PLGA-based drug delivery system for combined therapy of cancer: research progress

In recent years, PLGA micro/nano particle drug delivery systems has been widely used in cancer treatment. According to the unique properties of PLGA, carriers of various structures are designed to keep the function of drugs or bioactive substances, ensure the effective load of molecules and improve the bioavailability of drugs in diseased parts. PLGA is one of the earliest and most commonly used biodegradable materials. It is often used for functional modification with other polymers (such as polyethylene glycol and chitosan) or other molecules (such as aptamers and ligands) to deliver various small molecule drugs (such as DOX and DTX) and bioactive macromolecules (such as proteins and nucleic acids) to improve targeting, controlled release and therapeutic properties. In this paper, the preparation methods, physical and chemical properties and medical applications of PLGA micro/nano particles are discussed. We focused on the recent research progress of the PLGA-based drug carrier system in tumor combination therapy.

Copolymer Involving 2-Hydroxyethyl Methacrylate and 2-Chloroquinyl Methacrylate: Synthesis, Characterization and In Vitro 2-Hydroxychloroquine Delivery Application

The Poly(2-chloroquinyl methacrylate-co-2-hydroxyethyl methacrylate) (CQMA-co-HEMA) drug carrier system was prepared with different compositions through a free-radical copolymerization route involving 2-chloroquinyl methacrylate (CQMA) and 2-hydroxyethyl methacrylate) (HEMA) using azobisisobutyronitrile as the initiator. 2-Chloroquinyl methacrylate monomer (CQMA) was synthesized from 2-hydroxychloroquine (HCQ) and methacryloyl chloride by an esterification reaction using triethylenetetramine as the catalyst. The structure of the CQMA and CQMA-co-HEMA copolymers was confirmed by a CHN elementary analysis, Fourier transform infra-red (FTIR) and nuclear magnetic resonance (NMR) analysis. The absence of residual aggregates of HCQ or HCQMA particles in the copolymers prepared was confirmed by a differential scanning calorimeter (DSC) and XR-diffraction (XRD) analyses. The gingival epithelial cancer cell line (Ca9-22) toxicity examined by a lactate dehydrogenase (LDH) assay revealed that the grafting of HCQ onto PHEMA slightly affected (4.2–9.5%) the viability of the polymer carrier. The cell adhesion and growth on the CQMA-co-HEMA drug carrier specimens carried out by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay revealed the best performance with the specimen containing 3.96 wt% HCQ. The diffusion of HCQ through the polymer matrix obeyed the Fickian model. The solubility of HCQ in different media was improved, in which more than 5.22 times of the solubility of HCQ powder in water was obtained. According to Belzer, the in vitro HCQ dynamic release revealed the best performance with the drug carrier system containing 4.70 wt% CQMA.

Development and evaluation of Pharmacosome formulations of Mefenamic acid

Patience who suffered from menstrual pain disease is generally prescribed the non-steroidal anti-inflammatory drug (NSAIDs). Monorrhagia or another blood disorder & some gynecological disorder, which impairs body function and acts as an economic burden. Due to respective use of ACE by oral route, it may cause GI complication such as bleeding, pain, perforation, abdominal pain, and swelling. To decrease the side effect of ACE, it is given by topical route in promotes the safety & efficacy of the ACE. The Mefenamic Acid pharmacosomes were prepared by the hand shaking method technique and evaluated by various methods such as in-vitro release study, % yield, drug entrapment efficiency, pH of the prepared formulation. The prepared system was also characterized by FTIR spectrophotometer to identify the drug-excipients interaction. The maximum entrapment efficiency of pharmacosomes was found to be 90%. The main aim of this study was to develop and characterized a vesicular drug carrier system for topical delivery of Mefenamic Acid to overcome the problem related with oral route.

Adsorption of doxepin drug on the surface of B12N12 and Al12N12 nanoclusters: DFT and TD-DFT perspectives

The adsorption of Doxepin (DOX) drug on the surfaces of B12N12 and Al12N12 nanoclusters was studied by using DFT and TD-DFT calculations at the B3PW91 method and 6–31 + G * basis set in the solvent (water). The adsorption effect of the DOX drug on the bond lengths, electronic properties, and dipole moment of the B12N12 and Al12N12 nanoclusters was studied. The change in λ max was assessed by an investigation of calculated UV spectra. NBO analysis displayed a charge transfer between DOX and two nanoclusters. The LOL and ELF values of the B–N bond are the greater than B–O, Al–O, and Al–N bonds, confirming stronger interaction between the boron atom of B12N12 nanocluster and the nitrogen atom of the DOX drug. It is found that the B12N12 nanocluster can be suitable as a drug carrier system for the delivery of DOX drug. The results of our study can be used to design a suitable carrier for the DOX drug.

