Sustained Drug Delivery Research Articles

Sulfonamide Prodrugs with a Two-Stage Release Mechanism for the Efficient Delivery of the TLR4 Antagonist TAK-242.

We previously demonstrated that the potent TLR4 inhibitor TAK-242 could be covalently conjugated to pancreatic islets using a linker that afforded an effective sustained delivery of the active drug after transplant. This drug-eluting tissue achieved local inhibition of TLR4-linked inflammation and proved beneficial to the islet graft survival. Here, we describe a new family of prodrugs with a modular design featuring a self-immolative para-aminobenzyl spacer bonded directly to the TAK-242 sulfonamide nitrogen, a tether for bioconjugation, and a β-eliminative arylsulfone "trigger". The inclusion of the para-aminobenzyl spacer affords a more stable prodrug which exhibits complex drug-release kinetics due to a two-stage release mechanism. This manuscript reports the preparation and characterization of several TAK-242 prodrugs fitted with different triggers and linkers and demonstrates that these second-generation prodrugs effectively release TAK-242 while avoiding nonproductive sulfonamide hydrolysis.

Locoregional Lymphatic Delivery Systems Using Nanoparticles and Hydrogels for Anticancer Immunotherapy.

The lymphatic system has gained significant interest as a target tissue to control cancer progress, which highlights its central role in adaptive immune response. Numerous mechanistic studies have revealed the benefits of nano-sized materials in the transport of various cargos to lymph nodes, overcoming barriers associated with lymphatic physiology. The potential of sustained drug delivery systems in improving the therapeutic index of various immune modulating agents is also being actively discussed. Herein, we aim to discuss design rationales and principles of locoregional lymphatic drug delivery systems for invigorating adaptive immune response for efficient antitumor immunotherapy and provide examples of various advanced nanoparticle- and hydrogel-based formulations.

Recent Advancement on TDDS (Transdermal Drug Delivery System)

The creation of a transdermal drug delivery system (TDDS) has been one of the most sophisticated and innovative approaches to drug delivery. The transdermal drug delivery system has attracted considerable attention because of its many potential advantages, including better patient compliance, avoidance of gastrointestinal disturbances, hepatic first-pass metabolism, and sustained delivery of drugs to provide steady plasma profiles, particularly for drugs with short half-lives, reduction in systemic side effects and enhanced therapeutic efficacy. This review article covers a brief outline of the transdermal drug delivery system; Highlight the restrictions, drawbacks, shortcomings, and Versatile benefits of delivery systems.

Both non-coated and polyelectrolytically-coated intraocular collagen-alginate composite gels enhanced photoreceptor survival in retinal degeneration

Treatments of vision-threatening retinal diseases are often hampered by drug delivery difficulties. Polyelectrolytically-coated alginate encapsulated-cell therapy (ECT) systems have shown therapeutic efficacy through prolonged in vivo drug delivery but still face various biocompatibility, viability, drug delivery and mechanical stability issues in clinical trials. Here, novel, injectable alginate-poly-l-lysine (AP)-coated composite alginate-collagen (CAC) ECT gels were developed for sustained ocular drug delivery, and their long-term performance was compared with non-coated CAC ECT gels. All optimised AP-coated gels (AP1- and AP5.5-CAC ECT: 2 mg/ml collagen, 1.5% high molecular weight alginate, 50,000 cells/gel, with 0.01% or 0.05% poly-l-lysine coating for 5 min, followed by 0.15% alginate coating) and non-coated gels showed effective cell proliferation control, cell viability support and continuous delivery of bioactive glial cell-derived neurotrophic factor (GDNF) with no significant gel degradation in vitro and in rat vitreous. Most importantly, intravitreally injected gels demonstrated therapeutic efficacy in Royal College of Surgeons rats with retinal degeneration, resulting in reduced photoreceptor apoptosis and retinal function loss. At 6 months post-implantation, no host-tissue attachment or ingrowth was detected on the retrieved gels. Non-coated gels were mechanically more stable than AP5.5-coated ones under the current cell loading. This study demonstrated that both coated and non-coated ECT gels can serve as well-controlled, sustained drug delivery platforms for treating posterior eye diseases without immunosuppression.

