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The rapid increase in the number of stimuli-responsive polymers, also known as smart polymers, has significantly advanced their applications in various fields. These polymers can respond to multiple stimuli, such as temperature, pH, solvent, ionic strength, light, and electrical and magnetic fields, making them highly valuable in both the academic and industrial sectors. Recent studies have focused on developing hydrogels with self-healing properties that can autonomously recover their structural integrity and mechanical properties after damage. These hydrogels, formed through dynamic covalent reactions, exhibit superior biocompatibility, mechanical strength, and responsiveness to stimuli, particularly pH changes. However, conventional hydrogels are limited by their weak and brittle nature. To address this, ionizable moieties within polyelectrolytes can be tuned to create ionically cross-linked hydrogels, leveraging natural polymers such as alginate, chitosan, hyaluronic acid, and cellulose. The integration of ionic liquids into these hydrogels enhances their mechanical properties and conductivity, positioning them as significant self-healing agents. This review focuses on the emerging field of stimuli-responsive ionic-based hydrogels and explores their potential in dermal applications and tissue engineering.

Aim: To develop a glycerol modified liposomes to effectively deliver active agents into posterior segment of the eye for the management of posterior uveitis., Materials and Methods: The modified liposome enhanced with glycerol as an edge activator was fabricated using a 3 2 experimental design with independent variables being soya lecithin (mg) (X 1 ) and glycerol (%) (X 2 ) and vesicle size (nm) (Y 1 ), deformability index (%) (Y 2 ), and entrapment efficiency (%) (Y 3 ) as dependent variable with improve permeability and entrapment efficacy. These modified liposomes were then integrated into pHEMA-based contact lenses via free radical polymerization using different monomer mixture, co-polymer, crosslinker, and photo-initiator to extend drug release., Results and Conclusions: Nano-vesicles resulted in size and deformability index of 200.5 ± 15 nm and 11.58, respectively, with entrapment efficiency of 80.98% of the drug. Moreover, the optimized lenses demonstrated 71%) of swelling and transmittance of 87%). In addition, in vitro release of active component from the therapeutic contact lens demonstrated sustained drug release over 24 h. Whereas ex vivo studies displayed a 5-fold increase in drug permeation, compared to tested conventional eye drops. The results suggested that glycerosomes-loaded contact lens can be a promising alternative for regulated delivery of dexamethasone sodium phosphate in the management of posterior uveitis.

The dermal delivery of peptide therapeutics that are of high molecular weight is a challenge. Cyclosporine A (CsA) is a cyclic undecapeptide with poor aqueous solubility and high molecular weight (1202 Da) indicated for psoriasis. The objective of the study was to evaluate the effect of ionic liquids mixed with the Pluronic F127 matrix in skin permeation of CsA and its efficacy in psoriasis treatment. Choline and geranic acid (CAGE) ionic liquids in a 1:2 molar ratio were mixed with Pluronic F127 (22.7%) and PEG 400 (45%) to prepare an organogel formulation. The CsA-loaded CAGE (CsA-CAGE) and CAGE-Pluronic F127 gels (CsA-CAGE-P gel) were characterized for physical and rheological characteristics. The skin transport studies showed that free CsA did not permeate across the excised porcine skin after 48 h. The amount of CsA permeated across the oleic acid (0.25% v/v) and palmitic acid (0.25% w/v) cotreated skin was found to be 244 ± 4 and 1236 ± 17 μg/cm 2 , respectively. The application of CsA-CAGE and CsA-CAGE-P gel enhanced CsA flux by 110- and 135-fold, respectively, compared with the control. The thermal analysis and biophysical studies changed the barrier property of the skin significantly ( p < 0.05) after incubation with CAGE and CAGE-P gel. The pharmacokinetic studies in the rat model showed that topical application of CsA-CAGE-P gel provided 2.6- and 1.9-fold greater C max and AUC 0 - t , respectively, compared to the control group. In vitro - in vivo level A correlations were established with R 2 values of 0.991 and 0.992 for both linear and polynomial equations for the CsA-CAGE-P gel formulation using the Wagner - Nelson method. The topical application of CsA-CAGE-P gel (10 mg/kg) on an imiquimod-induced plaque psoriatic model reduced the area of the psoriasis and severity index (PASI) score significantly for erythema and scaling, reversing the changes to skin thickness, blood flow rate, and transepidermal water loss. Together, CAGE-Pluronic F127 organogel was developed as an effective topical formulation for the local and systemic delivery of CsA for the treatment of psoriasis., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The development of a long-acting orally administered dosage form is a challenge. Here, we report development of a multi-layered mucoadhesive gastric patch that could deliver entrapped chemotherapeutic agent for eight days after oral administration. The multi-layered patch was designed to contain core layer, mucoadhesive layer and backing layer. The core layer contained the model chemotherapeutic agent, regorafenib. The mucoadhesive layer made of chitosan-hydrocaffeic acid conjugate showed greatest mucoadhesion strength of 18.1 ± 0.78 kPa in freshly excised rat gastric mucosa. The backing layer made of hydrophobic polycaprolactone-polydimethylsiloxane composite showed the contact angle of 120 ± 4.7° after placement of water drop. The entrapped regorafenib predominantly released from the mucoadhesive-side of the patch into simulated gastric fluid and showed a zero-order release profile. The patches were found to be stable for desired characteristics for up to 3 months in long term storage conditions. The pharmacokinetic studies in rat model revealed constant plasma concentration of regorafenib sustained for 8 days after oral administration of gastric patch. The gastric tissue where the patch adhered for 8 days did not show any significant histological changes compared with the normal gastric tissue. The oral administration of single dose of regorafenib-loaded gastric patch in FaDu cell xenografted tumor bearing athymic nude mice has shown significant (P < 0.05) reduction in the tumor volume over 7 days compared to the control group. Taken together, the multi-layered mucoadhesive gastric patch can be developed as a long-acting oral drug delivery system., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Venkata Vamsi Krishna Venuganti reports financial support, administrative support, equipment, drugs, or supplies, statistical analysis, and travel were provided by Science and Engineering Research Board, India. Sony Priyanka Bandi reports financial support was provided by India Ministry of Science & Technology Department of Science and Technology. Deepanjan Datta reports financial support was provided by Indian Council of Medical Research. Venkata Vamsi Krishna Venuganti has patent pending to BITS Pilani. None, (Copyright © 2022 Elsevier B.V. All rights reserved.)

