PLGA Nanoparticles Research Articles

Oral administration of recombinant outer membrane protein A-based nanovaccine affords protection against Aeromonas hydrophila in zebrafish.

Aeromonas hydrophila, an opportunistic warm water pathogen, has always been a threat to aquaculture, leading to substantial economic losses. Vaccination of the cultured fish would effectively prevent Aeromoniasis, and recent advancements in nanotechnology show promise for efficacious vaccines. Oral delivery would be the most practical and convenient method of vaccine delivery in a grow-out pond. This study studied the immunogenicity and protective efficacy of a nanoparticle-loaded outer membrane protein A from A. hydrophila in the zebrafish model. The protein was over-expressed, purified, and encapsulated using poly lactic-co-glycolic acid (PLGA)nanoparticles via the double emulsion method. The PLGA nanoparticles loaded with recombinant OmpA (rOmpA) exhibited a size of 295 ± 15.1nm, an encapsulation efficiency of 72.52%, and a polydispersity index of 0.292 ± 0.07. Scanning electron microscopy confirmed the spherical and isolated nature of the PLGA-rOmpA nanoparticles. The protective efficacy in A. hydrophila-infected zebrafish after oral administration of the nanovaccine resulted in relative percentage survival of 77.7. Gene expression studies showed significant upregulation of immune genes in the vaccinated fish. The results demonstrate the usefulness of oral administration of nanovaccine-loaded rOmpA as a potential vaccine since it induced a robust immune response and conferred adequate protection against A. hydrophila in zebrafish, Danio rerio.

Enhanced Prostate-specific Membrane Antigen Targeting by Precision Control of DNA Scaffolded Nanoparticle Ligand Presentation.

Targeted nanoparticles have been extensively explored for their ability to deliver their payload to a selective cell population while reducing off-target side effects. The design of actively targeted nanoparticles requires the grafting of a ligand that specifically binds to a highly expressed receptor on the surface of the targeted cell population. Optimizing the interactions between the targeting ligand and the receptor can maximize the cellular uptake of the nanoparticles and subsequently improve their activity. Here, we evaluated how the density and presentation of the targeting ligands dictate the cellular uptake of nanoparticles. To do so, we used a DNA-scaffolded PLGA nanoparticle system to achieve efficient and tunable ligand conjugation. A prostate-specific membrane antigen (PSMA) expressing a prostate cancer cell line was used as a model. The density and presentation of PSMA targeting ligand ACUPA were precisely tuned on the DNA-scaffolded nanoparticle surface, and their impact on cellular uptake was evaluated. It was found that matching the ligand density with the cell receptor density achieved the maximum cellular uptake and specificity. Furthermore, DNA hybridization-mediated targeting chain rigidity of the DNA-scaffolded nanoparticle offered ∼3 times higher cellular uptake compared to the ACUPA-terminated PLGA nanoparticle. Our findings also indicated a ∼ 3.7-fold reduction in the cellular uptake for the DNA hybridization of the non-targeting chain. We showed that nanoparticle uptake is energy-dependent and follows a clathrin-mediated pathway. Finally, we validated the preferential tumor targeting of the nanoparticles in a bilateral tumor xenograft model. Our results provide a rational guideline for designing actively targeted nanoparticles and highlight the application of DNA-scaffolded nanoparticles as an efficient active targeting platform.

Microporation-Mediated Transdermal Delivery of In Situ Gel Incorporating Etodolac-Loaded PLGA Nanoparticles for Management of Rheumatoid Arthritis.