Low cost production of bacterial cellulose through statistical optimization and developing its composites for multipurpose applications

The current investigation reports the enhanced bacterial cellulose (BC) productivity from previously isolated bacteria, Enterobacter hormaechei subsp. steigerwaltii strain ZKE7 using different raw sources. Optimization by Plackett–Burman and central composite designs revealed improved BC production of 31.7 g/L BC (In-situ) with 7.54-fold enhancement. Different BC composites were synthesized using optimized In-situ BC that showed excellent water retention capability, moisture content, water release rate, porosity, thickness and protein adsorption. In vitro drug (methylene blue dye and ceftriaxone) release profile of the composites (BC-Cu and BC-CMC) suggested a sustained drug delivery and indicated a non-Fickian diffusion behavior based on Peppas model. The quick catalytic activity of BC-Cu in fast reduction of 4-nitrophenol was demonstrated spectrophotometrically with decline in the characteristic absorbance peak of 4-nitrophenol. In-situ BC and composites exhibited antimicrobial properties with differential activity against different pathogens. Significant antibacterial and inhibitory effect was evidenced against Bacillus cereus. Only In-situ BC showed a pronounced antifungal activity against Candida albicans. In-situ BC and composites were characterized by various analytical techniques including FTIR, SEM-EDS, TGA and DSC. The current study reveals enhanced BC yield with the reduction of 4-nitrophenol by BC-Cu composite and antimicrobial property suggests its employability in drug delivery systems and environmental applications.

Chitosan and carboxymethyl cellulose-based 3D multifunctional bioactive hydrogels loaded with nano-curcumin for synergistic diabetic wound repair

Biopolymer-based thermoresponsive injectable hydrogels with multifunctional tunable characteristics containing anti-oxidative, biocompatibility, anti-infection, tissue regeneration, and/or anti-bacterial are of abundant interest to proficiently stimulate diabetic wound regeneration and are considered as a potential candidate for diversified biomedical application but the development of such hydrogels remains a challenge. In this study, the Chitosan-CMC-g-PF127 injectable hydrogels are developed using solvent casting. The Curcumin (Cur) Chitosan-CMC-g-PF127 injectable hydrogels possess viscoelastic behavior, good swelling properties, and a controlled release profile. The degree of substitution (% DS), thermal stability, morphological behavior, and crystalline characteristics of the developed injectable hydrogels is confirmed using nuclear magnetic resonance (1H NMR), thermogravimetric analysis, scanning electron microscopy (SEM), and x-ray diffraction analysis (XRD), respectively. The controlled release of cur-micelles from the hydrogel is evaluated by drug release studies and pharmacokinetic profile (PK) using high-performance liquid chromatography (HPLC). Furthermore, compared to cur micelles the Cur-laden injectable hydrogel shows a significant increase in half-life (t1/2) up to 5.92 ± 0.7 h, mean residence time (MRT) was 15.75 ± 0.76 h, and area under the first moment curve (AUMC) is 3195.62 ± 547.99 μg/mL*(h)2 which reveals the controlled release behavior. Cytocompatibility analysis of Chitosan-CMC-g-PF127 hydrogels using 3T3-L1 fibroblasts cells and in vivo toxicity by subcutaneous injection followed by histological examination confirmed good biocompatibility of Cur-micelles loaded hydrogels. The histological results revealed the promising tissue regenerative ability and shows enhancement of fibroblasts, keratinocytes, and collagen deposition, which stimulates the epidermal junction. Interestingly, the Chitosan-CMC-g-PF127 injectable hydrogels ladened Cur exhibited a swift wound repair potential by up-surging the cell migration and proliferation at the site of injury and providing a sustained drug delivery platform for hydrophobic moieties.

