Current Drug Delivery - Online First

Gemcitabine (Gem) is a well-known antineoplastic drug used to treat several solid tumors. The clinical application of Gem is hampered owing to its non-selectivity, short half-life, and drug resistance, which, therefore, necessitate the development of a suitable novel formulation that can selectively target cancer sites.

In present work, Gem-loaded bovine serum albumin nanoparticles (Gem-BSANPs) have been prepared by using the desolvation cross-linking method and coated with hyaluronic acid (HA-Gem-BSANPs) to target the CD44 receptor which overexpressed on several solid tumors. The developed NPs were characterized by particle size, zeta potential, Transmission Electron Microscopy (TEM), and Differential Scanning Calorimetry (DSC). Further anticancer activity of the developed formulation was evaluated against A549 and MCF-7 cells and explored mode of action studies.

The mean particle size and zeta potential of HA-Gem-BSANPs were observed as 144.7±5.67 nm and -45.72±3.24 mV, respectively. The TEM analysis also corroborated the particle size and shape, while thermal analysis (DSC) indicated that Gem was entrapped into NPs in an amorphous form. The nucleoside transport inhibition assay demonstrated that the NPs do not depend on transporters for cellular internalization, and hence, resistance development in cells is less expected against this formulation. HA-Gem-BSANPs exhibited higher cytotoxicity and apoptosis on both the tested cell lines. However, better cell-killing ability and mitochondrial membrane potential loss were observed against A549 due to CD44 expression.

The present work demonstrated that HA-Gem-BSANPs could be a potential strategy to improve Gem's therapeutic efficacy by selectively targeting the tumor site.

Hot-melt Pressure-sensitive Adhesives (HMPSA) are eco-friendly pressure-sensitive adhesives, with the potential of being used as substrates for transdermal patches. However, due to the low hydrophilicity of HMPSA, the application is limited in the field of Traditional Chinese Medicine (TCM) plasters.

Three modified HMPSA were prepared with acrylic resin EPO, acrylic resin RL100, and Polyvinylpyrrolidone (PVP) as the modifying materials. The physical compatibility between HMPSA and the modifying materials was investigated through in vitro release performance, viscosity, softening point, cohesion, and fluidity, so as to determine the most effective modifying material. The impact of the modified HMPSA on the release properties of different TCM ingredients was elucidated by the performance of water absorption and contact angle behavior.

With the addition of the modifying materials, both the viscosity and the softening point of HMPSA were improved, with the flowability reduced and the cohesion maintained. The morphological and structural changes reflected the physical compatibility between HMPSA and the three modifying materials. According to the results of in vitro release experiments, PVP effectively improved the release performance of paeoniflorin, ephedrine hydrochloride, and cinnamaldehyde in HMPSA, with no significant impact on the release performance of eugenol. The changes in the drug release performance of HMPSA may be attributed to the improved hydrophilicity of HMPSA after physical modification.

The compatibility and the drug release performance of HMPSA were effectively enhanced after the addition of the modifying materials by the physical blending technique. Among the three modifying materials, PVP has been found to be an ideal modifying material for HMPSA in the field of TCM plasters due to its effects on drug release performance.

DSPE-mPEG2000 is a phospholipid and polyethylene glycol conjugate used in various biomedical applications, including drug delivery, gene transfection, and vaccine delivery. Due to the hydrophilic and hydrophobic properties of DSPE-mPEG2000, it can serve as a drug carrier, encapsulating drugs in liposomes to enhance stability and efficacy.

In this study, long-circulating podophyllotoxin liposomes (Lc-PTOX-Lps) were prepared using DSPE-mPEG2000 as a modifying material and evaluated for their pharmacokinetics and anticancer activity.

Lc-PTOX-Lps had an encapsulation rate of 87.11±1.77%, an average particle size of 168.91±7.07 nm, a polydispersity index (PDI) of 0.19±0.04, and a zeta potential of -24.37±0.36 mV. In vitro release studies showed that Lc-PTOX-Lps exhibited a significant slow-release effect. The long-circulating liposomes demonstrated better stability compared to normal liposomes and exhibited a significant slow-release profile. Pharmacokinetic studies indicated that Lc-PTOX-Lps had a prolonged half-life, reduced in vivo clearance, and improved bioavailability. Additionally, Lc-PTOX-Lps exhibited better anticancer effects on MCF-7 cells and lower toxicity to normal cells compared to PTOX.

Lc-PTOX-Lps were synthesized using a simple and effective method, and Lc-PTOX-Lps are promising anticancer agents.

Fungal keratitis (mycotic keratitis) is an eye infection in which the cornea is infected by fungi and such fungal keratitis management can be effectively possible by ocular administration of antifungal drugs.

The main objectives of the present research were to develop and evaluate fluconazole-loaded transfersomal hydrogels for ocular delivery in the effective management of fungal keratitis.