Management of rheumatoid arthritis (RA) requires long-term administration of different medications since there has been no cure until now. Etodolac (ETD) is a nonsteroidal anti-inflammatory drug commonly used for RA management. However, its long-term administration resulted in severe side effects. This study aimed to develop a transdermal in situ gel incorporating ETD-loaded polymeric nanoparticles (NPs) to target the affected joints for long-term management of RA. Several PLGA NPs incorporating 1% ETD were prepared by nanoprecipitation and optimized according to the central composite design. The optimum NPs (F1) exhibited 96.19 ± 2.31% EE, 282.3 ± 0.62 nm PS, 0.383 ± 0.04 PDI, and -6.44 ± 1.69 ZP. A hyaluronate coating was applied to F1 (H-F1) to target activated macrophages at inflammation sites. H-F1 exhibited 287.4 ± 4.2 nm PS, 0.267 ± 0.02 PDI, and -23.7 ± 3.77 ZP. Pluronic F-127 in situ gel (H-F1G) showed complete gelation at 29 °C within 5 min. ETD permeation from H-F1G was sustained over 48 h when applied to microporated skin and exhibited significant enhancement of all permeation parameters. Topical application of H-F1G (equivalent to 8 mg ETD) to Wistarrat microporated skin every 48 h resulted in antirheumatic therapeutic efficacy comparable to commercial oral tablets (10 mg/kg/day).

Modification of mesenchymal stromal cells with silibinin-loaded PLGA nanoparticles improves their therapeutic efficacy for cutaneous wound repair

The use of mesenchymal stromal cells (MSCs) for treating chronic inflammatory disorders, wounds, and ischemia-reperfusion injuries has shown improved healing efficacy. However, the poor survival rate of transplanted cells due to oxidative stress in injured or inflamed tissue remains a significant concern for MSC-based therapies. In this study, we developed a new approach to protect MSCs from oxidative stress, thereby improving their survival in a wound microenvironment and enhancing their therapeutic effect. We produced PLGA nanoparticles loaded with the cytoprotective phytochemical silibinin (SBN), and used them to modify MSCs. Upon internalization, these nanoformulations released SBN, activating the Nrf2/ARE signaling pathway, resulting in threefold reduction in intracellular ROS content and improved cell survival under oxidative stress conditions. Modification of MSCs with SBN-loaded PLGA nanoparticles increased their survival upon transplantation to full-thickness cutaneous wounds and improved wound healing. This study suggests that MSC modification with cytoprotective nanoparticles could be a promising approach for improving wound healing.

PLGA-LEC/F127 hybrid nanoparticles loaded with curcumin and their modulatory effect on monocytes.

Aim: To investigate the effect of surfactant type on curcumin-loaded (CUR) PLGA nanoparticles (NPs) to modulate monocyte functions. Materials & methods: The nanoprecipitation method was used, and PLGA NPs were designed using PluronicF127 (F127) and/or lecithin (LEC) as surfactants. Results: The Z-average of the NPs was <200nm, they had a spherical shape, Derjaguin-Muller-Toporov modulus >0.128MPa, they were stable during storage at 4°C, ζ-potential ∼-40mV, polydispersity index <0.26 and % EE of CUR >94%. PLGA-LEC/F127NPs showed favorable physicochemical and nanomechanical properties. These NPs were bound and internalized mainly by monocytes, suppressed monocyte-induced reactive oxygen species production,and decreased the ability of monocytes to modulate T-cell proliferation. Conclusion: These results demonstrate the potential of these NPs for targeted therapy.

Development, Optimization, and in vitro Evaluation of Silybin-loaded PLGA Nanoparticles and Decoration with 5TR1 Aptamer for Targeted Delivery to Colorectal Cancer Cells.

Chemotherapeutic agents often lack specificity, intratumoral accumulation, and face drug resistance. Targeted drug delivery systems based on nanoparticles (NPs) mitigate these issues. Poly (lactic-co-glycolic acid) (PLGA) is a well-studied polymer, commonly modified with aptamers (Apts) for cancer diagnosis and therapy. In this study, silybin (SBN), a natural agent with established anticancer properties, was encapsulated into PLGA NPs to control delivery and improve its poor solubility. The field-emission scanning electron microscopy (FE-SEM) showed spherical and uniform morphology of optimum SBN-PLGA NPs with 138.57±1.30nm diameter, 0.202±0.004 polydispersity index (PDI), -16.93±0.45mV zeta potential (ZP), and 70.19±1.63% entrapment efficiency (EE). The results of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) showed no chemical interaction between formulation components, and differential scanning calorimetry (DSC) thermograms confirmed efficient SBN entrapment in the carrier. Then, the optimum formulation was functionalized with 5TR1 Apt for active targeted delivery of SBN to colorectal cancer (CRC) cells in vitro. The SBN-PLGA-5TR1 nanocomplex released SBN at a sustained and constant rate (zero-order kinetic), favoring passive delivery to acidic CRC environments. The MTT assay demonstrated the highest cytotoxicity of the SBN-PLGA-5TR1 nanocomplex in C26 and HT29 cells and no significant cytotoxicity in normal cells. Apoptosis analysis supported these results, showing early apoptosis induction with SBN-PLGA-5TR1 nanocomplex which indicated this agent could cause programmed death more than necrosis. This study presents the first targeted delivery of SBN to cancer cells using Apts. The SBN-PLGA-5TR1 nanocomplex effectively targeted and suppressed CRC cell proliferation, providing valuable insights into CRC treatment without harmful effects on healthy tissues.