Synthesis, characterization, and acute toxicity of pH-responsive Salvia spinosa mucilage-co-acrylic acid hydrogel: A smart excipient for drug release applications

Owing to the increasing demand for pH-responsive excipients based on natural polysaccharides, a copolymeric biocomposite material was developed for sustained release drug delivery system (DDS). A novel pH-responsive, non-toxic, and superabsorbent graft copolymeric hydrogel (SSH-co-AA) based on mucilage from Salvia spinosa seeds (SSH) and acrylic acid (AA; monomer) was fabricated through free radical copolymerization using N,N′-methylene-bis-acrylamide (MBA; cross-linker) and potassium persulfate (KPS; initiator). The Fourier transform infrared and CP/MAS 13C‐NMR solid-state NMR spectroscopic analyses confirmed the successful grafting of AA onto SSH. The Powder X-ray diffraction analysis indicated the complete entrapment of crystalline drug in the amorphous polymeric network. Newly fabricated hydrogel is thermally more stable than SSH as revealed through thermogravimetric analysis (TGA). The scanning electron microscopic images indicated the porous nature of SSH-co-AA. An increase in the gel fraction is observed by increasing the concentration of SSH, AA, and MBA. The porosity of SSH-co-AA is directly proportional to the concentration of SSH and AA and inversely proportional to the concentration of MBA. The swelling of SSH-co-AA followed second-order kinetics and the sustained release of venlafaxine HCl followed the Korsmeyer-Peppas model and non-fickian diffusion mechanism. Acute oral toxicity studies of SSH-co-AA reported non-toxic and non-irritant attributes.

Formulation and Evaluation Tolbutamide Liposomes for a Sustained Drug Delivery System

Novel Drug Delivery system (NDDS) refers to the approaches, formulations, technologies, and systems for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effects. Applications of liposomes in medicine and pharmacology can be divided into diagnostic and therapeutic applications of liposomes containing various markers or drugs. The aim of the study was to formulate and evaluate Tolbutamide liposomes for a sustained drug delivery system. The tolbutamide was prepared as a liposomal drug delivery system by using two different techniques such as physical dispersion method and ether injection method. The morphological characters of prepared liposomes were determined with the help of optical microscope. The results of the particle size showed, when the concentration of soya lecithin was increased the size of the particle was reduced. The in vitro release showed that as the concentration of soya lecithin was increased the release rate of drug was retarded. Among the two methods ether injection method showed prolonged action when compared to physical dispersion method. The stability studies for all the formulations were performed by keeping the formulations at two different temperatures 4ºC±2ºC and 25ºC±2ºC for a period of 30 days. There was no change in morphological characters at 4ºC±2ºC, but there was a slight reduced in particles size at 25ºC±2ºC. The percentage drug entrapment was reduced in all the formulations at both the conditions.

Development of injectable thermoresponsive Cs‐g‐PNIPAAm hydrogel for intrascleral drug delivery of sunitinib malate for the posterior segment ocular disease, age‐related macular degeneration

AbstractBackground: Age‐related macular degeneration (AMD) is a potentially blinding posterior segment disease; inflammatory responses and subretinal drusen formation lead to leaky blood vessels. The current treatment method involves intravitreal injections of anti‐VEGF agents, which is highly invasive and requires frequent injections administered by trained personnel. Periocular injections such as trans−/intra‐scleral injections would provide a minimally‐invasive treatment option. The sclera is the outermost protective layer occupying 5/6th of the ocular globe. Owing to its avascular nature and self‐healing ability, sclera could be the potential space for the delivery of depot forming long‐acting formulations. This project focuses on the development of chitosan grafted poly(n‐isopropylacrylamide) (Cs‐g‐PNIPAAm) gel for the sustained intrascleral delivery of small molecular weight, multiple tyrosine kinase inhibitor Sunitinib malate.Methods: Cs‐g‐PNIPAAm hydrogel was prepared using free radical polymerization with varying concentrations of chitosan (varying with 10%, 30%, 50% weight percentages) with respect to PNIPAAm. The hydrogels were characterized for rheology, LCST measurements, swelling studies, degradation, syringeability, drug release and permeation using Franz diffusion studies. Biocompatibility study of hydrogel was performed with ARPE‐19 cells, ocular irritation using HET‐CAM test, Further, choroidal angiogenesis was tested on CAM assay and rat choroidal exoplants.Results: Chitosan grafting was found to have effect on rheological properties of hydrogel and hence on syringeability of formulations. However, chitosan grafting did not significantly affect the LCST of hydrogels, all the formulations exhibited LCST of 32 ± 0.5°C. 20 ul of 30% Cs‐g‐PNIPAAm hydrogel was able to release approximately 10 ug/day sunitinib concentration in‐vitro for 28 days. It was observed that the drug release from the hydrogel was controlled by both the diffusion and erosion mechanism. Further, the ex‐vivo permeation studies on porcine sclera showed that up to 40% sustained release of sunitinib was obtained from hydrogel compared to sunitinib solution (2 mg/ml). The optimized formulation (F8) was found to be biocompatible on ARPE‐19 cells and no ocular irritation was observed on HET‐CAM (Hen's egg test‐ Choriallantoic membrane) assay. Further, the anti‐angiogenic efficacy was conformed using CAM assay and rat‐choroidal angiogenesis assay. Wherein F8 hydrogel was found to prevent formation of new blood capillaries compared to control medium.Conclusions: The F8 hydrogel was found to be injectable using ultra‐thin walled 27G needles. OCT micrographs shows that the F8 hydrogel is able to form depot on‐intrascleral injections. Further, dual control over the drug release i.e. temperature controlled gelation and ionic conjugation of sunitinib with amine group of chitosan gives better control over drug release. Hence, Cs‐g‐PNIPAAm hydrogel would be a minimally invasive sustained release drug delivery alternative to intravitreal injections for the management of AMD.

