes crucial GIT irritation, bleeding, and peptic and duodenal ulcers.Purpose of the studyThis study aimed to engineer and characterize polymer hybrid enteric microspheres using an integrated (experimental and molecular modelling) approach with further development to solid dosage form with modified drug release kinetics and improved bioavailability.Materials and methodsNP loaded polymer hybrid enteric microspheres (PHE-Ms) were fabricated by using a modified solvent evaporation technique coupled with molecular modelling (MM) approach. The PHE-Ms were characterized by particle size, distribution, morphology, crystallinity, EE, drug-polymer compatibility, and DSC. The optimized NP loaded PHE-Ms were further subjected to downstream procedures including tablet dosage form development, stability studies and comparative in vitro-in vivo evaluation.ResultsThe hydrophobic polymer EUD-L100 and hydrophilic polymer HPMC-E5 delayed and modified drug release at intestinal pH while imparting retardation of NP release at gastric pH to diminish the gastric side effects. The crystallinity of the NP loaded PHE-Ms was established through DSC and P (XRD). The particle size for the developed formulations of PEH-Ms (M1-M5) was in the range from 29.06 ±7.3–74.31 ± 17.7 μm with Span index values of 0.491–0.69, respectively. The produced NP hybrid microspheres demonstrated retarded drug release at pH 1.2 and improved dissolution at pH 6.8. The in vitro drug release patterns were fitted to various release kinetic models and the best-followed model was the Higuchi model with a release exponent “n” value > 0.5. Stability studies at different storage conditions confirmed stability of the NP loaded PHE-Ms based tablets (P<0.05). The molecular modelling (MM) study resulted in adequate binding energy of co-polymer complex SLS-Eudragit-HPMC-Naproxen (−3.9 kcal/mol). In contrast to the NP (unprocessed) and marketed formulations, a significant increase in the Cmax of PHE-MT1 (44.41±4.43) was observed.ConclusionThe current study concludes that developing NP loaded PHE-Ms based tablets could effectively reduce GIT consequences with restored therapeutic effects. The modified release pattern could improve the dissolution rate and enhancement of oral bioavailability. The MM study strengthens the polymer-drug relationship in microspheres.

Central composite designed ezetimibe solid dispersion for dissolution enhancement: synthesis and in vitro evaluation.

Aim: The current research is focused on increasing aqueous solubility and dissolution of BCS class II drug by using modified solvent evaporation technique to produce solid dispersions of ezetimibe (EZSD) using gelucire 50/13 and polyvinyl pyrollidone K30. Methodology & results: Central composite design analyzed the effect of gelucire 50/13 and polyvinyl pyrollidone K30 on the percentage of drug released in 5 and 30min. Ezetimibe (EZ) aqueous saturation solubility (4.56±0.94μg/ml) was increased 25-fold in EZSD (115±3.41μg/ml). Cumulative drug release from EZ and optimized EZSD were observed 24.67 and 87.54% within 1h, respectively. Conclusion: Manufacturing EZSD using modified solvent evaporation technique using rotary evaporator holds great promise for enhancing EZ's solubility and dissolution.

Modified solvent evaporation technique for purpose and categorization of Novel Floating Microspheres of Metronidazole: Optimization of pharmacokinetics, in-vitro and stability study using special process capricious like Emulsifier concentration, stirring rate

Modified solvent evaporation technique for purpose and categorization of Novel Floating Microspheres of Metronidazole: Optimization of pharmacokinetics, in-vitro and stability study using special process capricious like Emulsifier concentration, stirring rate

Preparation and Characterization of Loperamide-Loaded Dynasan 114 Solid Lipid Nanoparticles for Increased Oral Absorption In the Treatment of Diarrhea.

The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN) formulations for oral delivery of loperamide (LPM) to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114) nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a high ratio rate of lipid to drug) and LPM-SLN-2 (LPM-SLN with a low ratio rate of lipid to drug), were prepared by the solvent evaporation method. A change in the lipid concentration affects the characteristics of LPM-SLNs. The average sizes of the LPM-SLNs were 303 ± 18 nm and 519 ± 36 nm, separately, as analyzed by dynamic light scattering. The LPM-SLNs were found to be round with a smooth surface, as observed using a transmission electron microscope and a scanning electron microscope. The average encapsulation efficiencies were 87 ± 3.78% w/w and 84 ± 5.17%, accordingly. In the in vitro release experiments, LPM-SLNs showed a continuous release profile of LPM without any burst release. The oral bioavailability of LPM-SLNs was analyzed using Wistar rats. The relative bioavailabilities of LPM-SLNs were 227 and 153%, respectively, as compared that of the LPM tablet. There was no difference in the Tmax between LPM-SLN-2 and the LPM tablet. In conclusion, LPM-SLN-1 significantly improved the oral bioavailability of LPM, while LPM-SLN-2 having the same swift action as the LPM tablet. These results demonstrate the potential of LPM-SLNs in the oral delivery of LPM to treat different types of diarrhea.

Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: A co-surfactant study

The purpose of this study was to evaluate the effect of process (homogenization speed and evaporation time) and formulation (aqueous/organic phase ratio, surfactant concentration, polymer type and concentration, and drug amount) variables on the preparation of paclitaxel-loaded biodegradable polymeric nanoparticles using modified solvent evaporation technique. Thereafter, a formulation was selected and subjected to evaluation of inclusion of a co-surfactant for further reduction of particle size. Particle size, encapsulation efficiency and in-vitro drug release kinetics were evaluated. It was observed that the inclusion of vitamin E TPGS (0.01%), Poloxamer 188 (0.5%) or Tween 80 (0.25%) reduced the particle size of nanoparticles to 230, 244 or 301 nm from 438 nm, respectively. Encapsulation efficiency increased for both vitamin E TPGS and Poloxamer 188 up to concentration at 0.010% and 0.25%, respectively, while this was not the case for Tween 80. Comparison of drug release kinetics demonstrated that drug release accelerated from paclitaxel-loaded biodegradable nanoparticles prepared with the inclusion of Tween 80 but was delayed for Poloxamer 188 and vitamin E TPGS. Thus, it was concluded that the particle size of the nanoparticles could be reduced further and the paclitaxel release kinetics could easily be adjusted by taking advantage by the inclusion of a co-surfactant.

Development and In vitro Evaluation of Flurbiprofen Microcapsules Prepared by Modified Solvent Evaporation Technique

Purpose: To develop modified release microcapsules of flurbiprofen for sustained release and reduced gastrointestinal side effects.Method: A co-polymer containing Eudragit RS 100 and hydroxypropyl methylcellulose (HPMC) in different drug/co-polymer ratios was used for microencapsulation of flurbiprofen by modified emulsion solvent evaporation (MESE) technique. The microcapsules were evaluated by x-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FTIR) and scanning electron microscopy (SEM). Dissolution study was conducted in 0.1 M HCl for 2 h and phosphate buffer (pH 7.4) for 8 h, and the resulting data were analyzed by various pharmacokinetic models.Results: The data obtained from pre-formulation confirmed the purity of flurbiprofen. Particle size, flow rate and angle of repose showed good flow properties. FTIR and DSC confirmed the absence of incompatibilities among the drug and polymers. XRD of flurbiprofen showed characteristic sharp peaks confirming the crystalline nature of the drug which, however, decreased slightly in the formulation. SEM revealed that microencapsules of spherical shape and rough surface were produced at lower drug to copolymer ratio in contrast to the higher ratio which produced irregular microcapsules. Encapsulation efficiency was 65 - 85 % while regression coefficient (R2) values from kinetic analysis showed thatrelease followed Korsmeyer-Peppas model with “n” &gt; 1 indicating release mechanism followed super case II transport.Conclusion: MESE technique using Eudragit RS 100/HPMC polymer blend is a suitable approach to development of modified release flurbiprofen microcapsules.Keywords: Microcapsules, Eudragit RS-100, Hydroxypropyl methylcellulose, Emulsion solvent evaporation, Flurbiprofen, Sustained drug release

Formulation and evaluation of novel stomach specific floating microspheres bearing famotidine for treatment of gastric ulcer and their radiographic study

ABSTRACT Objective To develop and characterize multiple-unit-type oral floating microsphere of famotidine to prolong gastric residence time and to target stomach ulcer. Methods The floating microspheres were prepared by modified solvent evaporation method. Eudragit S-100 was used as polymer. Microspheres were characterized for the micromeritic properties, floating behavior, entrapment efficiency and scanning electron microscopy. The in-vitro release studies and floating behavior were studied in simulated gastric fluid at pH 1.2. Different drug release kinetics models were also applied for all the batches. Selected formulations were also subjected for X-ray radiographic study. Results Floating microspheres were successfully prepared by modified solvent evaporation technique. Microspheres showed passable flow properties. The maximum yield of microspheres was up to (95.11±0.35)%. On the basis of optical microscopy particle size range was found to be ranging from (52.18±182.00) to (91.64±5.16) μm. Scanning electron microscopy showed their spherical size, perforated smooth surface and a cavity inside microspheres. Microspheres were capable to float up to 20 h in simulated gastric fluid. X-ray radiographic studies also proved its better retention in the stomach. Conclusions On the basis of the results, such dosage forms may be a good candidate for stomach targeting and may be dispensed in hard gelatin capsules.

Development and characterization of novel site specific hollow floating microspheres bearing 5-Fu for stomach targeting.

Multiple-unit-type oral floating hollow microspheres of 5-fluorouracil (5-Fu) were developed using modified solvent evaporation technique to prolong gastric residence time, to target stomach cancer, and to increase drug bioavailability. The prepared microspheres were characterized for micromeritic properties, floating behavior, entrapment efficiency, and scanning electron microscopy (SEM). The in vitro drug release and floating behavior were studied in simulated gastric fluid (SGF) at pH 1.2. The yield of microspheres was obtained up to 84.46 ± 6.47%. Microspheres showed passable flow properties. Based on optical microscopy, particle size was found to be ranging from 158.65 ± 12.02 to 198.67 ± 17.45 μm. SEM confirmed spherical size, perforated smooth surface, and a hollow cavity inside the microspheres. Different kinetic models for drug release were also applied on selected batches.