Development of PSL-Loaded PLGA Nanoparticles for the Treatment of Allergic Contact Dermatitis

Allergic contact dermatitis (ACD) can easily develop once sensitization is established by exposure to small amounts of antigen, and steroids are used for treatment. In this study, we evaluated the therapeutic efficacy of prednisolone (PSL)-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles (NPs) on a mouse model of contact dermatitis (CHS). Nanoparticles were prepared using a poor solvent diffusion method, and particle size distribution and mean particle size were measured using dynamic light scattering. Treatment experiments with PSL-loaded PLGA NPs were performed before and after sensitization with 1-fluoro-2,4-dinitrobenzene (DNFB), and evaluation was performed by quantifying intracutaneous IL-4 and TNF-α levels in a mouse model of CHS using ELISA. When PSL-loaded PLGA NPs were administered before sensitization, IL-4 expression was significantly decreased, and TNF-α tended to decrease in the group treated with PSL-loaded PLGA NPs compared to the non-treated group. When PSL-loaded PLGA NPs were administered after sensitization, IL-4 expression was significantly decreased in the group treated with PSL-loaded PLGA NPs compared to the non-treated group. In both cases, there were no significant differences between the PSL-loaded PLGA NP treatment group and the PSL-containing ointment group. These results suggest that, in the treatment of CHS, PSL-loaded PLGA NPs show a certain therapeutic effect when preadministration.

Targeting Inflammatory Lesions Facilitated by Galactosylation Modified Delivery System Eudragit/Gal-PLGA@Honokiol for the treatment of Ulcerative Colitis

Honokiol (HNK) is one of the bioactive ingredients from the well-known Chinese herbal medicine Magnolia officinalis, and its research interests is rising for its extensive pharmacological activities, including novel therapeutic effect on ulcerative colitis (UC). However, further application of HNK is largely limited by its unique physicochemical properties, such as poor water solubility, low bioavailability, as well as unsatisfied targeting efficacy for inflammatory lesions. In this study, we constructed galactosylation modified PLGA nanoparticles delivery system for efficient target delivery of HNK to the colitic lesions, which could lay a research foundation for the deep development of HNK for the treatment of UC. D-galactose was grafted by chemical coupling reactions with PLGA to prepare Gal-PLGA, which was used as a carrier for HNK (Gal-PLGA@HNK nanoparticles (NPs)). To improve the colon targeting efficiency by oral administration of the NPs, Eudragit S100 was used for wrapping on the surface of Gal-PLGA@HNK NPs (E/Gal-PLGA@HNK NPs). Our results showed that the encapsulation efficiency and drug loading capacity of E/Gal-PLGA@HNK NPs were 90.72 ± 0.54% and 8.41 ± 0.02%, respectively. Its average particle size was 242.24 ± 8.42 nm, with a PDI value of 0.135 ± 0.06 and zeta-potential of -16.83 ± 1.89 mV. The release rate of HNK from E/Gal-PLGA@HNK NPs was significantly decreased when compared with that of free HNK in simulated gastric and intestinal fluids, which displayed a slow-releasing property. It was also found that the cellular uptake of E/Gal-PLGA@HNK NPs was significantly increased when compared with that of free HNK in RAW264.7 cells, which was facilitated by D-galactose grafting on the PLGA carrier. Additionally, our results showed that E/Gal-PLGA@HNK NPs significantly improved colonic atrophy, body weight loss, as well as reducing disease activity index (DAI) score and pro-inflammatory cytokine levels in UC mice induced by DSS. Besides, the retention time of E/Gal-PLGA@HNK NPs in the colon was significantly increased when compared with that of other preparations, suggesting that these NPs could prolong the interaction between HNK and the injured colon. Taken together, the efficiency for target delivery of HNK to the inflammatory lesions was significantly improved by galactosylation modification on the PLGA carrier, which provided great benefits for the alleviation of colonic inflammation and injury in mice.

