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Three new cardenolides (3, 9 and 10), along with eight known ones, were isolated from the latex of Calotropis procera. The structural determination was accomplished by the 1D- and 2D-NMR spectra as well as HRESIMS analysis. The growth inhibitory activity of the latex and its sub-fractions as well as isolated compounds was evaluated against human A549 and Hela cell lines. The results exhibited that latex had strong growth inhibitory activity with IC50s of (3.37 lM, A-549) and (6.45 lM, Hela). Among the four extracts (hexane, chloroform, ethyl acetate and aqueous), chloroform extract displayed the highest potential cytotoxic activity, with IC50s of (0.985 lM, A-549) and (1.471 lM, Hela). All the isolated compounds displayed various degrees of cytotoxic activity and the highest activity was observed by calactin (1) with IC50s values of (0.036 lM, A-549) and (0.083 lM, Hela). None of these isolated compounds exhibited good antimicrobial activity evaluated by determination of their MICs using the broth microdilution method against various infectious pathogens. The structure–activity relationships for cytotoxic activity were also discussed.

Purpose: To develop a safe, lipid-based non-viral gene delivery system that achieves high transfection efficiency in the presence of serum proteins. Methods: Polyplexes with the pAcGFP1-C1 plasmid were formed in phosphate buffered saline, pH 7.4 (PBS) using the novel poly[N-(2-hydroxypropyl)methacrylamide]-poly(N,N-dimethylaminoethylmethacrylate) diblock copolymer (pHPMA-b-pDMAEMA) at N/P=4. Cationic-Liposomes were prepared from a dried lipid film comprised of equimolar 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOPE). Lipopolyplexes were fabricated at lipid/DNA weight ratios up to 40. Particle size distribution and zeta potential of lipopolyplexes were determined by dynamic light scattering. HeLa cells viability in the presence and absence of lipopolyplexes was quantified using the CellTiter-Glo® luminescent assay. HeLa cell transfection efficiency in the presence and absence of FBS was visually assessed by confocal microscopy and quantitatively compared to the TurboFect™ control. Results: pHPMA-b-pDMAEMA exhibited a high condensation capacity of 1 µg of pDNA per 0.513 μg of polymer (N/P=1). Lipid-coating of polyplexes at lipid/DNA weight ratios up to 40 resulted in particle sizes +25 mV. Exposure to FBS significantly increased mean particle size to >300 nm, reduced zeta potential to -10 mV, and augmented polydispersity. Lipid coating of polyplexes only decreased HeLa cell viability at lipid/DNA ratios >20. HeLa transfection with lipopolyplexes was most effective at lipid/DNA = 20 and was significantly greater in the presence of FBS than measured for lipid-free polyplexes. Conclusion: Lipid coating of pHPMA-b-pDMAEMA/DNA polyplexes with an equimolar DOTAP/DOPE mixture at a lipid/DNA ratio = 20 effectively enhances in vitro transfection efficiency of HeLa cells in the presence of serum proteins.

Purpose: To develop a safe, lipid-based non-viral gene delivery system that achieves high transfection efficiency in the presence of serum proteins. Methods: Polyplexes with the pAcGFP1-C1 plasmid were formed in phosphate buffered saline, pH 7.4 (PBS) using the novel poly[N-(2-hydroxypropyl)methacrylamide]-poly(N,N-dimethylaminoethylmethacrylate) diblock copolymer (pHPMA-b-pDMAEMA) at N/P=4. Cationic-Liposomes were prepared from a dried lipid film comprised of equimolar 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOPE). Lipopolyplexes were fabricated at lipid/DNA weight ratios up to 40. Particle size distribution and zeta potential of lipopolyplexes were determined by dynamic light scattering. HeLa cells viability in the presence and absence of lipopolyplexes was quantified using the CellTiter-Glo® luminescent assay. HeLa cell transfection efficiency in the presence and absence of FBS was visually assessed by confocal microscopy and quantitatively compared to the TurboFect™ control. Results: pHPMA-b-pDMAEMA exhibited a high condensation capacity of 1 µg of pDNA per 0.513 μg of polymer (N/P=1). Lipid-coating of polyplexes at lipid/DNA weight ratios up to 40 resulted in particle sizes +25 mV. Exposure to FBS significantly increased mean particle size to >300 nm, reduced zeta potential to -10 mV, and augmented polydispersity. Lipid coating of polyplexes only decreased HeLa cell viability at lipid/DNA ratios >20. HeLa transfection with lipopolyplexes was most effective at lipid/DNA = 20 and was significantly greater in the presence of FBS than measured for lipid-free polyplexes. Conclusion: Lipid coating of pHPMA-b-pDMAEMA/DNA polyplexes with an equimolar DOTAP/DOPE mixture at a lipid/DNA ratio = 20 effectively enhances in vitro transfection efficiency of HeLa cells in the presence of serum proteins.

