Pregnenolone Inhibits Doxorubicin-Induced Cardiac Oxidative Stress, Inflammation, and Apoptosis-Role of Matrix Metalloproteinase 2 and NADPH Oxidase 1.

The clinical usefulness of doxorubicin (DOX) is limited by its serious adverse effects, such as cardiotoxicity. Pregnenolone demonstrated both anti-inflammatory and antioxidant activity in animal models. The current study aimed to investigate the cardioprotective potential of pregnenolone against DOX-induced cardiotoxicity. After acclimatization, male Wistar rats were randomly grouped into four groups: control (vehicle-treated), pregnenolone (35 mg/kg/d, p.o.), DOX (15 mg/kg, i.p, once), and pregnenolone + DOX. All treatments continued for seven consecutive days except DOX, which was administered once on day 5. The heart and serum samples were harvested one day after the last treatment for further assays. Pregnenolone ameliorated the DOX-induced increase in markers of cardiotoxicity, namely, histopathological changes and elevated serum levels of creatine kinase-MB and lactate dehydrogenase. Moreover, pregnenolone prevented DOX-induced oxidative changes (significantly lowered cardiac malondialdehyde, total nitrite/nitrate, and NADPH oxidase 1, and elevated reduced glutathione), tissue remodeling (significantly decreased matrix metalloproteinase 2), inflammation (significantly decreased tumor necrosis factor-α and interleukin 6), and proapoptotic changes (significantly lowered cleaved caspase-3). In conclusion, these findings show the cardioprotective effects of pregnenolone in DOX-treated rats. The cardioprotection achieved by pregnenolone treatment can be attributed to its antioxidant, anti-inflammatory, and antiapoptotic actions.

Enhancement of Anticorrosive Performance of Cardanol Based Polyurethane Coatings by Incorporating Magnetic Hydroxyapatite Nanoparticles.

The present investigation demonstrates renewable cardanol-based polyol for the formulation of nanocomposite polyurethane (PU) coatings. The functional and structural features of cardanol polyol and nanoparticles were studied using FT-IR and 1H NMR spectroscopic techniques. The magnetic hydroxyapatite nanoparticles (MHAPs) were dispersed 1-5% in PU formulations to develop nanocomposite anticorrosive coatings. An increase in the strength of MHAP increased the anticorrosive performance as examined by immersion and electrochemical methods. The nanocomposite PU coatings showed good coating properties, viz., gloss, pencil hardness, flexibility, cross-cut adhesion, and chemical resistance. Additionally, the coatings were also studied for surface morphology, wetting, and thermal properties by scanning electron microscope (SEM), contact angle, and thermogravimetric analysis (TGA), respectively. The hydrophobic nature of PU coatings increased by the addition of MHAP, and an optimum result (105°) was observed in 3% loading. The developed coatings revealed its hydrophobic nature with excellent anticorrosive performance.

Standardization of topical preparations for finger-tip unit-Awareness and attitudes among pharmacists and dermatologists and suggestions to improve standardization of topical drug dosing-A two-phase cross-sectional survey.

BACKGROUND: Standardization of topical therapy dosage is important to ensure optimum use and dosage of topical medications. One of the concepts frequently used in the standardization of topical treatment is the Finger-tip unit (FTU). While practitioners, both dermatologists and pharmacists, are generally aware of FTU, practical use is less. OBJECTIVES: We aimed to evaluate views and practices related to FTU among both dermatology and pharmacy faculty and to elicit and validate suggestions for improving standardization. METHODS: We surveyed a group of Dermatologists and Pharmacists-in two phases-in phase 1 (n = 44), an electronic survey was used as a tool to understand their practices regarding FTU, and to obtain suggestions regarding standardization of topical medication delivery. In phase 2 (n = 40), the main suggestions for improvement were resent to the group to rate and validate the same. RESULTS: The awareness of FTU was high among the experts, but practical use of the FTU for patient counselling was less frequent. The group gave suggestions to standardize applications. All these suggestions got high ratings on both feasibility and possible effectiveness in the second phase, with the highest rating being for the suggestion of "Placing QR codes on ointment/cream tubes which link to websites with educational materials/ videos on FTU/topical drug dosing." CONCLUSION: Awareness regarding FTU is high among both dermatologists and pharmacists, however practical use is less. Strategies to improve standardization of topical drug dosing can be formulated through collaboration involving both dermatologists and pharmacists.

