Biophysical analysis on molecular interactions between chitosan-coated sinapic acid loaded liposomes and mucin.

BACKGROUND: The mucus biomembrane is a primary barrier in delivering drugs to the brain via intranasal delivery. The negatively charged nanoformulations suffer from poor mucoadhesive ability and less retention time in the nasal cavity, which limits further therapeutic efficacy. The positively charged chitosan coating on liposomes may overcome the above issues. Hence, understanding the molecular interactions between the chitosan-coated liposomes and mucin is essential for developing an effective drug delivery system. METHODS: The molecular interactions of mucin with sinapic acid-loaded liposomes (SA-LPs) and mucin with chitosan-coated sinapic acid-loaded liposomes (SA-CH-LPs) were assessed using different biophysical instrumental analyses by interpreting the UV-Vis spectra and observing the particle size, polydispersity index, surface charge, and rheological behavior. RESULTS: The mucin interaction with SA-CH-LPs showed increased viscosity as compared to SA-LPs with mucin. Moreover, the mucin interaction with SA-CH-LPs showed stronger mucoadhesive properties as compared to SA-LPs with mucin. The electrostatic interaction between positively charged SA-CH-LPs and negatively charged mucin was responsible for the enhanced mucoadhesive property. CONCLUSION: The positively charged SA-CH-LPs highly interact with mucin as compared to negatively charged SA-LPs. The mucoadhesive property of SA-CH-LPs could improve the retention of SA in the nasal cavity as compared to SA-LPs. These findings emphasize the importance of chitosan in modulating the mucoadhesive behavior of liposomes. GENERAL SIGNIFICANCE: Overall, this study helps to understand the molecular interactions and mucoadhesive nature of the chitosan-coated liposomes with mucin, which is essential for biological activity in the physiological environment.

Investigation of ROS generating capacity of curcumin-loaded liposomes and its in vitro cytotoxicity on MCF-7 cell lines using photodynamic therapy.

Photodynamic therapy (PDT) is highly efficient in eradicating targetlesions by using photosensitizers (PS) triggered by external light energy. Nanotechnology may help increase the solubility and effective delivery of PS towards improving its efficacy. Curcumin (Cur) was used as a natural PS for PDT in the present work. Briefly, curcumin was encapsulated in liposomes (LPs) using the thin film hydration method and optimized using the QbD approach through the Box-Behnken Design (BBD) to optimize the responses like entrapment efficiency and drug loading with a smaller vesicle size. The in vitro release studies performed using a dialysis bag (MWCO 12 KDa) suggested a sustained release of the Cur over 72 h in pH 7.4 PBS following the Weibull drug release kinetics. In addition, the ROS generating capabilities upon application of blue light (460 nm) and resulting cytotoxicity were evaluated in MCF-7 cell lines. The Cur-loaded liposome exhibited significant ROS generation and cytotoxicity to the cancer cells than free curcumin. Thus, the Cur-loaded liposomes could be used to treat breast cancer with photodynamic therapy.

PCL-PEG copolymer based injectable thermosensitive hydrogels.

A number of stimuli-responsive-based hydrogels has been widely explored in biomedical applications in the last few decades because of their excellent biodegradability and biocompatibility. The development of synthetic chemistry and materials science leads to the emergence of in situ stimuli-responsive hydrogels. In this regard, several synthetic and natural polymers have been synthesized and utilized to prepare temperature-sensitive in situ forming hydrogels. This could be best used via injections as temperature stimulus could trigger in situ hydrogels gelation and swelling behaviors. There are many smart polymers available for the formulation of the in situ based thermoresponsive injectable hydrogel. Among these, poly (ε-caprolactone) (PCL) polymer has been recognized and approved by the FDA for numerous biomedical applications. More specifically, the PCL is coupled with polyethylene glycol (PEG) to obtain amphiphilic thermosensitive "smart" copolymers (PCL-PEG), to form rapid and reversible physical gelation behavior. However, the chemical structure of the copolymer is a critical aspect in determining water solubility, thermo-gelation behavior, drug release rate, degradation rate, and the possibility to deliver a diverse range of drugs. In this review, we have highlighted the typical PCL-PEG-based thermosensitive injectable hydrogels progress in the last decade for tissue engineering and localized drug delivery applications to treat various diseases. Additionally, the impact of molecular weight of PCL-PEG upon gelling behavior has also been critically highlighted for optimum hydrogels properties for potential pharmaceutical and biomedical applications.

Nose-to-brain drug delivery for the treatment of Alzheimer's disease: current advancements and challenges.

INTRODUCTION: The irreversible destruction of neurons, progressive loss of memory and cognitive behavior, high cost of therapy, and impact on society, desire a better, effective, and affordable treatment of AD. The nose-to-brain delivery approach holds great potential to access the brain without any hindrance of BBB and results in higher bioavailability and thus better therapeutic efficacy of anti-AD drugs. AREAS COVERED: The present review article highlights the current facts and worldwide statistics of AD and its detailed etiology. This is followed by barriers to brain delivery, nose-to-brain delivery, their limitations, and amalgamation with various novel carrier systems. We have emphasized recent advancements in nose-to-brain delivery using mucoadhesive, stimuli-responsive carriers, polymeric nanoparticles, lipid nanoparticles, and protein/peptide delivery for treatment of AD. EXPERT OPINION: The available therapies are symptomatic and mitigate the symptoms of AD at the initial stages. In lieu of this, nose-to-brain delivery has the ability to overcome these limitations and increase drug bioavailability in the brain. Various novel strategies including stimuli-responsive systems, nanoparticles, etc. enhance the nasal permeation, protect the drug, and enhance its therapeutic potency. However, successful preclinical data do not assure the clinical success of the therapy, and hence exhaustive clinical investigations are needed to make the therapy available for patients.