Development and optimization of RofA-PAMAM dendrimer complex materials for sustained drug delivery

The current indagation is observed on anatomization of drug release dynamics aiming at preceding the anti-inflammation activity of roflumilast analogue (RofA), post assemblage with dendrimer. The study pondered the development and optimization of RofA-Dendrimer complexes for sustained delivery. Many physiological and physicochemical factors, like encapsulation potency, drug loading, drug release, dissolvability, stability, and anti-inflammation activity were determined. The study results in the observation of encapsulation potency of 72.64 ± 0.189%, loading capability of 63.41 ± 0.166%, and in vitro release of RofA-4.0 G PAMAM complex was found to increase making it an appropriate candidate for sustained drug release progressively . It has been found by constructing drug release kinetics, that the release followed was a non- fickian diffusion ( n<0.89). The phase solubility diagram indicated an increment of solubility of RofA with varied dendrimer generation as well as pH. The study was initiated to prepare a suited candidate fit to scale back site-specific inflammation. Further concluding the contemplation for its sustained delivery, enhanced solubility, and potentially augmented anti-inflammation activity. • The aims of this study were to assess the potentially augmented effect of roflumilast analogue post assemblage with different generations of polyamidoamine dendrimer. • In this study, RofA-Dendrimer complexes, with RofA as the model drug, the encapsulation potency, loading capacity, in vitro drug release behavior, and stability were studied. • The effect of the concentration of varied generations of PAMAM dendrimer on the solubility of RofA has been discussed in detail. • We also examined the anti-inflammatory activity and sought to determine the inhibitory effect on protein denaturation. • The results were affirmed by the determination of n value i.e. hill coefficient with respect to the substrate concentration and rate of inhibition. • The impact of adjuvant antibiotic therapy was also explored by the means of a cytotoxicity assay.

A tetracycline hydrochloride-loaded SiO2/polycaprolactone composite from bamboo stem for controlled drug release study

A controlled drug delivery system is preferable to traditional drug administration because it can supply the drug continuously and ensure on-demand bioavailability. The production of silica/polymer composite delivery material is expensive due to the use of alkoxysilane silica precursors. As bamboo is an abundant plant in Africa, we investigated the use of bamboo stems as an alternative silica starting material. The ash from the bamboo stem was mixed with polycaprolactone (PCL) solution to produce a (SiO2/PCL) composite, which was then loaded with the drug, tetracycline hydrochloride (TCH), to test in vitro degradability and controlled-release in phosphate-buffered saline (PBS). Scanning electron microscopy, X-ray diffractometry and Fourier transform infrared spectroscopy were used to examine the structure, phase composition, and chemical bond properties of the material. The TCH release profile was determined using an ultraviolet (UV) spectrophotometer. The SiO2/PCL composite showed a high capacity for drug loading. The composite released TCH in a consistent and sustained way, and showed regulated degradability in PBS. As a result, the use of bamboo stem-derived silica in the formulation of SiO2/PCL for continuous TCH delivery shows considerable cost-benefit potential for a safe, regulated drug delivery strategy. Significance: This study shows the benefit of using bamboo stem as an alternative silica source to alkoxysilanes. SiO2/PCL composites can be employed for the sustained delivery of drugs while providing congruent degradation. This study can serve as a benchmark for further utilisation of bamboo stem as a low-cost silica precursor.