Constant Voltage Iontophoresis Technique to Deliver Terbinafine via Transungual Delivery System: Formulation Optimization Using Box-Behnken Design and In Vitro Evaluation.

Topical therapy of antifungals is primarily restricted due to the low innate transport of drugs through the thick multi-layered keratinized nail plate. The objective of this investigation was to develop a gel formulation, and to optimize and evaluate the transungual delivery of terbinafine using the constant voltage iontophoresis technique. Statistical analysis was performed using Box-Behnken design to optimize the transungual delivery of terbinafine by examining crucial variables namely concentration of polyethylene glycol, voltage, and duration of application (2-6 h). Optimization data in batches (F1-F17) demonstrated that chemical enhancer, applied voltage, and application time have influenced terbinafine nail delivery. Higher ex vivo permeation and drug accumulation into the nail tissue were noticed in the optimized batch (F8) when compared with other batches (F1-F17). A greater amount of terbinafine was released across the nails when the drug was accumulated by iontophoresis than the passive counterpart. A remarkably higher zone of inhibition was observed in nails with greater drug accumulation due to iontophoresis, as compared to the passive process. The results here demonstrate that the optimized formulation with low voltage iontophoresis could be a viable and alternative tool in the transungual delivery of terbinafine, which in turn could improve the success rate of topical nail therapy in onychomycosis.

Development of Ecofriendly Derivative Spectrophotometric Methods for the Simultaneous Quantitative Analysis of Remogliflozin and Vildagliptin from Formulation.

Three rapid, accurate, and ecofriendly processed spectrophotometric methods were validated for the concurrent quantification of remogliflozin (RGE) and vildagliptin (VGN) from formulations using water as dilution solvent. The three methods developed were based on the calculation of the peak height of the first derivative absorption spectra at zero-crossing points, the peak amplitude difference at selected wavelengths of the peak and valley of the ratio spectra, and the peak height of the ratio first derivative spectra. All three methods were validated adapting the ICH regulations. Both the analytes showed a worthy linearity in the concentration of 1 to 60 µg/mL and 2 to 90 µg/mL for VGN and RGE, respectively, with an exceptional regression coefficient (r2 ≥ 0.999). The developed methods demonstrated an excellent recovery (98.00% to 102%), a lower percent relative standard deviation, and a relative error (less than ±2%), confirming the specificity, precision, and accuracy of the proposed methods. In addition, validated spectrophotometric methods were commendably employed for the simultaneous determination of VGN and RGE from solutions prepared in the laboratory and the formulation. Hence, these methods can be utilized for the routine quality control study of the pharmaceutical preparations of VGN and RGE in pharmaceutical industries and laboratories. The ecofriendly nature of the anticipated spectrophotometric procedures was confirmed by the evaluation of the greenness profile by a semi-quantitative method and the quantitative and qualitative green analytical procedure index (GAPI) method.

Multivesicular Liposome: A Lipid-based Drug Delivery System for Efficient Drug Delivery.

