Melanoma remains the most lethal form of skin cancer and most challenging to treat despite advances in the oncology field. Our work describes the utilization of nanotechnology to target melanoma locally in an attempt to provide an advanced and efficient quality of therapy. Amino-functionalized mesoporous silica nanoparticles (MSN-NH₂) were developed in situ through the utilization of anionic surfactant and different volumes of 3-aminopropyltriethoxysilane (APTES) as a co-structure directing agent (CSDA). Prepared particles were characterized for their morphology, particles size, 5-flurouracol (5-FU) and dexamethasone (DEX) loading capacity and release, skin penetration, and cytotoxicity in vitro in HT-144 melanoma cells. Results of transmission electron microscopy (TEM) and nitrogen adsorption–desorption isotherm showed that using different volumes of APTES during the functionalization process had an impact on the internal and external morphology of the particles, as well as particle size. However, changing the volume of APTES did not affect the diameter of formed mesochannels, which was about 4 nm. MSN-NH₂ showed a relatively high loading capacity of 5-FU (12.6 ± 5.5) and DEX (44.72 ± 4.21) when using drug: MSN-NH₂ ratios of 5:1 for both drugs. The release profile showed that around 83% of 5-FU and 21% of DEX were released over 48 h in pH 7.4. The skin permeability study revealed that enhancement ratio of 5-Fu and DEX using MSN-NH₂ were 4.67 and 5.68, respectively, relative to their free drugs counterparts. In addition, the accumulation of drugs in skin layers where melanoma cells usually reside were enhanced approximately 10 times with 5-FU and 5 times with DEX when delivering drugs using MSN-NH₂ compared to control. MSN-NH₂ alone was nontoxic to melanoma cells when incubated for 48 h in the range of 0 to 468 µg/mL. The combination of 5-FU MSN-NH₂ and DEX MSN-NH₂ showed significant increase in toxicity compared to their free dug counterparts and exhibited a synergetic effect as well as the ability to circumvent DEX induced 5-FU resistance in melanoma cells.

Bromocriptine mesylate (BM), primarily ergocryptine, is a dopamine agonist derived from ergot alkaloids. This study aimed to formulate chitosan (CS)-coated poly ε-caprolactone nanoparticles (PCL NPs) loaded with BM for direct targeting to the brain via the nasal route. PCL NPs were optimized using response surface methodology and a Box–Behnken factorial design. Independent formulation parameters for nanoparticle attributes, including PCL payload (A), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) concentration (B), and sonication time (C), were investigated. The dependent variables were nanoparticle size (Y1), zeta potential (Y2), entrapment efficiency (EE; Y3), and drug release rate (Y4). The optimal formulation for BM-PCL NPs was determined to be 50 mg PCL load, 0.0865% TPGS concentration, and 8 min sonication time, resulting in nanoparticles with a size of 296 ± 2.9 nm having a zeta potential of −16.2 ± 3.8 mV, an EE of 90.7 ± 1.9%, and a zero-order release rate of 2.6 ± 1.3%/min. The optimized BM-PCL NPs were then coated with CS at varying concentrations (0.25, 0.5, and 1%) to enhance their effect. The CS-PCL NPs exhibited different particle sizes and zeta potentials depending on the CS concentration used. The highest EE (88%) and drug load (DL; 5.5%) were observed for the optimized BM-CS-PCL NPs coated with 0.25% CS. The BM-CS-PCL NPs displayed a biphasic release pattern, with an initial rapid drug release lasting for 2 h, followed by a sustained release for up to 48 h. The 0.25% CS-coated BM-CS-PCL NPs showed a high level of permeation across the goat nasal mucosa, with reasonable mucoadhesive strength. These findings suggested that the optimized 0.25% CS-coated BM-CS-PCL NPs hold promise for successful nasal delivery, thereby improving the therapeutic efficacy of BM.

Glaucoma is a long-term eye disease associated with high intraocular pressure (IOP), which seriously damages the eyes, causing blindness. For successful therapy, potent drugs and delivery systems are required. Metoprolol (MT) is believed to help reduce elevated IOP. The paradigm of ocular therapeutics may be changed by the integration of chitosan-coated liposomes (CLPs) with thermosensitive in situ gel (ISG). Therefore, MT-CLPs were developed and characterized and compared to uncoated ones (MT-LPs). Furthermore, MT-LP- and MT-CLP-loaded ISGs were prepared and characterized in in vitro, ex vivo, and in vivo studies. MT-LPs and MT-CLPs displayed spherical shapes with nanosize range, reasonable EE%, and significant bioadhesion. The zeta potential changed from negative to positive after CS coating. The extended in vitro drug release of MT-CLPs showed significant mucin mucoadhesion. The formed ISGs were homogeneous with a pH range of 7.34 to 7.08 and a rapid sol–gel transition at physiological temperature. MT-ISG1 (MT-LP) and MT-ISG2 (MT-CLPs-0.5) could increase ocular permeability by 2-fold and 4.4-fold compared to MT-ISG (pure MT). MT-ISG2 demonstrated significantly reduced IOP in rabbits without causing any irritation. In conclusion, MT-ISG2 markedly enhanced corneal permeability and reduced IOP. They would be promising carriers for MT for glaucoma management.