The influence of various polymer coatings on the in vitro and in vivo properties of PLGA nanoparticles: Comprehensive study

Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) with various surface chemistry are widely used in biomedicine for theranostic applications. The nature of the external coating of nanoparticles has a significant influence on their efficiency as drug carriers or visualization agents. However, information about the mechanisms of nanoparticle accumulation in tumors and the influence of their surface properties on biodistribution is scarce due to the lack of systematic evaluation. Here we investigate the effect of different polymer coatings of the surface on in vitro and in vivo properties of PLGA nanoparticles. Namely, cell binding efficiency, cytotoxicity, efficiency of fluorescent bioimaging, and tumor accumulation were tested. The highest binding efficiency in vitro and cytotoxicity were observed for positively charged polymers. Interestingly, in vivo fluorescent visualization of tumor-bearing mice and quantitative measurements of biodistribution of magnetite-loaded nanoparticles indicated different dependences of accumulation in tumors on the coating of PLGA nanoparticles. This means that nanoparticle surface properties can simultaneously enhance imaging efficiency and decrease quantitative accumulation in tumors. The obtained data demonstrate the complexity of the dependence of nanoparticles’ effectiveness for theranostic applications on surface features. We believe that this study will contribute to the rational design of nanoparticles for effective cancer diagnostics and therapy.

Impact of antigen loading in tolerogenic nanoparticles to mitigate Th2-mediated allergic lung inflammation.

Allergic disease is a major global health concern that imposes significant life-altering and economic burdens on affected individuals. However, there is still no cure. Polymer-based nanoparticles (NP) have shown the potential to induce antigen (Ag)-specific immune tolerance in various Th1/17 and Th2-mediated immune disorders including autoimmunity and allergy. Common methods by which Ags are associated with NPs are through surface conjugation or encapsulation. However, these Ag delivery strategies can be associated with several caveats that dampen their effectiveness such as uncontrolled Ag loading, a high Ag burst release, and an increased immune recognition profile. We previously developed Ag-polymer conjugate NPs (acNPs) to overcome those noted limitations, while allowing for controlled delivery of precise quantities of Ag to innate immune cells for Ag-specific CD4 T cell modulation. Here, we utilized ovalbumin (OVA) protein-poly(lactic-co-glycolic acid) (PLGA) conjugate NPs (acNP-OVA) to elucidate the impact of Ag loading on the induction of Th2 tolerance using a prophylactic and therapeutic OVA/ALUM-induced mouse model of allergic lung inflammation (ALI) in comparison to Ag-encapsulated PLGA NPs (NP(Ag)). We demonstrate that acNP-OVA formulations reduced OVA-specific IgE and inhibited Th2 cytokine secretions in an Ag loading-dependent manner when administered prophylactically. Administration of acNP-OVA to pre-sensitized mice did not affect OVA-specific IgE and Th2 cytokines tended to be reduced, however, there was no clear Ag loading dependency. acNP-OVA with medium-to-low Ag loadings were well tolerated, while formulations with high Ag loadings, including NP(Ag) resulted in anaphylaxis. Overall, our results clarify the relationship between Ag loading and Ag-specific IgE and Th2 cytokine responses in a murine model of ALI, which provides insight useful for future design of tolerogenic NP-based immunotherapies.

Improving the Antimicrobial Potency of Berberine for Endodontic Canal Irrigation Using Polymeric Nanoparticles.