Formulation and Evaluation of Aceclofenac Liposomes

Patients who suffered from rheumatic disease and osteoarthritis are generally prescribed the non-steroidal anti-inflammatory drug (NSAIDs). Osteoarthritis is a common musculoskeletal disorder, which impairs body function and acts as an economic burden. Due to the repetitive use of ACE by oral route, it may cause gastrointestinal complications such as ulceration, bleeding, pain, perforation. To decrease the side effects of ACE, it is given by topical route in the form of ointment. This review highlights reducing gastrointestinal problems and promotes the safety and efficacy of the ACE. The Aceclofenac liposomes were prepared by the thin film hydration technique and evaluated by various methods such as in- vitro release study, % yield, drug entrapment efficiency, pH of the prepared formulation. The prepared system was also characterized by Fourier transform infra-red spectrophotometer to identify the drug- excipients interaction. The maximum entrapment efficiency of liposomes was found to be 90%. The main aim of this study was to develop and characterized a vesicular drug carrier system for topical delivery of Aceclofenac to overcome the problem related with oral route. Keywords: Liposomes, Aceclofenac, topical delivery, transdermal delivery, rheumatic disease and osteoarthritis

Screening of Electrolyte Complexes Formed Between Dextran Sulfate and Amine Structures of Small-Molecule Drugs

Formation of an electrolyte complex using the electrostatic interactions between a polyanionic polymer and a cationic drug is a simple and efficient method of preparing a colloidal drug carrier system. Dextran sulfate, with a negatively charged sulfate group, was reacted in an acetate buffer solution of pH 3 with positively charged 1° amine, 2° amine, 3° amine, piperazine, and piperidine structures from 24 small-molecule drugs. The electrolyte complex was formed from 15 drugs, 63% of those tested. The tendency to form the electrolyte complex was in the order of piperazine and piperidine >3° amine >>2° amine. The drugs with the 1° amine structure failed to form an electrolyte complex. The mean particle sizes were in the range of 50-740 nm, and most of them showed a submicron colloidal dispersion of <400 nm. Regarding drug encapsulation efficiency (%), 11 drugs with piperazine, piperidine, and 3° amine structures showed 60–98% efficiency, which was fairly high. The results suggest that directly forming the electrolyte complex with dextran sulfate yields promising structural attributes as a submicron colloidal drug carrier system.

Experimental study on nuclear-targeted plasmid-based short hairpin RNA (ShRNA) to hypoxia inducible factor-1α (PshHIF-1α) PshHIF-1α nano-drug carrier system for breast cancer treatment in rats

This study was aimed at exploring the regulatory mechanism of auclear-targeted pshHIF-1α nano-drug carrier system (NPNCS) in the treatment of breast cancer in rats. MDA-MB-231 cell was cultured and DJ-1 and PTEN mRNA level was detected by qRT-PCR along with analysis of cell viability by CCK-8 and apoptosis by means of flow cytometry. The rats were assigned into control group, nuclear-targeted pshHIF-1α nanopharmaceutical system treatment group, and nuclear-targeted pshHIF-1α nano-pharmaceutical system+PTEN inhibitor SF1670 group, followed by analysis of cell proliferation by EdU staining, cell apoptosis by flow cytometry, and the levels of DJ-1, PTEN, and p-AKT. Compared with MDA-MB-231 cells treated with NPNCS, cells without intervention showed decreased PTEN and increased DJ-1 level. NPNCS induced cell apoptosis. Administration of nuclear-targeted pshHIF-1α nano-drug delivery system down-regulated DJ-1 and up-regulated PTEN. Combined treatment with SF1670 promoted p-AKT level and decreased the inhibitory effect of NPNCS on p-AKT level. In conclusion, the nuclear-targeted pshHIF-1α nano-drug delivery system down-regulated DJ-1 and exerted a tumor suppressor and pro-apoptotic effect, which wasrelated to p-AKT phosphorylation and up-regulation of PTEN.