The advancement of delivery tools for therapeutic agents has brought several novel formulations with increased drug loading, sustained release, targeted delivery, and prolonged efficacy. Amongst the several novel delivery approaches, multivesicular liposome has gained potential interest because this delivery system possesses the above advantages. In addition, this multivesicular liposomal delivery prevents degradation of the entrapped drug within the physiological environment while administered. The special structure of the vesicles allowed successful entrapment of hydrophobic and hydrophilic therapeutic agents, including proteins and peptides. Furthermore, this novel formulation could maintain the desired drug concentration in the plasma for a prolonged period, which helps to reduce the dosing frequencies, improve bioavailability, and safety. This tool could also provide stability of the formulation, and finally gaining patient compliance. Several multivesicular liposomes received approval for clinical research, while others are at different stages of laboratory research. In this review, we have focused on the preparation of multivesicular liposomes along with their application in different ailments for the improvement of the performance of the entrapped drug. Moreover, the challenges of delivering multivesicular vesicles have also been emphasized. Overall, it could be inferred that multivesicular liposomal delivery is a platform of advanced drug delivery with improved efficacy and safety.

Development of Mucoadhesive Buccal Film for Rizatriptan: In Vitro and In Vivo Evaluation.

The reduced therapeutic efficacy of rizatriptan in migraine treatment is primarily due to low oral bioavailability and extensive first pass metabolism. The purpose of this investigation was to optimize the thin mucoadhesive buccal film of rizatriptan and assess the practicability of its development as a potential substitute for conventional migraine treatment. Buccal films (FR1-FR10) were fabricated by a conventional solvent casting method utilizing a combination of polymers (Proloc, hydroxypropyl methylcellulose and Eudragit RS 100). Drug-loaded buccal films (F1-F4) were examined for mechanical, mucoadhesive, swelling and release characteristics. In vivo pharmacokinetics parameters of selected buccal film (F1) in rabbits were compared to oral administration. Films F1-F4 displayed optimal physicomechanical properties including mucoadhesive strength, which can prolong the buccal residence time. A biphasic, complete and higher drug release was seen in films F1 and F4, which followed Weibull model kinetics. The optimized film, F1, exhibited significantly higher (p < 0.005) rizatriptan buccal flux (71.94 ± 8.26 µg/cm2/h) with a short lag time. Film features suggested the drug particles were in an amorphous form, compatible with the polymers used and had an appropriate surface morphology suitable for buccal application. Pharmacokinetic data indicated a significantly higher rizatriptan plasma level (p < 0.005) and Cmax (p < 0.0001) upon buccal film application as compared to oral solution. The observed AUC0-12h (994.86 ± 95.79 ng.h/mL) in buccal treatment was two-fold higher (p < 0.0001) than the control, and the relative bioavailability judged was 245%. This investigation demonstrates the prospective of buccal films as a viable and alternative approach for effective rizatriptan delivery.

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies.

Solid lipid nanoparticles (SLNs) are being extensively exploited as topical ocular carrier systems to enhance the bioavailability of drugs. This study investigated the prospects of drug-loaded SLNs to increase the ocular permeation and improve the therapeutic potential of clarithromycin in topical ocular therapy. SLNs were formulated by high-speed stirring and the ultra-sonication method. Solubility studies were carried out to select stearic acid as lipid former, Tween 80 as surfactant, and Transcutol P as cosurfactant. Clarithromycin-loaded SLN were optimized by fractional factorial screening and 32 full factorial designs. Optimized SLNs (CL10) were evaluated for stability, morphology, permeation, irritation, and ocular pharmacokinetics in rabbits. Fractional factorial screening design signifies that the sonication time and amount of lipid affect the SLN formulation. A 32 full factorial design established that both factors had significant influences on particle size, percent entrapment efficiency, and percent drug loading of SLNs. The release profile of SLNs (CL9) showed ~80% drug release in 8 h and followed Weibull model kinetics. Optimized SLNs (CL10) showed significantly higher permeation (30.45 µg/cm2/h; p < 0.0001) as compared to control (solution). CL10 showed spherical shape and good stability and was found non-irritant for ocular administration. Pharmacokinetics data demonstrated significant improvement of clarithromycin bioavailability (p < 0.0001) from CL10, as evidenced by a 150% increase in Cmax (~1066 ng/mL) and a 2.8-fold improvement in AUC (5736 ng h/mL) (p < 0.0001) as compared to control solution (Cmax; 655 ng/mL and AUC; 2067 ng h/mL). In summary, the data observed here demonstrate the potential of developed SLNs to improve the ocular permeation and enhance the therapeutic potential of clarithromycin, and hence could be a viable drug delivery approach to treat endophthalmitis.