To address the challenges posed by biofilm presence and achieve a substantial reduction in bacterial load within root canals during endodontic treatment, various irrigants, including nanoparticle suspensions, have been recommended. Berberine (BBR), a natural alkaloid derived from various plants, has demonstrated potential applications in dentistry treatments due to its prominent antimicrobial, anti-inflammatory, and antioxidant properties. This study aimed to produce and characterize a novel polymeric nanoparticle of poly (lactic-co-glycolic acid) (PLGA) loaded with berberine and evaluate its antimicrobial activity against relevant endodontic pathogens, Enterococcus faecalis, and Candida albicans. Additionally, its cytocompatibility using gingival fibroblasts was assessed. The polymeric nanoparticle was prepared by the nanoprecipitation method. Physicochemical characterization revealed spheric nanoparticles around 140 nm with ca, -6 mV of surface charge, which was unaffected by the presence of BBR. The alkaloid was successfully incorporated at an encapsulation efficiency of 77% and the designed nanoparticles were stable upon 20 weeks of storage at 4 °C and 25 °C. Free BBR reduced planktonic growth at ≥125 μg/mL. Upon incorporation into PLGA nanoparticles, 20 μg/mL of [BBR]-loaded nanoparticles lead to a significant reduction, after 1 h of contact, of both planktonic bacteria and yeast. Sessile cells within biofilms were also considered. At 30 and 40 μg/mL, [BBR]-loaded PLGA nanoparticles reduced the viability of the sessile endodontic bacteria, upon 24 h of exposure. The cytotoxicity of BBR-loaded nanoparticles to oral fibroblasts was negligible. The novel berberine-loaded polymeric nanoparticles hold potential as a promising supplementary approach in the treatment of endodontic infections.

Comparison of cell delivery and cell membrane camouflaged PLGA nanoparticles in the delivery of shikonin for colorectal cancer treatment

Inspired by the "natural camouflage" strategy, cell-based biomimetic drug delivery systems (BDDS) have shown great potential in cancer therapy. Red blood cell (RBC) delivery vehicles and red blood cell membrane (RBCm)-camouflaged vehicles were commonly used strategies for drug delivery. We prepared shikonin-encapsulated PLGA nanoparticles (PLGA/SK) with different surface charges to obtain both RBC delivery and RBCm-camouflaged PLGA NPs. The physicochemical properties, in vivo circulation and antitumor effects of these biomimetic preparations were studied. Since the positive PLGA NPs may affect the morphology and function of RBCs, the biomimetic preparations prepared by the negative PLGA NPs showed better in vitro stability. However, positive PLGA NP-based biomimetic preparations exhibited longer circulation time and higher tumor region accumulation, leading to stronger anti-tumor effects. Meanwhile, the RBC delivery PLGA(+) NPs possessed better in vitro cytotoxicity, longer circulation time and higher tumor accumulation than RBCm-camouflaged PLGA(+) NPs. Collectively, RBC delivery vehicles possessed more potential than RBCm-camouflaged vehicles on drug delivery for tumor treatment, especially with positive NPs-loaded.

Surface decoration of PLGA nanoparticles enables efficient transport of floxuridine oligomers into mammalian cells

2′-deoxy-5-fluorouridine (Floxuridine, FdU) oligomers are repeated FdU residues linked to each other through phosphate groups exhibiting anticancer properties. One of the major hurdles exhibited by natural oligomers is their reduced stability and limited ability to impart cellular uptake. To overcome these drawbacks, electrostatic and covalent strategies have been used to combine oligomers with nanoparticles (NPs) to enhance stability and cellular internalization. Polymeric NPs, prepared from oil-in-water (O/W) PLGA nano-emulsions (NEs) using low-energy emulsification methods, have shown potential in many biomedical applications owing to their ability to transport drugs across cellular membranes. Carbodiimide-mediated amine coupling reaction and thiol-based Michael-type addition were used to attach FdU oligomers formed by five FdU residues (FdU5) to PLGA NPs. Colloidally stable dispersions of FdU5-decorated PLGA NPs were obtained and characterized in terms of size, surface charge, and morphology in physiological medium. Additionally, synthetic strategies were envisaged to functionalize the surface of FdU5-decorated polymeric NPs with folic acid (FA). Cell culture experiments showed that FdU5-decorated PLGA NPs were able to internalize efficiently inducing cytotoxic effect and inhibiting cell proliferation in tumor cells. These outcomes suggest the feasibility of grafting oligomeric FdU produgs in a covalent fashion into nanoscale platforms as a potential approach for cancer therapy.