The aim of the study was to develop and evaluate the efficacy of a functionalized layer-by-layer (LbL) assembled film entrapped with oxaliplatin (OX) and signal transducer and activator of transcription 3 (STAT3) siRNA in the localized treatment of colon cancer. The LbL film was prepared by the sequential layering of chitosan (CS) and alginate to attain desired physical and mechanical properties. The film was functionalized by coating folic acid-conjugated CS on one side. On the other side, polycaprolactone was coated as a backing layer to provide directional drug release. OX was entrapped within the layers of the film, while STAT3 siRNA was complexed with CS to form nanoparticles before entrapment in the LbL film. The CS-siRNA nanoparticles were taken up by the colon carcinoma, Caco-2 cells within 3 h and provided concentration-dependent reduction in STAT3 protein expression. The functionalized LbL film (F-LbL film) selectively adhered to the colon cancer tissue in the mice model, whereas the nonfunctionalized film adhered to the normal colon tissue. The combination of OX and STAT3 siRNA provided significantly greater tumor regression, survival rate, and STAT3 protein suppression after localized delivery through oral administration compared with intravenous administration. Taken together, the F-LbL film can selectively bind to colon tumors for localized delivery of drugs to treat colon cancer.

Localized delivery of chemotherapeutic agents allows extended drug exposure at the target site, thereby reducing systemic toxicity. We report the development of functionalized polymeric patch with unidirectional drug release to treat gastric cancer. The oxaliplatin-loaded patch was prepared by incorporating sodium carboxymethyl cellulose, hydroxypropyl cellulose and polyvinylpyrrolidone. The patch was functionalized by coating with transferrin-poly(lactic-co-glycolic acid) conjugate on one side of the patch for cancer targeting. The other side of the patch was coated with ethylcellulose (EC) to restrict the release of oxaliplatin. The physical and mechanical properties of oxaliplatin-loaded patches were characterized. Mucoadhesion studies using excised rat stomach tissue have shown that the functionalized side of the patch has significantly (p < 0.05) greater mucoadhesion strength compared with EC coated side of the patch. The in vitro and ex vivo (stomach sac and open-membrane model) studies revealed greater permeation of oxaliplatin across the stomach tissue when adhered to the functionalized and non-functionalized side of the patch compared with EC coated side. It was found that the growth inhibition with oxaliplatin solution was not significantly greater compared with corresponding concentrations of oxaliplatin-loaded patch in AGS and Caco-2 cell models. The in vivo studies were performed in mice, where indocyanine green-loaded patch encapsulated in a gelatin capsule was orally administered. The near-infrared (NIR) optical imaging revealed adherence of the patch on the mucosal side of the stomach tissue for up to 6 h. In conclusion, the functionalized polymeric patch loaded with oxaliplatin can be a potential localized delivery system to target gastric cancer., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Mucus is a viscoelastic gel that traps pathogens and other foreign particles to limit their penetration into the underlying epithelium. Dosage forms containing particle-based drug delivery systems are trapped in mucosal layers and will be removed by mucus turnover. Mucoadhesion avoids premature wash-off and prolongs the residence time of drugs on mucus. Moreover, mucus penetration is essential for molecules to access the underlying epithelial tissues. Various strategies have been investigated to achieve mucoadhesion and mucus penetration of drug carriers. Innovations in materials used for the construction of drug-carrier systems allowed the development of different mucoadhesion and mucus penetration delivery systems. Over the last decade, advances in the field of materials chemistry, with a focus on biocompatibility, have led to the expansion of the pool of materials available for drug delivery applications. The choice of materials in mucosal delivery is generally dependent on the intended therapeutic target and nature of the mucosa at the site of absorption. This review presents an up-to-date account of materials including synthesis, physical and chemical modifications of mucoadhesive materials, nanocarriers, viral mimics used for the construction of mucosal drug delivery systems., Competing Interests: Declaration of competing interest The authors report no financial interest that might pose a potential, perceived or real conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)