Experimental design, formulation and in vivo evaluation of a novel topical in situ gel system to treat ocular infections.

In situ gels have been extensively explored as ocular drug delivery system to enhance bioavailability and efficacy. The objective of present study was to design, formulate and evaluate ion-activated in situ gel to enhance the ocular penetration and therapeutic performance of moxifloxacin in ophthalmic delivery. A simplex lattice design was utilized to examine the effect of various factors on experimental outcomes of the in situ gel system. The influence of polymers (independent variables) such as gellan gum (X1), sodium alginate (X2), and HPMC (X3) on gel strength, adhesive force, viscosity and drug release after 10 h (Q10) were assessed. Selected formulation (MH7) was studied for ex vivo permeation, in vivo irritation and pharmacokinetics in rabbits. Data revealed that increase in concentration of polymers led to higher gel strength, adhesive force and viscosity, however, decreases the drug release. MH7 exhibited all physicochemical properties within acceptable limits and was stable for 6 months. Release profile of moxifloxacin from MH7 was comparable to the check point batches and followed Korsmeyer-Peppas matrix diffusion-controlled mechanism. Ocular irritation study signifies that selected formulation is safe and non-irritant for ophthalmic administration. In vivo pharmacokinetics data indicates significant improvement of moxifloxacin bioavailability (p < 0.0001) from MH7, as evidenced by higher Cmax (727 ± 56 ng/ml) and greater AUC (2881 ± 108 ng h/ml), when compared with commercial eye drops (Cmax; 503 ± 85 ng/ml and AUC; 978 ± 86 ng h/ml). In conclusion, developed in situ gel system (MH7) could offers a more effective and extended ophthalmic therapy of moxifloxacin in ocular infections when compared to conventional eye drops.

Development and Validation of Green UV Derivative Spectrophotometric Methods for Simultaneous Determination Metformin and Remogliflozin from Formulation: Evaluation of Greenness.

The recent trend in green analytical chemistry is the development of green analytical methods using environmentally friendly solvents. Therefore, three ecofriendly manipulated UV spectroscopic techniques have been validated for the concurrent quantification of newly approved remogliflozin etabonate (REM) and metformin HCl (MET) tablets using water as a solvent. The first method was established using first derivative absorption spectroscopic method by determining the peak amplitude at 233.0 nm for REM and 252.2 nm for MET, a zero crossing of one the component. The second and third methods were based on the peak amplitude difference and first-order derivative absorption of the ratio spectra developed by the manipulation of scanned UV spectra. REM and MET showed good linearity in the series of 1-20 µg ml-1 and 2.5-35 µg ml-1, respectively, by all three methods with an excellent correlation coefficient (r2 ≥ 0.998). Further, the proposed UV spectroscopic techniques were validated as per International Council for Harmonization guidelines. The methods showed good sensitivity, accuracy, and precision. Anticipated procedures were effectively utilized for the concurrent quantification of REM and MET in laboratory prepared mixtures and tablets. The high percent recovery with low standard deviation found for both analytes by all three methods confirms the accuracy and precision of the procedures. Finally, the greenness of the proposed spectroscopic methods, evaluated by semi-quantitative and quantitative methods, showed the eco-friendly nature of the methods. Furthermore, the proposed approaches were simple, accurate, sensitive, economic, and environmentally friendly and hence can be utilized for regular quality control of REM and MET formulation.

Mechanisms of Antidiabetic Activity of Methanolic Extract of Punica granatum Leaves in Nicotinamide/Streptozotocin-Induced Type 2 Diabetes in Rats.