Preparation and Characterization of Salsalate-Loaded Chitosan Nanoparticles: In Vitro Release and Antibacterial and Antibiofilm Activity.

The controlled-release characteristic of drug delivery systems is utilized to increase the residence time of therapeutic agents in the human body. This study aimed to formulate and characterize salsalate (SSL)-loaded chitosan nanoparticles (CSNPs) prepared using the ionic gelation method and to assess their in vitro release and antibacterial and antibiofilm activities. The optimized CSNPs and CSNP-SSL formulation were characterized for particle size (156.4 ± 12.7 nm and 132.8 ± 17.4 nm), polydispersity index (0.489 ± 0.011 and 0.236 ± 132 0.021), zeta potential (68 ± 16 mV and 37 ± 11 mV), and entrapment efficiency (68.9 ± 2.14%). Physicochemical features of these nanoparticles were characterized using UV-visible and Fourier transform infrared spectroscopy and X-ray diffraction pattern. Scanning electron microscopy studies indicated that CSNPs and CSNP-SSL were spherical in shape with a smooth surface and their particle size ranged between 200 and 500 nm. In vitro release profiles of the optimized formulations showed an initial burst followed by slow and sustained drug release after 18 h (64.2 ± 3.2%) and 48 h (84.6 ± 4.23%), respectively. Additionally, the CSNPs and CSNP-SSL nanoparticles showed a sustained antibacterial action against Staphylococcus aureus (15.7 ± 0.1 and 19.1 ± 1.2 mm) and Escherichia coli (17.5 ± 0.8 and 21.6 ± 1.7 243 mm). Interestingly, CSNP-SSL showed better capability (89.4 ± 1.2% and 95.8 ± 0.7%) than did CSNPs in inhibiting antibiofilm production by Enterobacter tabaci (E2) and Klebsiella quasipneumoniae (SC3). Therefore, CSNPs are a promising dosage form for sustained drug delivery and enhanced antibacterial and antibiofilm activity of SSL; these results could be translated into increased patient compliance.

4D prints of flexible dosage forms using thermoplastic polyurethane with hybrid shape memory effect

Thermoplastic polyurethanes are versatile materials due to their flexible and elastic properties. In research, medicine, and pharmacy, they are used in dosage forms, implants or as components of medical devices. To gain a deeper understanding of the influences on unfolding or expanding dosage forms, in this publication, 3D printing was used to produce differently shaped and foldable objects from various technical thermoplastic polyurethane filaments. The shape memory behaviour of the dosage forms was exploited to fold and package them in water-soluble hard gelatin capsules. The unfolding time and dimensional recovery of the 3D printed dosage forms were investigated as a function of material properties and shape. As an example, for the use of flexible dosage forms, 3D models have been designed so that their unfolded size is suitable for possible gastric retention. Depending on the shape and material, different unfolding behaviours could be shown. Over a storage period of 60 days, a time related stress on the 4D printed objects was evaluated, which possibly affects the unfolding process. The results of this work aim to be used to evaluate the behaviour of 3D printed unfolding and expanding dosage forms and how they may be suitable for the development of innovative sustained drug delivery concepts or medicinal devices. The basic principle of a hybrid shape memory effect used here could possibly be applied to other drug delivery strategies besides gastric retention.

Hispolon Cyclodextrin Complexes and Their Inclusion in Liposomes for Enhanced Delivery in Melanoma Cell Lines.

