Design, In Silico, and In vitro Evaluation of Polymer-Based Drug Conjugates Incorporated with Derivative of Cinnamic Acid, Zidovudine, and 4-Aminosalicylic Acid against Pseudo-HIV-1.

BACKGROUND: The incorporation of anti-HIV drugs into polymer to form polymer-drug conjugates has been reported to result in improved therapeutic activity. Zidovudine, an anti-HIV drug, was explored alone and in combination with known drug molecules using polyamidoaminebased carriers. OBJECTIVE: Polymer-drug conjugates incorporated with zidovudine, cinnamic acid, and 4-aminosalicylic acid were prepared and evaluated for their potential efficacy in vitro against pseudo- HIV-1. METHODS: Aqueous Michael addition polymerization reaction was employed to prepare the conjugates. The conjugates were incorporated with zidovudine, cinnamic acid, and 4-aminosalicylic acid. They were characterized by SEM/EDX, XRD, FTIR, NMR, LC-MS, particle size analysis, in vitro analysis, computational studies, and in silico toxicity predictions. RESULTS: The conjugates displayed spherically shaped morphology. The in vitro findings showed that polymer-drug conjugates, T15 and T16, with a single drug were effective against pseudo- HIV-1 at high concentrations of 111.11 and 333.33 µg/mL, respectively. The molecular docking studies confirmed the in vitro results. The Swiss ADME, ProTox-II, and GUSAR (General Unrestricted Structure-Activity Relationships) revealed that these compounds are promising antiviral compounds. CONCLUSION: The prepared polymer-drug conjugates with a single drug showed promising effects against the Pseudo-HIV-1, and the conjugates displayed features that make them potential anti- HIV therapeutics that require further studies.

Dissolvable sodium alginate-based antibacterial wound dressing patches: Design, characterization, and in vitro biological studies.

The treatment of infected wounds in patients with highly sensitive skin is challenging. Some of the available wound dressings cause further skin tear and bleeding upon removal thereby hindering the healing process. In this study, dissolvable antibacterial wound dressing patches loaded with cephalexin monohydrate were prepared from different amounts of sodium alginate (SA) and carboxymethyl cellulose (CMC) by the solvent casting evaporation technique. The patches displayed good tensile strength (3.83-13.83 MPa), appropriate thickness (0.09 to 0.31 mm) and good flexibility (74-98 %) suitable for the skin. The patches displayed good biodegradability and low moisture uptake suitable to prevent microbial invasion on the wound dressings upon storage. The release profile of the drug from the patches was sustained in the range of 47-80 % for 48 h, revealing their capability to inhibit bacterial infection. The biological assay showed that the patches did not induce cytotoxic effects on HaCaT cells, revealing good biocompatibility. The antimicrobial effect of the patches on the different strains of bacteria used in the study was significant. The cell migration (66.7-74.3 %) to the scratched gap was promising revealing the patches' capability to promote wound closure. The results obtained show that the wound dressings are potential materials for the treatment of infected wounds.

Alginate-gum acacia based sponges as potential wound dressings for exuding and bleeding wounds.

The improper management of wound exudates can expose the wound to bacterial invasion, skin maceration etc. thereby resulting in prolonged wound healing. Biopolymers are characterized by hydrophilic functional groups which when employed for the development of wound dressings promote the wound dressings capability to absorb a high amount of wound exudates. Alginate-gum acacia sponges were prepared from a combination of biopolymers such as sodium alginate and gum acacia in varying amounts with carbopol via crosslinking with 1 and 2% CaCl2. The prepared sponges were loaded with a combination of ampicillin and norfloxacin. In vitro antibacterial analysis revealed that the antibacterial activity of the loaded antibiotics was retained and the sponges were effective against gram-positive and gram-negative bacteria. The sponges displayed rapid and high absorption capability in the range of 1022-2419% at pH 5.5 simulating wound exudates, and 2268-5042% at pH 7.4 simulating blood within a period of 1-3 h. Furthermore, the whole blood clotting studies further revealed low absorbance values when compared to the control revealing the good clotting capability of the sponges. The unique features of the sponges revealed their potential application for the management of infected, high exuding and bleeding wounds.

Synthesis, characterization and the release kinetics of antiproliferative agents from polyamidoamine conjugates.

Polyamidoamine conjugates containing curcumin and bisphosphonate were synthesized via a one-pot aqueous phase Michael addition reaction. In the design of the conjugate, bisphosphonate formed an integral part of the polymer carrier backbone. Curcumin was incorporated onto the polyamidoamine backbone via piperazine linker. The conjugates were characterized by Fourier transform spectroscopy, energy-dispersive X-ray analysis, atomic force spectroscopy and nuclear magnetic resonance spectroscopy and it confirmed the successful incorporation of the antiproliferative agents onto the carriers. The weight percentage incorporation of bisphosphonate to the carriers was found to be between 2.56% and 3.34%. The in vitro release studies of curcumin from the polyamidoamine conjugate were performed in dialysis bag at selected pH values. The release of curcumin was significantly slower at pH 7.4 when compared to pH 5.8. The release profiles indicate that the conjugates are more stable at pH 7.4 and are potential sustained drug-delivery systems for combination therapy.

Kinetic release studies of nitrogen-containing bisphosphonate from gum acacia crosslinked hydrogels.

Natural polymer hydrogels are useful for controlling release of drugs. In this study, hydrogels containing gum acacia were synthesized by free-radical polymerization of acrylamide with gum acacia. The effect of gum acacia in the hydrogels on the release mechanism of nitrogen-containing bisphosphonate (BP) was studied at pH 1.2 and 7.4. The hydrogels exhibited high swelling ratios at pH 7.4 and low swelling ratios at pH 1.2. The release study was performed using UV-Visible spectroscopy via complex formation with Fe(III) ions. At pH 1.2, the release profile was found to be anomalous while at pH 7.4, the release kinetic of BP was a perfect zero-order release mechanism. The hydrogels were found to be pH-sensitive and the release profiles of the BP were found to be influenced by the degree of crosslinking of the hydrogel network with gum acacia. The preliminary results suggest that these hydrogels are promising devices for controlled delivery of bisphosphonate to the gastrointestinal region.

Synthesis, characterization, and antiplasmodial activity of polymer-incorporated aminoquinolines.

In this research, aminoquinoline compounds were synthesized, characterized, and incorporated into water-soluble polymers to form conjugates. The conjugates were characterized by X-ray diffraction, thermal gravimetric analysis, scanning electron microscope, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy to confirm the successful incorporation of the aminoquinoline compound on to the polymer. The synthesized conjugates were screened for in vitro antiplasmodial activity in triplet test against chloroquine-sensitive strain of Plasmodium falciparum and chloroquine drug was used as a reference drug in all the experiments. A full dose-response was performed to determine the concentration inhibiting 50% of parasite growth (IC50 value). Polymeric conjugates containing 3-diethylamino-1-propylamine solubilizing units were found to be most active against the chloroquine-sensitive strain of P. falciparum.