Search

Centella asiatica, a medicinal herb used for wound healing, has a limited effect when delivered as an ointment. Centella asiatica's active component asiatic acid (AA) increases extracellular matrix development and reduces inflammation but cannot penetrate the stratum corneum to access deeper skin layers. To bypass the stratum corneum, we formulated two types of AA-loaded microneedle arrays. We fabricated, characterised and optimised a dissolving array made from chitosan and PVA and a hydrogel array made from chitosan and PVP. Both needles were strong and long enough to pierce the epidermis without breaking. Both were biocompatible with keratinocytes and fibroblasts (>75% viability at 100% concentration) and showed a sustained drug release over 48 h. The hydrogel microneedle released more AA (52.2%) than the dissolving formulation (26.4%); thus, we evaluated them in an excisional rat model. The hydrogel microneedle arrays significantly increased the rate of wound closure compared to the control. This research has shown that the chitosan-PVA hydrogel microneedles could penetrate the epidermis, effectively release AA, and increase the wound closure rate. This AA-loaded delivery system shows promise as a natural treatment for wound healing and may be applied to other bioactive compounds with similar physiochemical properties in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Gemcitabine is a nucleoside analogue effective against a number of cancers. However, the full potential of this drug has not been realised, in part due to low oral bioavailability and frequent dosing requirements. This study reports the synthesis, in-vitro, ex-vivo and in-vivo evaluation of trimethyl chitosan (TMC) - CSKSSDYQC (CSK) peptide conjugates capable of enhancing the oral bioavailability of gemcitabine due to the ability to target intestinal goblet cells and promote intestinal cellular uptake. TMC was synthesized by a novel two-step methylation method to improve quanternization and yield. The CSK-TMC conjugates were prepared by ionic gelation to achieve particles sized at 173.6 ± 6.8 nm, zeta potential of +18.5 ± 0.2 mV and entrapment efficiency of 66.4 ± 0.1%, capable of sustained drug release. By encapsulating gemcitabine into CSK-TMC conjugates, an increased amount of drug permeated through porcine intestinal epithelial membranes compared with the unconjugated TMC nanoparticles (NPs). The rate of cellular uptake of drug loaded conjugates into HT29-MTX-E12 intestinal goblet cells, was time- and concentration-dependant. The conjugates underwent active transport associated with adsorptive mediated, clathrin and caveolae mediated endocytosis. In cellular transport studies, drug loaded conjugates had greater drug transport capability compared with drug solution and TMC NPs over the co-cultured Caco-2/HT29-MTX-E12 cell monolayer. The drug loaded conjugates exhibited electrostatic interaction with the intestinal epithelial cells. Both P-glycoprotein (P-gp) and multiple resistance protein-2 (MRP2) efflux affected the cellular transport of the conjugates. Importantly, during the pharmacokinetic studies, the orally administrated drug loaded into TMC NPs showed an improved oral bioavailability of 54.0%, compared with gemcitabine solution of 9.9%. Notable, the CSK-TMC conjugates further improved oral bioavailability to 60.1% and reduced the tumour growth rate in a BALB/c nude mouse model, with a 5.1-fold and 3.3-fold reduction compare with the non-treated group and gemcitabine solution group. Furthermore, no major evidence of toxicity was discernible on histologic studies of selected organs. In conclusion, the presented CSK-TMC conjugates and TMC nanoparticles both significantly improve the oral bioavailability of gemcitabine and have the potential for the treatment of breast cancer., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study aimed at improving the systemic bioavailability of propranolol-HCl by the design of transdermal drug delivery system based on chitosan nanoparticles dispersed into gels. Chitosan nanoparticles were prepared by ionic gelation technique using tripolyphosphate (TPP) as a cross-linking agent. Characterization of the nanoparticles was focused on particle size, zeta potential, surface texture and morphology, and drug encapsulation efficiency. The prepared freeze dried chitosan nanoparticles were dispersed into gels made of poloxamer and carbopol and the rheological behaviour and the adhesiveness of the gels were investigated. The results showed that smallest propranolol loaded chitosan nanoparticles were achieved with 0.2% chitosan and 0.05% TPP. Nanoparticles were stable in suspension with a zeta potential (ZP) above ±30mV to prevent aggregation of the colloid. Zeta potential was found to increase with increasing chitosan concentration due to its cationic nature. At least 70% of entrapment efficiency and drug loading were achieved for all prepared nanoparticles. When chitosan nanoparticles dispersed into gel consisting of poloxamer and carbopol, the resultant formulation exhibited thixotropic behaviour with a prolonged drug release properties as shown by the permeation studies through pig ear skin. Our study demonstrated that the designed nanoparticles-gel transdermal delivery system has a potential to improve the systemic bioavailability and the therapeutic efficacy of propranolol-HCl., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A critical problem associated with delivery of bovine lactoferrin (bLf) by the oral route is low bioavailability, which is derived from the enzymatic degradation in the gastrointestinal tract and poor permeation across the intestinal epitheliums. Particulate carrier systems have been identified to protect bLf against proteolysis via encapsulation. This study aimed to evaluate the physico-chemical stability of bLf-loaded liposomes and solid lipid particles (SLPs) modified by pectin and chitosan when exposed to various stress conditions. Transmission electron microscopy results showed liposomes and SLPs had a classic shell-core structure with polymer layers surrounded on surface, but the structure appeared to be partially broken after digestion in simulated intestinal fluid (SIF). Although HPLC and sodium dodecyl sulphate-polyacrylamide gel electrophoresis methods qualitatively and quantitatively described either liposomes or SLPs could retain intact bLf against proteolysis in SIF to some extent, all liposome formulations showed rapid rate of lipolysis mediated by pancreatic enzymes. On the other hand, all SLP formulations showed higher heat resistance and greater electrolyte tolerance compared to liposome formulations. After 180 days storage time, liposome-loaded bLf was completely degraded, whereas almost 30% of intact bLf still remained in SLP formulations. Overall, SLPs are considered as primary choice for oral bLf delivery., (© 2015 John Wiley & Sons A/S.)

N -trimethyl chitosan (TMC) is a multifunctional polymer that can be used in various nanoparticle forms in the pharmaceutical, nutraceutical and biomedical fields. In this study, TMC was used as a mucoadhesive adjuvant to enhance the oral bioavailability and hence antitumour effects of gemcitabine formulated into nanocomplexes composed of poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) conjugated with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). A central composite design was applied to achieve the optimal formulation. Cellular uptake and drug transportation studies revealed the nanocomplexes permeate over the intestinal cells via adsorptive-mediated and caveolae-mediated endocytosis. Pharmacokinetic studies demonstrated the oral drug bioavailability of the nanocomplexes was increased 5.1-fold compared with drug solution. In pharmacodynamic studies, the formulation reduced tumour size 3.1-fold compared with the drug solution. The data demonstrates that TMC modified nanocomplexes can enhance gemcitabine oral bioavailability and promote the anticancer efficacy. [Display omitted] • Synthesized TMC modifies the PLGA-TPGS nanocomplexes to enhance oral absorption. • The central composite design model was applied to obtain the optimal formulation. • The drug release mechanism is governed by anomalous diffusion. • TMC led cell uptake of particles by adsorptive and caveolae-mediated endocytosis. • The carrier greatly enhanced oral drug bioavailability and inhibited tumour growth. [ABSTRACT FROM AUTHOR]