Hispolon, a phenolic pigment isolated from the mushroom species Phellinus linteus, has been investigated for anti-inflammatory, antioxidant, and anticancer properties; however, low solubility and poor bioavailability have limited its potential clinical translation. In this study, the inclusion complex of hispolon with Sulfobutylether-β-cyclodextrin (SBEβCD) was characterized, and the Hispolon-SBEβCD Complex (HSC) was included within the sterically stabilized liposomes (SL) to further investigate its anticancer activity against melanoma cell lines. The HSC-trapped-Liposome (HSC-SL) formulation was investigated for its sustained drug delivery and enhanced cytotoxicity. The inclusion complex in the solid=state was confirmed by a Job's plot analysis, molecular modeling, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Proton nuclear magnetic resonance (NMR) spectroscopy, and scanning electron microscopy (SEM). The HSC-SL showed no appreciable deviation in size (&lt;150 nm) and polydispersity index (&lt;0.2) and improved drug encapsulation efficiency (&gt;90%) as compared to control hispolon liposomes. Individually incorporated hispolon and SBEβCD in the liposomes (H-CD-SL) was not significant in loading the drug in the liposomes, compared to HSC-SL, as a substantial amount of free drug was separated during dialysis. The HSC-SL formulation showed a sustained release compared to hispolon liposomes (H-SLs) and Hispolon-SBEβCD liposomes (H-CD-SLs). The anticancer activity on melanoma cell lines (B16BL6) of HSC and HSC-SL was higher than in H-CD-SL and hispolon solution. These findings suggest that HSC inclusion in the HSC-SL liposomes stands out as a potential formulation approach for enhancing drug loading, encapsulation, and chemotherapeutic efficiency of hispolon and similar water insoluble drug molecules.

Preparation and Evaluation of Sustained Release Tablet of Rifaximin by using Cross linked Sodium Alginate

Rifaximin treats traveler's diarrhea and irritable bowel syndrome by stopping the growth of the bacteria that cause diarrhea. Rifaximin treats hepatic encephalopathy by stopping the growth of bacteria that produce toxins and that may worsen liver disease. The short half life and high frequency of administration of drug makes it a suitable candidate for designing sustained drug delivery system. The aim of the present investigation was to develop a sustained release matrix tablet of Rifaximin using sodium alginate and cross linked sodium alginate and to evaluate the drug release kinetics. In order to achieve the required sustained release profile, the tablets were prepared by a wet granulation method. The formulated tablets were characterized for pre-compression and post-compression parameters and they were in the acceptable limits. The drug release data obtained after an in vitro dissolution study was fitted to various release kinetic models in order to evaluate the release mechanism and kinetics. The criterion for selecting the best fit model was linearity (coefficient of correlation). Drug release mechanism was found to follow a complex mixture of diffusion, swelling and erosion. The dosage form holds the potential to control the release rate of drug and extend the duration of action of a drug.

Floating Drug Delivery System: A Novel apporach for Delivery of Drug on Targated Organ

The goal of this review on floating drug delivery systems (FDDS) was to compile latest data with a particular focus on the main mechanism of flotation for stomach retention. Drug delivery systems that float instantly when they come into contact with gastric fluids are promising approaches for increasing the bioavailability of drugs within absorption window in the stomach or upper small intestine. They are unstable in the intestinal or colonic environment and have low solubility at high pH values. The Current pharmaceutical scenario focuses on the development of sustained drug delivery systems to achieve required therapeutic concentration with less amount of dose. Oral delivery of the drug is the preferable drug delivery system. Because of the ease of administration, patient compliance and formulation flexibility. The ability to delay and control the emptying period of a dosage form in the stomach is an extremely variable process. For dosage forms that stay in the stomach for longer periods of time than standard dosage forms so the gastric transit time is a valuable asset for this system. The goal of this review article is to provide detailed information on the pharmaceutical basis of their design, classification, advantages, in vitro and in vivo evaluation parameters, and applications of floating systems. These systems can help with a variety of issues that arise during the development of a pharmaceutical dosage form, as well as the potential of FDDS in the future. This review article makes an attempt to introduce readers to current developments in floating drug delivery systems.

