Background: Nowadays, scientists are trying to design a developed carrier for delivering drugs specifically to cancerous cells. This study aimed to design the poly (acrylamide-maleic anhydride)/(FA & TPGS) coated nanoliposome (P(AAm-MA)/(FA & TPGS) NL) as an FA-modified targeted drug delivery system. Methods: The P(AAm-MA)/(FA & TPGS) copolymer was synthesized via free radical polymerization of AAm and MA, followed by chemical grafting of FA-NH2 and TPGS-SS-NH2. Also, the nanoliposome (NL) was prepared by the thin lipid film hydration method and the Doxorubicin (DOX) was encapsulated into the core of nanoliposome during lipid bilayer formation. After that, the copolymer was used to coat the NL in order to prepare P(AAm-MA)/ (FA & TPGS) NL. The cytotoxicity of DOX-loaded P(AAm-MA)/(FA & TPGS) NL, pure DOX and blank P(AAm-MA)/(FA & TPGS) NL against MCF-7 were measured by MTT assay. The intracellular uptake of free DOX and DOX-loaded P(AAm-MA)/(FA & TPGS) NL against MCF-7 was studied using a fluorescence microscope. Results: The P(AAm-MA)/(FA & TPGS) copolymer was initially investigated by FT-IR, then the TEM analysis of P(AAm-MA)/(FA & TPGS) NL was performed, and showed that the copolymer formed a thin layer around liposomal vesicles. Also, the TEM and DLS results confirmed the preparation of P(AAm-MA)/(FA & TPGS) NL with less than 100 nm diameter. The zeta potential results confirmed the coating of NL with copolymer by electrostatic interactions. The DOXloaded P(AAm-MA)/(FA & TPGS) NL exhibited enhanced cellular uptake through FA-mediated endocytosis. The efficiency of DOX-loaded P(AAm-MA)/(FA & TPGS) NL against MCF-7 was verified by MTT, and exhibited higher cytotoxicity of the DOX-loaded P(AAm-MA)/(FA & TPGS) NL compared to pure DOX. Conclusion: Overall, the P(AAm-MA)/(FA & TPGS) NL controlled MCF-7 cells' growth because of its enhanced cellular uptake via FA-mediated endocytosis. Thus, the prepared nanoliposome carrier can be a suitable choice for inhibiting the growth of cancer cells.
Background: Brain drug delivery is of paramount significance in CNS-related diseases as blood brain barrier (BBB) permeability is not feasible for many pharmaceutical agents. The purpose of this study was to identify peptide sequences with specific translocation property into brain via intranasal route using in vivo phage display method to be used as CNS drug delivery carriers. Methods: To screen peptides with nose-to-brain translocation capability, a 12-mer peptide library displayed on M13 bacteriophage was intranasally administered to anesthetized mice with subsequent recovery of the phage particles from the brain. The identified peptide sequences were analyzed using bioinformatics tools. Results: The results showed that intranasal transport of phage particles to the brain is independence of displayed peptide sequences due to random distribution of residues in different positions of isolated peptides. Nanoscale feature of bacteriophage particles may be responsible for nose-to-brain translocation through olfactory epithelium. Conclusion: Taken together, the results open a route for designing phage-guided therapeutic systems as nanocarriers useful in intranasal brain targeting drug delivery.
Background: Botox’s therapeutic applications are limited by its instability and uncontrolled diffusion into extramuscular tissues. This study aims to develop a polyethylene glycol-based formulation by conjugating Botox to a second-generation anionic linear-globular dendrimer (G2-ALGDs) and evaluate its colloidal stability and muscle localization using technetium-99m radioimaging. Methods: G2-ALGDs were synthesized via N,N′-dicyclohexylcarbodiimide catalysis and conjugated with Botox (D-BTX) using EDC/DCC coupling. Characterization was done by DLS, FTIR, AFM, TEM, and FE-SEM. Stability at 4 °C was monitored for six months using DLS and TEM. Cytocompatibility was assessed by MTT assay in HFF2 cells. D-BTX was radiolabeled with technetium-99m to study purity, stability, and in vivo biodistribution using RT-LC and SPECT imaging. Results: Botox conjugation increased the particle size from 111.6±16.9 nm to 160.0±3.1 nm and shifted the zeta potential from –25.2±1.63 mV to+17.16±1.24 mV. FTIR confirmed amide bond formation at 1649 cm⁻¹. D-BTX was much less cytotoxic than free Botox at 0.001 ng/mL (p=0.0013), but no difference was observed at higher concentrations. The formulation exhibited physical stability for six months at 4°C. The radiolabeled formulation was up to 90.85% pure and remained stable for 24 h. SPECT imaging revealed improved localization of D-BTX within the muscle. After 12 h, D-BTX exhibited maximum signal intensity with minimal dispersion, indicative of controlled diffusion at the injection site. Conclusion: This PEGylated dendrimer-Botox nanoconjugate provides a stable, muscle-targeting, and imageable platform, which surmounts some of the main drawbacks in current clinical applications.
Background: Ivermectin (IVM) is a broad-spectrum antiparasitic drug used in humans and animals to treat infections like scabies, river blindness, and various worms. Derived from avermectin via fermentation, IVM contains impurities and degradation products. During pandemics like COVID-19, demand for IVM formulations surges, requiring specialized manufacturing. Classified as a Biopharmaceutics Class II drug, IVM has high permeability but low solubility, leading to poor dissolution and variable absorption, impacting efficacy. Enhancing solubility can improve bioavailability and aid in purification, crystallization, and analysis. Thus, optimizing IVM formulations is crucial for better therapeutic outcomes. Methods: This work investigated the IVM solubility in binary mixtures of ethylene glycol and water, at a temperature range of 298.2 K to 313.2 K. A laser-based robotic system was employed to measure the solubility data. The generated solubility values were presented utilizing various thermodynamic models, such as the van't Hoff, mixture response surface, Jouyban-Acree, Jouyban-Acree-van't Hoff, and modified Wilson models. Several thermodynamic factors, including Delta G degrees, Delta H degrees, and Delta S degrees were also computed according to the experimental findings. Results: The results showed that in the EG -rich mixtures and proportional to temperature, the IVM solubility significantly increased. The mathematical models effectively estimated IVM solubility in binary solvents, with MRD% ranging from 5.7 to 13.7. Thermodynamic analysis revealed non-spontaneous dissolution, and endothermic reaction for IVM dissolution in the investigated mixtures. Conclusion: These properties offered valuable insights into the energetic characteristics of the dissolution process and computed utilizing the Gibbs and van't Hoff equations.
