A Novel PEtOx-Based Nanogel Targeting Prostate Cancer Cells for Drug Delivery.

This study focuses on creating a specialized nanogel for targeted drug delivery in cancer treatment, specifically targeting prostate cancer. This nanogel (referred to as SGK 636/Peptide 563/PEtOx nanogel) is created using hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) through a combination of living/cationic ring-opening polymerization (CROP) and alkyne-azide cycloaddition (CuAAC) "click" chemical reactions. A fluorescent probe (BODIPY) is also conjugated with the nanogel to monitor drug delivery. The characterizations through 1 H-NMR, and FT-IR, SEM, TEM, and DLS confirm the successful production of uniform, and spherical nanogels with controllable sizes (100 to 296 nm) and stability in physiological conditions. The biocompatibility of nanogels is evaluated using MTT cytotoxicity assays, revealing dose-dependent cytotoxicity. Drug-loaded nanogels exhibited significantly higher cytotoxicity against cancer cells in vitro compared to drug-free nanogels. Targeting efficiency is examined using both peptide-conjugated and peptide-free nanogels, with the intracellular uptake of peptide 563-conjugated nanogels by tumor cells being 60-fold higher than that of nanogels without the peptide. The findings suggest that the prepared nanogel holds great potential for various drug delivery applications due to its ease of synthesis, tunable functionality, non-toxicity, and enhanced intracellular uptake in the tumor region.

Recent Strategies for Cancer Therapy: Polymer Nanoparticles Carrying Medicinally Important Phytochemicals and Their Cellular Targets.

Cancer is a leading cause of death in the world today. In addition to the side effects of the chemotherapeutic drugs used to treat cancer, the development of resistance to the drugs renders the existing drugs ineffective. Therefore, there is an urgent need to develop novel anticancer agents. Medicinally important phytochemicals such as curcumin, naringenin, quercetin, epigallocatechin gallate, thymoquinone, kaempferol, resveratrol, genistein, and apigenin have some drawbacks, including low solubility in water, stability and bioavailability issues, despite having significant anticancer effects. Encapsulation of these natural compounds into polymer nanoparticles (NPs) is a novel technology that could overcome these constraints. In comparison to the free compounds, phytochemicals loaded into nanoparticles have greater activity and bioavailability against many cancer types. In this review, we describe the preparation and characterization of natural phytochemical-loaded polymer NP formulations with significant antioxidant and anti-inflammatory effects, their in vitro and in vivo anticancer activities, as well as their possible cellular targets.

Bacteriophage Therapy of Bacterial Infections: The Rediscovered Frontier.

Antibiotic-resistant infections present a serious health concern worldwide. It is estimated that there are 2.8 million antibiotic-resistant infections and 35,000 deaths in the United States every year. Such microorganisms include Acinetobacter, Enterobacterioceae, Pseudomonas, Staphylococcus and Mycobacterium. Alternative treatment methods are, thus, necessary to treat such infections. Bacteriophages are viruses of bacteria. In a lytic infection, the newly formed phage particles lyse the bacterium and continue to infect other bacteria. In the early 20th century, d'Herelle, Bruynoghe and Maisin used bacterium-specific phages to treat bacterial infections. Bacteriophages are being identified, purified and developed as pharmaceutically acceptable macromolecular "drugs," undergoing strict quality control. Phages can be applied topically or delivered by inhalation, orally or parenterally. Some of the major drug-resistant infections that are potential targets of pharmaceutically prepared phages are Pseudomonas aeruginosa, Mycobacterium tuberculosis and Acinetobacter baumannii.

Oxytocin-loaded sustained-release hydrogel graft provides accelerated bone formation: An experimental rat study.