Development of 225Ac-doped biocompatible nanoparticles for targeted alpha therapy

Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([225Ac]Ac3+). Encapsulation of [225Ac]Ac3+ within PLGA nanoparticles (Zave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [225Ac]Ac3+. Chelation of [225Ac]Ac3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([225Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [225Ac]AcBLPhen significantly increased the delivery of [225Ac]Ac3+ to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [225Ac]Ac3+ in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles.Graphical

Preparation and anti-tumor effect in hepatocellular carcinoma treatment of AS1411 aptamer-targeted polyphyllin II-loaded PLGA nanoparticles

Polyphyllin II (PPII) has been proven to have significant anti-liver cancer activity, but its application is limited by poor solubility, low bioavailability, and systemic toxicity caused by non-selectivity. To address the above problem, PPII was encapsulated into the Poly (lactic-co-glycolic acid) (PLGA) by precipitation method (PPII-NPs) for hepatocellular carcinoma treatment. Subsequently, Box–Behnken design (BBD) with three variables-three levels (33) was utilized to optimize the PPII-NPs formulation. Under optimal conditions, the drug loading of nanoparticles reached 7.29 ± 0.08% and encapsulation efficiency was 80.98 ± 1.63%. Furthermore, aptamer AS1411 was adopted to enhance the tumor-targeting ability of nanoparticles (Apt/PPII-NPs). The drug loading of Apt/PPII-NPs was 6.25 ± 0.26%, had a spherical shape with a rough surface, a particle size of 252.3 ± 3.6 nm, and showed good slow-release performance and stability. In vitro, assays showed that the targeted modified nanoparticles had significant tumor selectivity and exerted efficient anti-tumor effects by inducing tumor cell apoptosis via the mitochondrial apoptotic pathway and death‐receptor pathway. In vivo, anti-tumor evaluation further demonstrated Apt/PPII-NPs not only effectively inhibited the growth of tumors, but also reduced PPII damage to normal tissues. In summary, this report strongly illustrated the advantages of a targeted nanoparticle platform for providing a solution for the rational application of PPII and improving the therapeutic effect of hepatocellular carcinoma.

Retraction Note to: Anti-tumor effect of PEG-coated PLGA nanoparticles of febuxostat on A549 non-small cell lung cancer cells.

[This retracts the article DOI: 10.1007/s13205-020-2077-x.].

Formulation development of tazarotene-loaded PLGA nanoparticles for follicular delivery in the treatment of inflammatory skin diseases

Tazarotene is a widely prescribed topical retinoid for acne vulgaris and plaque psoriasis and is associated with skin irritation, dryness, flaking, and photosensitivity. In vitro permeation of tazarotene was studied across the dermatomed human and full-thickness porcine skin. The conversion of tazarotene to the active form tazarotenic acid was studied in various skin models. Tazarotene-loaded PLGA nanoparticles were prepared using the nanoprecipitation technique to target skin and hair follicles effectively. The effect of formulation and processing variables on nanoparticle properties, such as particle size and drug loading, was investigated. The optimized nanoparticle batches with particle size <500 µm were characterized further for FT-IR analysis, which indicated no interactions between tazarotene and PLGA. Scanning electron microscopy analysis showed uniform, spherical, and non-agglomerated nanoparticles. In vitro release study using a dialysis membrane indicated a sustained release of 40–70 % for different batches over 36 h, following a diffusion-based release mechanism based on the Higuchi model. In vitro permeation testing (IVPT) in full-thickness porcine skin showed significantly enhanced follicular and skin delivery from nanoparticles compared to solution. The presence of tazarotenic acid in the skin from tazarotene nanoparticles indicated the effectiveness of nanoparticle formulations in retaining bioconversion ability and targeting follicular delivery.