The current study aimed to establish the mechanisms of antidiabetic activity of methanolic extract of Punica granatum leaves (MEPGL) in nicotinamide/streptozotocin-induced type 2 diabetes in rats. Phytochemical screening, HPLC analysis, and acute toxicity study of MEPGL were carried out. Various concentrations of MEPGL (100, 200, 400, and 600 mg/kg) were administered orally to diabetic rats for 45 days on a daily basis. The antidiabetic effect of MEPGL was examined by measuring blood glucose, plasma insulin, and glycated hemoglobin (HbA1c) levels, as well as with an oral glucose tolerance test. The antioxidant effect of MEPGL was determined by analyzing hepatic and renal antioxidant markers, namely superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation. The other biochemical markers alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea, and creatinine, as well as total cholesterol, triglycerides, and high-density lipoprotein (HDL) were also studied. Type 2 diabetes significantly altered these parameters, while oral administration of the MEPGL significantly ameliorated them. Moreover, the pancreatic histopathological changes were attenuated with MEPGL treatment. In a nutshell, oral MEPGL administration in diabetic rats showed antidiabetic activity due to its antioxidant activity, most probably due to the gallic acid, ellagic acid, and apigenin found in MEPGL.

The Beneficial Effect of Boswellic Acid on Bone Metabolism and Possible Mechanisms of Action in Experimental Osteoporosis.

Estrogen is instrumental in the pathological process of osteoporosis because a deficiency of this hormone increases the release of bone-resorbing cytokines. Acetyl-11-keto-ß-boswellic acid (AKBA), a constituent from Boswellia serrata, has an anti-inflammatory effect by inhibiting tumor necrosis factor-α (TNF-α) expression, which leads to a decline in receptor activator of nuclear factor-kappa B (NF-κB) ligand, and consequently, a reduction in osteoclast activity. Hence, AKBA may be beneficial against bone loss during osteoporosis. Therefore, the current study intended to evaluate the beneficial effects of AKBA in ovariectomy-induced osteoporosis and to investigate its mechanism of action. Sham-operation or ovariectomy female Sprague Dawley rats were used for evaluating the antiosteoporotic effect of AKBA in this study. AKBA (35 mg/kg, p.o.) and estradiol (0.05 mg/kg, i.m.) were administered for 42 days. At the end of the experiment, body and uterus weights, serum and urine calcium and phosphorus, serum alkaline phosphatase, and urinary creatinine levels, besides serum levels of NF-κB and TNF-α were determined. Weight, length, thickness, hardness, calcium content, as well as the bone mineral density of femur bone and lumbar vertebra were measured. A histopathological examination was also carried out. AKBA ameliorated all tested parameters and restored a normal histological structure. Thus, AKBA showed good antiosteoporotic activity, which may be mediated through its suppression of the NF-κB-induced TNF-α signaling pathway.

Mucoadhesive buccal film of almotriptan improved therapeutic delivery in rabbit model.

Administration of almotriptan as an oral therapy is largely limited because of poor aqueous solubility and rather low bioavailability. The aim of present investigation was to formulate oral mucoadhesive film of almotriptan to improve the drug delivery and desired therapeutic effects. Placebo films (F1-F8) were prepared by varying the concentrations of Proloc 15 (7.5-15% w/v) and Eudragit RL 100/RS 100 (15-30% w/v) polymers. Physicomechanical and pharmaceutical characteristics of drug loaded films (FA1-FA4) were examined. Selected FA4 film was evaluated in vivo by assessing the pharmacokinetic profile and compared with oral therapy in rabbits. FA1-FA4 films exhibited excellent physicomechanical properties and rapid hydration. A biphasic and considerably greater drug release (p < 0.05) was observed in FA3 and FA4 films contain higher amount of hydrophilic polymer. The rate of permeation of almotriptan was found to be significantly higher in FA4 than FA3 film (p < 0.005). Fourier transform infrared spectral scan indicates no incompatibility exists between the drug and polymers used. Differential scanning calorimetry thermogram represents the evidence of almotriptan amorphization and molecular dispersion of it in the film. Scanning electron microscopy images shows that FA4 possess good morphological features and hence suitable for use in the buccal application. In vivo data demonstrated rapid and efficient absorption (p < 0.005) of almotriptan with greater AUC0-12 (>2 folds, p < 0.0001) by FA4 film as compared to oral (control). In general, the data established the potential of FA4 film to improve the therapeutic delivery of almotriptan and offers a promising option in migraine therapy.