The current study aimed to develop and evaluate a sustained-release transdermal Glipizide (GLP) film to overcome its oral administration problems. Chitosan (CS)-coated deformable liposomes (DLs) were utilized to enhance the drug transdermal delivery. The formulations were characterized in terms of particle size, zeta potential, entrapment efficiency (EE%), vesicle deformability, morphology, stability, and in vitro release. Transdermal films of chosen formulations were prepared by the solvent casting technique, and an ex vivo study throughout rat skin was also performed. Moreover, a pharmacokinetics (PK) study was carried out and blood glucose levels were estimated. All the liposomes were in the nanometer range and a high EE% was obtained from DLs compared to conventional liposomes (CL). The prepared formulations showed a high stability and the DLs exhibited a high deformability compared to CL. The in vitro release study confirmed the sustained release of GLP from both CL and DL and a more pronounced sustained release of GLP was detected after coating with CS. Moreover, GLP was shown to efficiently permeate through the rat skin from transdermal films by an ex vivo permeation test. The transdermal films showed a promising PK profile in the rat as compared with oral GLP. Most importantly, GLP-CS-DL1 demonstrated a higher hypoglycemic effect, confirming the possibility of systemic action by the local topical delivery of GLP.

Aloe perryi (ALP) is an herb that has several biological activities such as antioxidant, antibacterial, and antitumor effects and is frequently used to treat a wide range of illnesses. The activity of many compounds is augmented by loading them in nanocarriers. In this study, ALP-loaded nanosystems were developed to improve their biological activity. Among different nanocarriers, solid lipid nanoparticles (ALP-SLNs), chitosan nanoparticles (ALP-CSNPs), and CS-coated SLNs (C-ALP-SLNs) were explored. The particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and release profile were evaluated. Scanning electron microscopy was used to see the nanoparticles’ morphology. Moreover, the possible biological properties of ALP were assessed and evaluated. ALP extract contained 187 mg GAE/g extract and 33 mg QE/g extract in terms of total phenolic and flavonoid content, respectively. The ALP-SLNs-F1 and ALP-SLNs-F2 showed particle sizes of 168.7 ± 3.1 and 138.4 ± 9.5 nm and the zeta potential values of −12.4 ± 0.6, and −15.8 ± 2.4 mV, respectively. However, C-ALP-SLNs-F1 and C-ALP-SLNs-F2 had particle sizes of 185.3 ± 5.5 and 173.6 ± 11.3 nm with zeta potential values of 11.3 ± 1.4 and 13.6 ± 1.1 mV, respectively. The particle size and zeta potential of ALP-CSNPs were 214.8 ± 6.6 nm and 27.8 ± 3.4 mV, respectively. All nanoparticles exhibited PDI < 0.3, indicating homogenous dispersions. The obtained formulations had EE% and DL% in the ranges of 65–82% and 2.8–5.2%, respectively. After 48 h, the in vitro ALP release rates from ALP-SLNs-F1, ALP-SLNs-F2, C-ALP-SLNs-F1, C-ALP-SLNs-F2, and ALP-CSNPs were 86%, 91%, 78%, 84%, and 74%, respectively. They were relatively stable with a minor particle size increase after one month of storage. C-ALP-SLNs-F2 exhibited the greatest antioxidant activity against DPPH radicals at 73.27%. C-ALP-SLNs-F2 demonstrated higher antibacterial activity based on MIC values of 25, 50, and 50 µg/mL for P. aeruginosa, S. aureus, and E. coli, respectively. In addition, C-ALP-SLNs-F2 showed potential anticancer activity against A549, LoVo, and MCF-7 cell lines with IC50 values of 11.42 ± 1.16, 16.97 ± 1.93, and 8.25 ± 0.44, respectively. The results indicate that C-ALP-SLNs-F2 may be promising nanocarriers for enhancing ALP-based medicines.