Restoration of the lost bone volume is one of the most deliberate issues in dentistry. Sustained-release microspherical oxytocin hormone in a poloxamer hydrogel scaffold combined with a mixture of ß-tricalcium phosphate and hydroxyapatite (CP) may serve as a suitable bone graft. The aim of this study was to design and test a novel thermosensitive hydrogel graft incorporating oxytocin-loaded poly(d, l-lactide-co-glycolide) (PLGA) sustained-release microspheres and CP. Thermosensitive poloxamer hydrogel containing CP (HCP graft) was prepared as a base and combined with hollow microspheres (HCPM) and oxytocin-loaded microspheres (HCPOM). Eighty Wistar rats were used for testing the grafts and a control group in 8-mm-diameter critical-sized calvarial defects (CSD); (n = 20). Bone healing at the 4th and 8th weeks was evaluated by histological, histomorphometric, and radiological (micro-computed tomography [µCT]) analyses. The results were analyzed by two-way analysis of variance (P < .05). Oxytocin-loaded PLGA microspheres prepared by the solvent displacement method yielded a high encapsulation efficiency of 89.5% and a slow drug release. Incorporation of the microspheres into the hydrogel graft slowed the release rate down and the release completed within 32 days. HCPOM revealed the highest new bone formation (26.45% ± 6.65% and 30.76% ± 4.37% at the 4th and 8th weeks, respectively; P < .0001) while HCPM and HCP groups revealed a bone formation of around 10% (P > .05). µCT findings of HCPOM group showed the highest mean bone mineral density values (42.21 ± 5.14 and 46.94 ± 3.30 g/cm3 for the 4th and 8th weeks, respectively; P < .0027). The proposed oxytocin-loaded sustained-release PLGA microspheres containing thermosensitive hydrogel graft (HCPOM) provide an accelerated bone regeneration in the rat calvaria.

The efficacy of sustained-release chitosan microspheres containing recombinant human parathyroid hormone on MRONJ.

Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient's symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.

Modified chitosan-based nanoadjuvants enhance immunogenicity of protein antigens after mucosal vaccination.

Nasal vaccination is considered to be an effective and convenient way of increasing immune responses both systemically and locally. Although various nanovaccine carriers have been introduced as potential immune adjuvants, further improvements are still needed before they can be taken to clinical usage. Chitosan-based nanovaccine carriers are one of the most widely studiedadjuvants, owing to the abilityof chitosan toopen tight junctions between nasal epithelial cells and enhance particle uptake as well as its inherent immune activating role. In present study, bovine serum albumin (BSA) loaded nanoparticles were prepared using novel aminated (aChi) and aminated plus thiolated chitosan (atChi) polymers, to further enhance mucoadhesiveness and adjuvanticity of the vaccine system by improving electrostatic interactions of polymers with negatively charged glycoproteins. Nanocarriers with optimum size and surface charge, high encapsulation efficiency of model antigen and good stability were developed. Negligible toxicity was observed in Calu-3 and A549 cell lines. In vivo studies, revealed high levels of systemic antibodies (IgG, IgG1 and IgG2a) throughout the study and presence of sIgA in vaginal washes showed that common mucosal system was successfully stimulated. Cytokine levels indicated a mixed Th1/Th2 immune response. A shift towards cellular immune responses was observed after nasal immunisation with antigen loaded nanoparticle formulations. These nanoparticles exhibit great potential for nasal application of vaccines.

The efficacy of sustained-release chitosan microspheres containing recombinant human parathyroid hormone on MRONJ

Abstract Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient's symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.

Nasal vaccination with poly(ß-amino ester)-poly(d,l-lactide-co-glycolide) hybrid nanoparticles.

Mucosal vaccination stimulates both mucosal and systemic immunity. However, mucosal applications of vaccine antigens in their free form generally result in poor systemic immune responses and need adjuvantation. In this study, bovine serum albumin loaded, new hybridised poly(ß-amino ester)-poly(d,l-lactide-co-glycolide) nanoparticles were prepared by double emulsion-solvent evaporation method, characterised and evaluated in vivo as nasal vaccine carriers. Cationic spherical particles with a mean size of 240nm, good physical stability and high encapsulation efficiency were obtained. Protein structure was not affected throughout preparation and minimal toxicity was shown in Calu-3 and A549 cells. Nasal vaccination with these nanoparticles revealed markedly higher humoral immune responses compared with free antigen following intranasal and subcutaneous immunisation. Mucosal immune response was also stimulated and cytokine titres indicated that Th1 and Th2 pathways were successfully activated. This study shows that the formulated hybrid nanoparticles can be a promising carrier for nasal immunisation of poor antigenic proteins.