The present investigation explores the use of folic acid (FA)-conjugated chitosan (CS)-functionalized poly (d,l-lactide-co-glycolide) (PLGA) nanocarriers for treatment of prostate cancer. A folic ...acid–chitosan conjugate was prepared to coat nanoparticles (NPs). Bicalutamide (BCL)-loaded nanoparticles were prepared using the nanoprecipitation method under a Box–Behnken-RSM design and characterized through MPS, PDI, ZP, SEM, PXRD, DSC, in vitro release, in vitro cytotoxicity, protein adsorption, hemolysis and stability studies. The MPS, ZP, %EE and %DL of the BCL-loaded FA conjugated CS-functionalized PLGA NPs (CPN) formulation were 206.9nm, +21.7mV, 87.11% and 9.37%, respectively. The drug release of the optimized BCL-loaded CPN was found to be 101.27±1.61% at 120h. The IC50 value of the optimized coated batch was <80μg/ml, as compared with a value of >80μg/ml for the BCL suspension, determined through a cytotoxicity assay. DSC, FTIR and PXRD studies confirmed sufficient drug entrapment along with amorphous behavior of the drug in optimized formulations. Hemolytic studies revealed that the BCL-loaded CPN was stable in blood. The stability data revealed that the CPN was stable in a phosphate buffer (pH7.4). The CPN was also stable in short term studies carried out according to ICH Q1A (R2) guidelines. It can be concluded from all these studies that FA conjugated CS-functionalized PLGA NPs are safe and stable, so may useful in cancer therapy.
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•Box Behnkendesign is reported for PLGA nanoparticle optimization.•Nanoparticle surface is modified using FA–CS conjugation.•Bicalutamide is used as a model drug for treatment of prostate cancer.•Cell viability using DU-145 cells is performed using BCL-loaded UPN and CPN.•CPN is found to be more cytotoxic towards cancer cell line as compared to UPN and pure BCL.•CPN is found to be stable as compare to UPN for the treatment of prostate cancer.
Paclitaxel (PTX) is an essential anticancer drug from the biopharmaceutical classification system (BCS) class IV. Unfortunately, PTX has some drawbacks including low solubility, cell toxicity, ...adverse cell reaction, etc. Therefore, folic acid (FA) tailored carboxymethyl-dextran (CMD), and bovine serum albumin (BSA) mediated nanoconjugates of paclitaxel (PTX) (FA-CMD-BSA-PTX) were designed. At first, esterification reaction between FA and CMD resulted in FA-CMD conjugate whereas FA-CMD-BSA conjugate was synthesized via the Maillard reaction. Finally, FA-CMD-BSA conjugates of PTX were achieved via hydrophobic interaction and gelation of BSA. Herein, heating offers the gelation of BSA that furnishes the cross-linking wherein PTX gets fixed inside BSA. Thermogram of FA-CMD-BSA-PTX showed the absence of PTX peak that concluding PTX has been molecularly dispersed in polymer matrix and entrapment inside polymeric conjugate. As an effect, surface decorated FA-CMD-BSA-PTX showed low hemolytic toxicity over free PTX. Cytotoxicity assay on A549 human lung cancer cells shows cell viability decreased from 60 % to 10 % with increasing concentration from 1 to 5 μg/mL. In conclusion, CMD facilitates the circulation time of PTX and BSA acts as a carrier to target tumor locations effectively. The nano-conjugate formulation significantly reduces toxicity and can be used for the treatment of lung cancer.
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•Non-small cell lung cancer accounts for 85 % of lung cancer.•Folic acid-tailored carboxymethyl-dextran and bovine serum albumin-based nanoconjugates of paclitaxel were designed.•Folic acid on the nanoconjugates surface enables the conjugate to target folate receptor-over expressed in tumor.•Anticipated folic acid-tailored paclitaxel nanoconjugates improved the anticancer activity in human lung cancer cells.•The design of surface-tailored carboxymethyl dextran-protein-based nanoconjugates will provide a new alternative for paclitaxel delivery.
The aim of this work was to evaluate the in vitro performance of nebulized nanosuspension formulation when nebulized using ultrasonic nebulizer. The present investigation deals with successful ...formulation of Beclomethasone dipropionate loaded HPMCP nanospheres prepared by solvent evaporation technique using PEG 400 as a stabilizer. Beclomethasone dipropionate is a water insoluble drug molecule was encapsulated in HPMCP nanospheres to have pH dependent solubility at basic pH for targeted drug delivery in lung and studied for in vitro cytotoxicity and immediate release capability. The synthesized nanospheres were characterized through drug excipient compatibility, surface topography; mean particle size , zeta potential, PDI, entrapment efficiency and drug loading, in vitro diffusion, aerodynamic, in vitro cytotoxicity and stability studies. The mean particle size and PDI of the optimized batch (F1) had 197.6±0.40 nm and 0.324 ±0.35, respectively. The % entrapment efficiency and % drug loading was found to be 86.56±1.32 and 8.30±0.27, respectively. The optimized batch F1 showed % cumulative drug release 94.77±0.24 at 1 h. The formulation showed cell viability up to 91.28%. It can be concluded that, Beclomethasone dipropionate loaded HPMCP nanospheres was found to be safe, stable with significant increase in solubility and bypass the liver.