Chemoprevention of pancreatic cancer using solid-lipid nanoparticulate delivery of a novel aspirin, curcumin and sulforaphane drug combination regimen

Pancreatic cancer is the fourth largest cause of cancer deaths in the Unites States and the prognosis is grim with <5% survival chances upon diagnosis. The objective of this study was to assess the combined chemopreventive effect of solid lipid nanoparticle (SLN) encapsulated drugs aspirin (ASP), curcumin (CUR) and free sulforaphane (SFN) for the chemoprevention of pancreatic cancer. Experiments were carried out (1) to evaluate the feasibility of encapsulation of these chemopreventive agents within solid lipid systems and (2) to measure the synergistic effects of a combination of ASP with CUR in SLNs mixed with free SFN against cell proliferation and apoptosis in pancreatic cancer cells, MIA PaCa-2 and Panc-1. The SLNs were prepared using a modified solvent evaporation technique and were characterized for particle sizing, encapsulation efficiency and drug release. ASP and CUR SLNs were formulated within the particle size range of 150–250 nm and were found to have an encapsulation efficiency of 85 and 69%, respectively. Sustained release of drugs over a 96 h period from SLNs was observed. The SLNs were stable over a 3-month storage period at room temperature. Cell viability studies demonstrated that combinations of low doses of ASP SLN (25 μM), CUR SLN (2.5 μM) and free SFN (5 μM) significantly reduced cell viability by 43.6 and 48.49% in MIAPaca-2 and Panc-1 cell lines, respectively. Furthermore, increased apoptosis of 61.3 and 60.37% was found in MIA Paca-2 and Panc-1 cell lines, respectively, in comparison to the individual doses administered. Synergistic effects were demonstrated using MTS and apoptosis assays. Thus, this study successfully demonstrated the feasibility of using a solid lipid nanoparticulate system for the first time to deliver this novel combination chemoprevention regimen, providing valuable evidence for the usability of nanotechnology-based drug regimens towards pancreatic cancer chemoprevention.

Production and Characterization of Anisotropic Particles from Biodegradable Materials

In recent years, production and characterization of anisotropic particles has become of interest in a wide range of scientific fields including polymer chemistry, drug delivery, electronics, energy, and nanotechnology. In this work, we demonstrate a novel formulation for production of anisotropic particles via an internal phase separation of biodegradable components. Specifically, binary mixtures of biodegradable polymers poly(lactic-co-glycolic acid), polycaprolactone, and biodegradable lipid Precirol (glyceryl palmitostearate) were dissolved in dichloromethane, emulsified, and prepared into anisotropic particles using a modified solvent evaporation technique. During the slow evaporation process the components self-assembled into anisotropic particles with distinct morphologies. Polymer/polymer formulations resulted in compartmentalized anisotropic heterodimer particles, while polymer/lipid combinations yielded "ice cream cone" shaped particles. It was found that addition of certain active pharmaceuticals resulted in an altered, pox-like segregation at the particle surface of polymer/polymer formulations. The anisotropic nature of the particles was subsequently characterized using optical microscopy, scanning electron microscopy, zeta potential, electrophoresis, and X-ray diffraction. Successful formulations presented here may potentially be employed as multicompartmental drug carriers with staggered drug release rates or alternatively as a colloidal excipient for an arsenal of pharmaceutical applications.

Preparation and characterization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHX) based nanoparticles for targeted cancer therapy

Targeted drug delivery systems are one of the most promising alternatives for the cancer therapy. Rapid developments on nanomedicine facilitated the creation of novel nanotherapeutics by using different nanomaterials. Especially polymer based nanoparticles are convenient for this purpose. In this study; a natural polymer (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate), PHBHHX) was used as a base matrix for the production of a novel nanotherapeutic including antineoplastic agent, Etoposide and attached folic acid as a ligand on the nanoparticles. Modified solvent evaporation technique was used for the production of PHBHHX nanoparticles and the average size of the obtained PHBHHX nanoparticles were observed in the range of 180 nm and 1.5 μm by the change in experimental conditions (i.e., homogenization rate, surfactant concentration and polymer/solvent ratio). By the increase in homogenization rate and surfactant concentration, size of the nanoparticles was decreased, while the size was increased by the increase in polymer/solvent ratio. Drug loading ratio was also found to be highly affected by polymer/drug ratio. Surface charge of the prepared nanoparticles was also investigated by zeta potential measurements. In the cytotoxicity tests; Etoposide loaded and folic acid attached PHBHHX nanoparticles were observed as more effective on HeLa cells than Etoposide loaded PHBHHX nanoparticles without attached folic acid. The cytotoxicity of folic acid conjugated PHBHHX nanoparticles to cancer cells was found to be much higher than that of normal fibroblast cells, demonstrating that the folate conjugated nanoparticles has the ability to selectively target to cancer cells. In addition, apoptotic/necrotic activities were evaluated for all formulations of the PHBHHX nanoparticles and parallel results with cytotoxicity tests were obtained. These studies demonstrate that the folic acid attached and Etoposide loaded PHBHHX nanoparticles seem as promising for the targeted cancer therapy.