Exploring a hypothetical design of a nanoparticle-base cancer vaccine for the skin cancer melanoma

Melanoma is a skin cancer, in which cancer cells form in the melanocytes. It can occur anywhere on the skin but is hard to spot due to its only signs being a change in the way a specific mole or pigmented area looks. It is usually curable. Still, once it has bypassed stage IV, it can become fatal and deadly. The stages of melanoma depend on how thick the tumor is and whether it has broken through the skin. The most deadly is stage IV, in which the cancer has spread to numerous parts of the body, including but not limited to the lungs, liver, and brain. Studies have shown that the average 5-year survival rate for melanoma skin cancer is 94%; however, only 32% of people survive once the cancer has spread to distant parts of the body (The American Cancer Society et al., n.d.). Treatments for stage IV melanoma include surgery or radiation therapy. However, newer forms of immunotherapy and targeted drugs have shown to be more effective than chemotherapy. This paper will explore both the benefits and drawbacks of the immune checkpoint inhibitor atezolizumab and the BRAF inhibitor dabrafenib, both of which are FDA-approved. Furthermore, the paper will also explore the use of the PLGA nanoparticle in drug delivery as well as the possible future direction of this cancer treatment.

Enhancing the treatment of Staphylococcus aureus infections: A nanosystem with including dual antimicrobial peptide

The unique properties of nanoparticles (NPs) and their modification to selectively target infected tissues or specific pathogens could be an effective approach to revolutionize the treatment of infectious diseases. The objective of this study was to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with an antimicrobial peptide (HF-18) and decorated with an antimicrobial peptide (P6.2) for selective targeting against Staphylococcus aureus (S. aureus). Applying the Box-Behnken experimental design, HF-18 loaded PLGA nanoparticles were produced and optimized to have minimum particle size and polydispersity index (PDI) value by selecting primary water phase volume, organic phase volume and secondary water phase volume as independent parameters. Secondary water phase volume had the most significant effect on particle size and PDI. OPT-NP was more effective than HF-18 against most bacterial strains. The non-targeted (OPT-NP) and targeted (P6.2-OPT-NP) systems were shown to be biocompatible at levels that exhibited antibacterial activity. The P6.2-OPT-NP was predominantly taken up by S. aureus, while Escherichia coli (E. coli) used as a negative control showed minimal uptake. Furthermore, co-culture studies indicated that P6.2-OPT-NP was drastically uptake by S. aureus, while no internalized nanoparticles were visualized in fibroblast cells indicating active targeting of bacterial cells by P6.2-OPT-NP. Thus, these findings demonstrate the development of a formulation that selectively targets S. aureus, presenting promising prospects for future therapeutic applications.

Development, Characterization and In Vitro Gastrointestinal Release of PLGA Nanoparticles Loaded with Full-Spectrum Cannabis Extracts

Cannabinoids, such as ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are effective bioactive compounds that improve the quality of life of patients with certain chronic conditions. The copolymer poly(lactic-co-glycolic acid) (PLGA) has been used to encapsulate such compounds separately, providing pharmaceutical grade edible products with unique features. In this work, a variety of PLGA based nanoformulations that maintain the natural cannabinoid profile found in the plant (known as full-spectrum) are proposed and evaluated. Three different cannabis sources were used, representing the three most relevant cannabis chemotypes. PLGA nanocapsules loaded with different amounts of cannabinoids were prepared by nanoemulsion, and were then functionalized with three of the most common coating polymers: pectin, alginate and chitosan. In order to evaluate the suitability of the proposed formulations, all the synthesized nanocapsules were characterized, and their cannabinoid content, size, zeta-potential, morphology and in vitro bioaccessibility was determined. Regardless of the employed cannabis source, its load and the functionalization, high cannabinoid content PLGA nanocapsules with suitable particle size and zeta-potential were obtained. Study of nanocapsules’ morphology and in vitro release assays in gastro-intestinal media suggested that high cannabis source load may compromise the structure of nanocapsules and their release properties, and hence, the use of lower content of cannabis source is recommended.Graphical