A 2³ factorial design-based approach was used for statistical optimization, where (A) the ratio of lipid to edge activators, (B) the amount of hyaluronic acid (% HA), and (C) the ratio of edge activators (sodium deoxycholate to Span 80) were taken as three factors. The average vesicle diameter (Z, nm) of transfersomes was taken as a response. Further, fluconazole-loaded transfersomes (FTO) were incorporated into 1% Carbopol 940-based hydrogel (OF1) and 2% HMPC K4M-based hydrogel (OF2) containing D-panthenol (5% w/w).

The optimal variable setting for the optimized formulations of FTO was (A) = 9.15, (B) = 0.30%, and (C) = 3.00. FTO exhibited 66.39 nm Z, 0.247 polydispersity index, – 33.10 mV zeta potential, and 65.38 ± 1.77% DEE, and desirable elasticity. TEM image of FTO demonstrated a unilamellar vesicular structure. The ex vivo ocular permeation of fluconazole from transfersomal hydrogels was sustained over 24 h. All the transfersomal hydrogels showed good bioadhesion and excellent antifungal activity with respect to the zone of inhibition against Candida albicans than Aspergillus fumigates, in vitro. HET-CAM study results demonstrated that both the hydrogels were non-irritant and safe for ocular. Short-term physical stability study suggested the stability of the developed formulation.

The current research demonstrated a new way to enhance the ocular penetration of fluconazole via transfersomal hydrogel formulations for ocular delivery in the effective management of fungal keratitis.

The spread of tumors (48% in men and 51% in women), as well as the protection of malignant tumors by stromal cells and complex blood vessels, pose significant challenges to drug delivery to tumors. Modern chemotherapy, on the other hand, addresses tumor growth suppression by at least 60% through versatile formulation systems and numerous modifications to drug delivery systems. The renewable and naturally occurring polymers present invariably in all living cells form the fundamental foundation for most anticancer drug development. The review aims to discuss in detail the preparations of polysaccharide, lipid, and protein-based drug-loading vehicles for the targeted delivery of prominent anticancer drugs. It also provides an explanation of drug distribution in blood (cumulative releases of nearly 80% drug) and drug accumulation at tumor sites (1–5 mg/kg) due to enhanced permeability and retention (EPR).

Specific delivery examples for treating colorectal and breast carcinomas have been presented to distinguish the varied drug administration, bioavailability, and tumor internalization mechanisms between sugar, fatty acid, and amino acid polymers. Current therapy possibilities based on cutting-edge literature are provided, along with drug delivery systems tailored to tumor location and invasive properties.

The unique combinations of the three natural polymers provide unparalleled solutions to minimize the toxicity (<20% drug release) of the chemotherapeutic drugs on normal tissues. Moreover, the development of a consolidated drug delivery system has contributed to a substantial reduction (dose reduction from 10.43 µM to 1.9 µM) in the undesirable consequences of higher dosages of chemotherapeutic drugs.

The review extensively covers safe chemotherapeutic systems with significant advantages (tumor volume shrinkage of 4T1 cells from 1000 mm³ to 200 mm³) in clinical applications of carcinoma treatments using natural polymers.

The last strategy in targeted drug delivery systems is to deliver the anticancer drug to the tumor tissue to increase its therapeutic effect and minimize its undesirable side effects. In line with this goal in this research, the redox/pH-responsive disulfide magnetic nanocarriers based on PF127-NH2/L-cysteine-CM-β-CD-FA were synthesized and evaluated in a doxorubicin delivery system.

We effectively surrounded Fe3O4 nanoparticles with SiO2 using the sol-gel method, and then confidently coated them with oleic acid on Fe3O4@SiO2 nanoparticles.. In another reaction, a PF127-NH2/L-cysteine-CM-β-CD-FA was synthesized. The process involved modifying pluronic F127 (PF 127) with maleic anhydride and aminating it to form PF127-NH2. The obtained PF127-NH2 was attached to L-cysteine, followed by condensing with carboxymethyl-β-cyclodextrin and then functionalized by folic acid. Finally, PF127-NH2/L-cysteine-CM-β-CD-FA was coated on the surface of magnetic nanoparticles, and the resulting PF127-NH2/L-cysteine-CM-β-CD-FA was disulfidated to form the final nanocarrier network, which was abbreviated as LCMNPs-SS. The doxorubicin was used as a model drug and loaded into the LCMNPs-SS nanocarrier.

The LCMNPs-SS nanocarrier exhibited excellent properties for controlled release, with a well-defined release rate, a controllable level by an external magnet, and adjusting by DL-dithiothreitol concentration. The LCMNPs-SS nanocarrier could also break apart when exposed to an oxidant or a change in pH. This meant that the drug release could be fine-tuned in response to temperature, pH, or more than one stimulus.

These drug-carrying systems are valuable in reducing the dose of doxorubicin. High internalization of the synthesized LCMNPs-SS caused sped cellular uptake.