Mucoadhesive Particles: A Novel, Prolonged-Release Nanocarrier of Sitagliptin for the Treatment of Diabetics.

Sitagliptin (MK-0431) is a widely and commonly used oral hypoglycemic drug in the treatment of type 2 diabetes mellitus; patients typically take higher doses of this drug (50 mg, twice daily). One drawback is that only 38% of the drug is bound reversibly to plasma proteins and 79% is excreted in urine without being metabolized. To overcome this issue, there is a need for a better drug-delivery method to improve its efficacy in patients. It has been found that in existing formulations, the drug content is 72.5% ± 5% and the percentage yield is 84.9% ± 3%. In this study, sitagliptin nanoparticles (sizes ranging from 210 to 618 nm) were developed. The bioadhesion properties of the nanoparticles, as well as the swelling of the nanoparticles on the mucus membrane aided in sustained drug release. The pattern of drug release was in accordance with the Peppas model. Fourier-transform infrared (FTIR) spectroscopy demonstrated that there were no significant interactions between sitagliptin and chitosan. Differential scanning calorimetry (DSC) results showed an absence of drug peaks due to the fact that the drug was present in an amorphous state. Mucoadhesive nanoparticles were formulated using sitagliptin and were effective for about 12 hours in the gastrointestinal tract. When compared to conventional sitagliptin administration, use of a nanoparticle delivery system demonstrated greater benefits for use in oral delivery applications. This is the first time that a drug-delivery method based on the mucoadhesive properties of nanoparticles could prolong the drug-release time of sitagliptin.

Development of Asialoglycoprotein Receptor-Targeted Nanoparticles for Selective Delivery of Gemcitabine to Hepatocellular Carcinoma.

Selective targeting of anticancer drugs to the tumor site is beneficial in the pharmacotherapy of hepatocellular carcinoma (HCC). This study evaluated the prospective of galactosylated chitosan nanoparticles as a liver-specific carrier to improve the therapeutic efficacy of gemcitabine in HCC by targeting asialoglycoprotein receptors expressed on hepatocytes. Nanoparticles were formulated (G1-G5) by an ionic gelation method and evaluated for various physicochemical characteristics. Targeting efficacy of formulation G4 was evaluated in rats. Physicochemical characteristics exhibited by nanoparticles were optimal for administering and targeting gemcitabine effectively to the liver. The biphasic release behavior observed with G4 can provide higher drug concentration and extend the pharmacotherapy in the liver target site. Rapid plasma clearance of gemcitabine (70% in 30 min) from G4 was noticed in rats with HCC as compared to pure drug (p < 0.05). Higher uptake of gemcitabine predominantly by HCC (64% of administered dose; p < 0.0001) demonstrated excellent liver targeting by G4, while mitigating systemic toxicity. Morphological, biochemical, and histopathological examination as well as blood levels of the tumor marker, alpha-fetoprotein, in rats confirmed the curative effect of G4. In conclusion, this study demonstrated site-specific delivery and enhanced in vivo anti-HCC efficacy of gemcitabine by G4, which could function as promising carrier in hepatoma.

HPMC- and PLGA-Based Nanoparticles for the Mucoadhesive Delivery of Sitagliptin: Optimization and In Vivo Evaluation in Rats.