Purpose: To develop a safe, lipid-based non-viral gene delivery system that achieves high transfection efficiency in the presence of serum proteins. Methods: Polyplexes with the pAcGFP1-C1 plasmid were formed in phosphate buffered saline, pH 7.4 (PBS) using the novel poly[N-(2-hydroxypropyl)methacrylamide]-poly(N,N-dimethylaminoethylmethacrylate) diblock copolymer (pHPMA-b-pDMAEMA) at N/P=4. Cationic-Liposomes were prepared from a dried lipid film comprised of equimolar 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOPE). Lipopolyplexes were fabricated at lipid/DNA weight ratios up to 40. Particle size distribution and zeta potential of lipopolyplexes were determined by dynamic light scattering. HeLa cells viability in the presence and absence of lipopolyplexes was quantified using the CellTiter-Glo® luminescent assay. HeLa cell transfection efficiency in the presence and absence of FBS was visually assessed by confocal microscopy and quantitatively compared to the TurboFect™ control. Results: pHPMA-b-pDMAEMA exhibited a high condensation capacity of 1 µg of pDNA per 0.513 μg of polymer (N/P=1). Lipid-coating of polyplexes at lipid/DNA weight ratios up to 40 resulted in particle sizes +25 mV. Exposure to FBS significantly increased mean particle size to >300 nm, reduced zeta potential to -10 mV, and augmented polydispersity. Lipid coating of polyplexes only decreased HeLa cell viability at lipid/DNA ratios >20. HeLa transfection with lipopolyplexes was most effective at lipid/DNA = 20 and was significantly greater in the presence of FBS than measured for lipid-free polyplexes. Conclusion: Lipid coating of pHPMA-b-pDMAEMA/DNA polyplexes with an equimolar DOTAP/DOPE mixture at a lipid/DNA ratio = 20 effectively enhances in vitro transfection efficiency of HeLa cells in the presence of serum proteins.

Purpose: To develop a safe, lipid-based non-viral gene delivery system that achieves high transfection efficiency in the presence of serum proteins. Methods: Polyplexes with the pAcGFP1-C1 plasmid were formed in phosphate buffered saline, pH 7.4 (PBS) using the novel poly[N-(2-hydroxypropyl)methacrylamide]-poly(N,N-dimethylaminoethylmethacrylate) diblock copolymer (pHPMA-b-pDMAEMA) at N/P=4. Cationic-Liposomes were prepared from a dried lipid film comprised of equimolar 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOPE). Lipopolyplexes were fabricated at lipid/DNA weight ratios up to 40. Particle size distribution and zeta potential of lipopolyplexes were determined by dynamic light scattering. HeLa cells viability in the presence and absence of lipopolyplexes was quantified using the CellTiter-Glo® luminescent assay. HeLa cell transfection efficiency in the presence and absence of FBS was visually assessed by confocal microscopy and quantitatively compared to the TurboFect™ control. Results: pHPMA-b-pDMAEMA exhibited a high condensation capacity of 1 µg of pDNA per 0.513 μg of polymer (N/P=1). Lipid-coating of polyplexes at lipid/DNA weight ratios up to 40 resulted in particle sizes +25 mV. Exposure to FBS significantly increased mean particle size to >300 nm, reduced zeta potential to -10 mV, and augmented polydispersity. Lipid coating of polyplexes only decreased HeLa cell viability at lipid/DNA ratios >20. HeLa transfection with lipopolyplexes was most effective at lipid/DNA = 20 and was significantly greater in the presence of FBS than measured for lipid-free polyplexes. Conclusion: Lipid coating of pHPMA-b-pDMAEMA/DNA polyplexes with an equimolar DOTAP/DOPE mixture at a lipid/DNA ratio = 20 effectively enhances in vitro transfection efficiency of HeLa cells in the presence of serum proteins.

In view of the wide clinical use of theophylline, its narrow therapeutic index, repeated daily dosing and gastrointestinal side effects, sustained-release microcapsules of theophylline were prepared by a modified emulsion-solvent evaporation –non solvent addition technique. Two different polymers, namely, cellulose acetate butyrate (CAB) and ethyl cellulose (EC) were utilized at different polymer to drug ratios (2:1, 1:1 and 1:2). The microcapsules were evaluated in vitro for total recovery (yield %), microcapsule size (sieve analysis), surface morphology by scanning electron microscopy (SEM), drug loading (encapsulation efficiency) and drug release characteristics in simulated GIT fluids (pH 1.2 and 6.8). Results obtained revealed that spherical, free flowing microcapsules with smooth surfaces were successfully prepared with the two polymers. The percentages drug loading (encapsulation efficiency) were more than 95% for the two polymers at different polymer to drug ratios, indicating efficiency of the method. The drug release was affected by the type of polymer, polymer to drug ratios, microcapsule size and pH of the dissolution medium. The release of theophylline from CAB was slower than EC microcapsules. The release of theophylline from the microcapsules increased with decreasing microcapsules size. The release of theophylline from all the prepared microcapsules was markedly retarded as compared to commercial theophylline marketed product (Theo SR 100 Capsules). The release of theophylline from the prepared can be described by Zero-order release kinetic. These data clearly indicate ability of the prepared microcapsules to control and sustain the release of theophylline which is important for subsequent sustained absorption rate from GIT that can results in decreasing or eliminating gastrointestinal side effects as well as maintaining constant blood level for such drug with narrow therapeutics index, theophylline.