Drug delivery to the eye is challenging due to immediate drainage of eyedrops from the eye, low volume of the cul-de-sac (10–20 µl), the sensitivity of the corneal layer, physicochemical properties ...of a drug, biological barriers, need for repeated instillation, which finds difficulties for patients. Furthermore, it is difficult to carry drugs across the blood–retinal barrier, and across the cornea when administered systemically and topically, respectively, due to the limited absorption rate at a targeted site. Owing to the static and dynamic constraints associated with the eyes, the permeation of therapeutics to the back of the eye is limited. The use of drug delivery systems that can remain in contact with the ocular surface for a prolonged duration can greatly reduce the frequency of dosing, whereas drug delivery systems that cross ocular barriers may provide greater efficacy of administered drugs to inaccessible ocular tissues. In this review, we explored barrier properties of the ocular tissues, as well as the various drug transport mechanisms in the eye to design an effective strategy. This followed a discussion on the recent strategies to enhance the ocular distribution of therapeutics and have a future for translational nanomedicine.
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Bicalutamide (BCM) is an anti-androgen drug used to treat prostate cancer. In this study, nanostructured lipid carriers (NLCs) were chosen as a carrier for delivery of BCM using Box-Behnken (BB) ...design for optimizing various quality attributes such as particle size and entrapment efficiency which is very critical for efficient drug delivery and high therapeutic efficacy. Stability of formulated NLCs was assessed with respect to storage stability, pH stability, hemolysis, protein stability, serum protein stability and accelerated stability. Hot high-pressure homogenizer was utilized for formulation of BCM-loaded NLCs. In BB response surface methodology, total lipid, % liquid lipid and % soya lecithin was selected as independent variable and particle size and %EE as dependent variables. Scanning electron microscopy (SEM) was done for morphological study of NLCs. Differential scanning calorimeter and X-ray diffraction study were used to study crystalline and amorphous behavior. Analysis of design space showed that process was robust with the particle size less than 200 nm and EE up to 78%. Results of stability studies showed stability of carrier in various storage conditions and in different pH condition. From all the above study, it can be concluded that NLCs may be suitable carrier for the delivery of BCM with respect to stability and quality attributes.
This study investigates the extrusion-spheronization performance of some mixtures of co-processed κ-carrageenan and pectin (as excipient), and sodium starch glycolate (as superdisintegrant). ...Attention is focused with an objective to improve the mechanical stability and the dissolution rate of poorly soluble domperidone (as a model drug). Initially, co-processed κ-carrageenan-pectin excipient is prepared with different ratios of κ-carrageenan and pectin. Different marketed brands of κ-carrageenan (Gelcarin, Aquagel and Eugel) were employed and dried by solvent evaporation method. Further characterization was carried out by SEM, XRD and FTIR analysis. Pellets were prepared using extrusion-spheronization technique. Pellets were evaluated for flow properties, particle size, sphericity, tensile strength, friability, disintegration time and in-vitro drug release studies. Solid-state characterization of pellets was also done by FTIR, DSC and SEM analysis. The mechanical stability and dissolution rate of prepared pellets were found to be dependent on the concentration of pectin and type of κ-carrageenan employed in the fabrication of pellets. The pellets made with a high proportion of Eugel showed a very high dissolution rate of domperidone and undergo rapid disintegration validating co-processed k-carrageenan-pectin as a promising pelletizing aid for immediate-release pharmaceutical formulations.
This study investigates the extrusion-spheronization performance of some mixtures of co-processed κ-carrageenan and pectin (as excipient), and sodium starch glycolate (as superdisintegrant). ...Attention is focused with an objective to improve the mechanical stability and the dissolution rate of poorly soluble domperidone (as a model drug). Initially, co-processed κ-carrageenan-pectin excipient is prepared with different ratios of κ-carrageenan and pectin. Different marketed brands of κ-carrageenan (Gelcarin, Aquagel and Eugel) were employed and dried by solvent evaporation method. Further characterization was carried out by SEM, XRD and FTIR analysis. Pellets were prepared using extrusion-spheronization technique. Pellets were evaluated for flow properties, particle size, sphericity, tensile strength, friability, disintegration time and in-vitro drug release studies. Solid-state characterization of pellets was also done by FTIR, DSC and SEM analysis. The mechanical stability and dissolution rate of prepared pellets were found to be dependent on the concentration of pectin and type of κ-carrageenan employed in the fabrication of pellets. The pellets made with a high proportion of Eugel showed a very high dissolution rate of domperidone and undergo rapid disintegration validating co-processed k-carrageenan-pectin as a promising pelletizing aid for immediate-release pharmaceutical formulations.