Mucoadhesive nanoparticles represent a potential drug delivery strategy to enhance the therapeutic efficacy in oral therapy. This study assessed the prospective of developing HPMC- and PLGA-based nanoparticles using a nanospray drier as a mucoadhesive extended release drug delivery system for sitagliptin and evaluated their potential in an animal model. Nanoparticles were prepared using a Buchi® B-90 nanospray drier. Optimization of particle size was performed using response surface methodology by examining the influence of spray-drying process variables (inlet temperature, feed flow, and polymer concentration) on the particle size. The prepared nanoparticles were characterized for various physicochemical characteristics (yield, drug content, morphology, particle size, thermal, and crystallographic properties) and assessed for drug release, stability, and mucoadhesive efficacy by ex vivo and in vivo studies in rats. A linear model was suggested by the design of the experiments to be the best fit for the generated design and values. The yield was 77 ± 4%, and the drug content was 90.5 ± 3.5%. Prepared nanoparticles showed an average particle size of 448.8 nm, with a narrow particle size distribution, and were wrinkled. Thermal and crystallographic characteristics showed that the drug present in the nanoparticles is in amorphous dispersion. Nanoparticles exhibited a biphasic drug release with an initial rapid release (24.9 ± 2.7% at 30 min) and a prolonged release (98.9 ± 1.8% up to 12 h). The ex vivo mucoadhesive studies confirmed the adherence of nanoparticles in stomach mucosa for a long period. Histopathological assessment showed that the formulation is safe for oral drug delivery. Nanoparticles showed a significantly higher (p < 0.05) amount of sitagliptin retention in the GIT (gastrointestinal tract) as compared to control. The data observed in this study indicate that the prepared mucoadhesive nanoparticles can be an effective alternative delivery system for the oral therapy of sitagliptin.

Graphene-based hybrid nanoparticle of doxorubicin for cancer chemotherapy.

BACKGROUND: Prostate cancer (PC) has the highest prevalence in men and accounts for a high rate of neoplasia-related death. Doxorubicin (DOX) is one of the most widely used anti-neoplastic drugs for prostate cancer among others. However, it has low specificity and many side effects and affects normal cells. More recently, there have been newly developed drug delivery tools which are graphene or graphene-based, used to increase the specificity of the delivered drug molecules. The graphene derivatives possess both π-π stacking and increased hydrophobicity, factors that increase the likelihood of drug delivery. Despite this, the hydrophilicity of graphene remains problematic, as it induced problems with stability. For this reason, the use of a chitosan coating remains one way to modify the surface features of graphene. METHOD: In this investigation, a hybrid nanoparticle that consisted of a DOX-loaded reduced graphene oxide that is stabilized with chitosan (rGOD-HNP) was developed. RESULT: The newly developed rGOD-HNP demonstrated high biocompatibility and efficiency in entrapping DOX (~65%) and releasing it in a controlled manner (~50% release in 48 h). Furthermore, it was also demonstrated that rGOD-HNP can intracellularly deliver DOX and more specifically in PC-3 prostate cancer cells. CONCLUSION: This delivery tool offers a feasible and viable method to deliver DOX photo-thermally in the treatment of prostate cancer.

Gellan Gum-Based Hydrogel for the Transdermal Delivery of Nebivolol: Optimization and Evaluation.

