The electrospray (ES) technique has proven to be an effective and a versatile approach for crafting drug delivery carriers with diverse dimensions, multiple layers, and varying morphologies. Achieving the desired particle properties necessitates careful optimization of various experimental parameters. This review delves into the most prevalent ES system configurations employed for this purpose, such as monoaxial, coaxial, triaxial, and multi-needle setups with solid or liquid collector. In addition, this work underscores the significance of ES in drug delivery carriers and its remarkable ability to encapsulate a wide spectrum of therapeutic agents, including drugs, nucleic acids, proteins, genes and cells. Depth examination of the critical parameters governing the ES process, including the choice of polymer, surface tension, voltage settings, needle size, flow rate, collector types, and the collector distance was conducted with highlighting on their implications on particle characteristics, encompassing morphology, size distribution, and drug encapsulation efficiency. These insights illuminate ES's adaptability in customizing drug delivery systems. To conclude, this review discusses ES process optimization strategies, advantages, limitations and future directions, providing valuable guidance for researchers and practitioners navigating the dynamic landscape of modern drug delivery systems.
As per the WHO, colorectal cancer (CRC) caused around 935,173 deaths worldwide in 2020 in both sexes and at all ages. The available anticancer therapies including chemotherapy, radiotherapy and anticancer drugs are all associated with limited therapeutic efficacy, adverse effects and low chances. This has urged to emerge several novel therapeutic agents as potential therapies for CRC including synthetic and natural materials. Orally administrable and targeted drug delivery systems are attractive strategies for CRC therapy as they minimize the side effects, enhance the efficacy of anticancer drugs. Nevertheless, oral drug delivery till today faces several challenges like poor drug solubility, stability, and permeability. Various oral nano-based approaches and targeted drug delivery systems have been developed recently, as a result of the ability of nanoparticles to control the release of the encapsulant, drug targeting and reduce the number of dosages administered. The unique physicochemical properties of chitosan polymer assist to overcome oral drug delivery barriers and target the colon tumour cells. Chitosan-based nanocarriers offered additional improvements by enhancing the stability, targeting and bioavailability of several anti-colorectal cancer agents. Modified chitosan derivatives also facilitated CRC targeting through strengthening the protection of encapsulant against acidic and enzyme degradation of gastrointestinal track (GIT). This review aims to provide an overview of CRC pathology, therapy and the barriers against oral drug delivery. It also emphasizes the role of nanotechnology in oral drug targeted delivery system and the growing interest towards chitosan and its derivatives. The present review summarizes the relevant works to date that have studied the potential applications of chitosan-based nanocarrier towards CRC treatment.
Colon-targeted delivery offers several benefits for oral protein delivery, such as low proteolytic enzyme activity, a natural pH environment, and extended residence time, which improve the bioavailability of the encapsulated protein. Therefore, we hypothesize that developing a novel colonic nanocarrier system, featuring modified chitosan that is soluble at physiological pH and coated with a colon-degradable polymer, will provide an effective delivery system for oral insulin. This study aims to synthesize insulin-loaded pectin-trimethyl chitosan nanoparticles (Ins-P-TMC-NPs) as an oral insulin delivery system and to evaluate its efficacy both in vitro and in vivo. N-trimethyl chitosan (TMC), synthesized via a methylation method, was used to prepare insulin-TMC nanoparticles coated with pectin via the ionic gelation method. The nanoparticles were characterized for their physicochemical properties, cumulative release profile, and surface morphology. The in vitro biological cytotoxicity and cellular uptake of the nanoparticles were evaluated against HT-29 cells. The in vivo blood glucose-lowering effect and histological toxicity were assessed in diabetic male Sprague-Dawley rats. The results showed that Ins-P-TMC-NPs were spherical, with an average size of 379.40 ± 40.26 nm, a polydispersity index of 24.10 ± 1.03 %, a zeta potential of +17.20 ± 0.52 mV, and a loading efficiency of 83.21 ± 1.23 %. Compared to uncoated TMC nanoparticles, Ins-P-TMC-NPs reduced insulin loss in simulated gastrointestinal fluid by approximately 67.23 ± 0.97 % and provided controlled insulin release in simulated colonic fluid. In vitro bioactivity studies revealed that Ins-P-TMC-NPs were non-toxic, with cell viability of 91.12 ± 0.91 % after 24 h of treatment, and exhibited high cellular uptake in the HT-29 cell line with a fluorescence intensity of 37.80 ± 2.40 after 4 h of incubation. Furthermore, the in vivo study demonstrated a sustained reduction in blood glucose levels after oral administration of Ins-P-TMC-NPs, peaking after 8 h with a blood glucose reduction of 87 ± 1.03 %. Histological sections showed no signs of toxicity when compared to those of healthy rats. Overall, the developed colon-targeted oral insulin delivery system exhibits strong potential as a candidate for effective oral insulin administration.