Formulation of an implantable device from mini tablets-in-PCL cylinders for sustained delivery of a hydrophobic drug

Implantable drug delivery systems are presented as a potential alternative to current treatments of chronic conditions. The aim of this work was to formulate a subcutaneous implantable device made with prefabricated poly(caprolactone) (PCL) cylinders, loaded with olanzapine (OLZ) as a model drug and cyclodextrin in a mass ratio of 1:1. The final formulation was characterized using optical microscopy,&amp;nbsp;infrared spectroscopy, thermal analysis, and X-ray diffraction. The proposed device was successfully fabricated and demonstrated ability to control drug release for 60 days. With continued development, these novel implants could be an alternative to currently available treatments for schizophrenia.

Programmable self-regulated molecular buffers for precise sustained drug delivery

Unlike artificial nanosystems, biological systems are ideally engineered to respond to their environment. As such, natural molecular buffers ensure precise and quantitative delivery of specific molecules through self-regulated mechanisms based on Le Chatelier’s principle. Here, we apply this principle to design self-regulated nucleic acid molecular buffers for the chemotherapeutic drug doxorubicin and the antimalarial agent quinine. We show that these aptamer-based buffers can be programmed to maintain any specific desired concentration of free drug both in vitro and in vivo and enable the optimization of the chemical stability, partition coefficient, pharmacokinetics and biodistribution of the drug. These programmable buffers can be built from any polymer and should improve patient therapeutic outcome by enhancing drug activity and minimizing adverse effects and dosage frequency.

CUBOSOMES: A BOON FOR COSMECEUTICALS AND TOPICAL DRUG DELIVERY

Cubosomes are the nanoparticles of bicontinuous, lyotropic cubic phases, comprised of curved lipid bilayers organized into a three-dimensional honeycomb (cavernous) like structures separating two internal aqueous channels and large interfacial area. Cubic phases are optically isotropic, very viscous, and solid-like (crystalline) with cubic crystallographic symmetry. They can encapsulate hydrophilic, hydrophobic and amphiphilic drug substances, which are able to target and control the release of the bioactive agent. The cosmetic industry has made progress in the development of products to overcome skin as a barrier and deliver the actives through the skin effectively. Drug incorporated cubosomes shows some unique advantageous like, protection from chemical and physiological degradation, in vivo drug release in a controlled manner and improving the bioavailability of drug while reducing the side effect. Cubosomes are pharmacologically inactive, non-irritant, non-toxic, effective, and cosmetically acceptable. Topical drug delivery can deliver drugs selectively to the specific site; this avoids fluctuations of drug levels and improves patient compliance and suitable local and systemic therapeutic effects. Cubosomal topical drug formulation shows outstanding potential advantages for their controlled and sustained drug delivery. This review article mainly focuses on cosmetic and topical applications of cubosomes.

Injectable Polymer‐Nanoparticle Hydrogel for the Sustained Intravitreal Delivery of Bimatoprost

AbstractVision impairment resulting from chronic eye diseases, such as macular degeneration and glaucoma, severely impacts patients’ quality of life and poses an immense global financial burden. Current standard of care for such diseases includes daily eye drops or frequent intravitreal (ITV) injections, which are burdensome treatment modalities resulting in low patient compliance. There remains a growing need for easily administered long‐acting delivery technologies for prolonging exposure of ocular therapeutics with each administration. Here, this work deploys a supramolecular polymer‐nanoparticle (PNP) hydrogel for ITV delivery of the glaucoma drug bimatoprost. PNP hydrogels are shear‐thinning and self‐healing, key properties for injectability, and enable slow release of molecular cargo in vitreous humor (VH) mimics. An in vivo study in New Zealand white rabbits demonstrated intravitreally injected PNP hydrogels form depots that degrade slowly over time, maintaining detectable levels of bimatoprost in the VH up to 8 weeks following injection. Ophthalmic examinations and histopathology identified a mild foreign body response (FBR) to the hydrogel, characterized by rare clusters of foamy macrophages and giant cells associated with minimal, patchy fibroplasia. This work shows that PNP hydrogels exhibit numerous desirable traits for sustained drug delivery and further work will be necessary to optimize tolerability in the eye.