Poor solubility and appreciable first-pass metabolism have limited the oral bioavailability of nebivolol. The objective of the current investigation was to design, formulate, and optimize a hydrogel-based transdermal system for nebivolol using factorial design and compare its pharmacokinetics with oral suspension. Hydrogel formulations (F1-F8) were prepared by varying the amounts of gellan gum, carbopol, and polyethylene glycol. A 23 full factorial design was used to assess the effect of independent variables such as gellan gum, carbopol, and polyethylene glycol 400 on dependent variables like viscosity, in vitro release, and ex vivo permeation after 2 h at two levels. Optimized gel (F7), containing nebivolol hydrochloride (75 mg), gellan gum (300 mg), carbopol (150 mg), polyethylene glycol 400 (20 µl), tween 80 (1 ml), ethanol (10 ml), and water (up to 30 ml) was selected and evaluated in albino rats. The physicochemical properties of F7 (pH: 7.1 ± 0.15, viscosity: 8943 ± 116 centipoise, drug content: 98.81% ± 2.16%) seem ideal for transdermal application. It was noticed that the concentration of carbopol has a more significant role than gellan gum in gel viscosity. A biphasic release pattern was exhibited by gels, and the release rate was mainly influenced by the concentration of gellan gum. Greater transdermal flux (30.86 ± 4.08 µg/cm2/h) was observed in F7 as compared with other prepared gels. Noticeable enhancement in AUC0-α value (986.52 ± 382.63 ng.h/ml; p < 0.01) of transdermal therapy (~2-fold higher compared with oral administration) established the potential of F7 to improve the rate and extent of nebivolol delivery. The overall results demonstrated here signify that F7 could be a feasible alternative to oral therapy of nebivolol.

Effective Therapeutic Delivery and Bioavailability Enhancement of Pioglitazone Using Drug in Adhesive Transdermal Patch.

The administration of pioglitazone as an oral therapy is restricted due to various challenges. The aim of the current investigation was to evaluate the suitability of pioglitazone in adhesive transdermal patch as an alternative delivery system, in order to improve therapeutic delivery. Drug in adhesive pioglitazone (2% w/w) transdermal patch were optimized for drug release, suitable adhesive, and skin permeation enhancer. The selected patch was examined for drug-loading capacity and the patch with greater pioglitazone (6% w/w) was evaluated in rat models. The release of pioglitazone was influenced by the tested adhesive and was shown to be significantly higher (p < 0.001) with patch, prepared using Duro-Tak 87-2516. The ex vivo permeation results substantiate the release data as a greater transdermal flux (15.67 ± 2.35 µg/cm2/h) was demonstrated in patch fabricated with Duro-Tak 87-2516. Skin penetration enhancers promoted the ex vivo transdermal delivery of pioglitazone, and was ~2 folds (p < 0.0001) higher with propylene glycol, as compared to patch without enhancer. The maximum solubility of pioglitazone in Duro-Tak 87-2516 was found to be 6% w/w. Increasing the drug content in patch enhanced the transdermal flux and was highest when the pioglitazone level was 6% w/w (72.68 ± 5.76 µg/cm2/h). In vivo pharmacokinetic data demonstrate that the AUC0-α in transdermal application (13,506.51 ± 1649.92 ng·h/mL) was ~2 times higher (p < 0.0001) as compared to oral dosage form. In conclusion, the promising results observed here signifies that developed patch could be a viable alternative for oral therapy of pioglitazone.

Immobilization studies of Candida Antarctica lipase B on gallic acid resin-grafted magnetic iron oxide nanoparticles.

Purpose: Here, we present the successful preparation of a highly efficient gallic acid resin grafted with magnetic nanoparticles (MNPs) and containing a branched brush polymeric shell. Methods: Using a convenient co-precipitation method, we prepared Fe3O4 nanoparticles stabilized by citric acid. These nanoparticles underwent further silica modification and amino functionalization followed by gallic acid functionalization on their surface. Under alkaline conditions, we used a condensation reaction that combined formaldehyde and gallic, to graft the gallic acid-formaldehyde resin on the surface. We then evaluated the polymer-grafted MNPs to assay the Candida Antarctica B lipase(Cal-B) immobilization via physical adsorption. Conclusion: Furthermore, during optimization of parameters that defined conditions of immobilization, we found that the optimum immobilization was achieved in 15 mins. Also, optimal immobilization temperature and pH were 38ºC and 7.5, respectively. In addition, the reusability study of immobilized lipase polymer-grafted MNPs was done by isolating the MNPs from the reaction medium using magnetic separation, which showed that grafted MNPs reached 5 cycles with 91% activity retention.