Silk-based biomaterials for sustained drug delivery

Liposomes have proven to be versatile carriers for the delivery of drugs. These carriers are biocompatible, since they are generally made from lipids commonly found in biologic systems and are biodegradable by the usual metabolic pathways. A sustained drug delivery system is useful when the efficacy of drugs is limited by the inability to maintain therapeutic concentrations. Furthermore, a depot delivery system can offer important advantages in the clinic, such as significantly reducing dose frequency and providing efficacy without toxicity. Because of their small size (<5μ.m), conventional liposomes (unilamellar and multilamellar) are limited in their ability to provide depot delivery of drugs when administered subcutaneously or intramuscularly. The small size of these liposomes results in relatively fast clearance from the injection site and a short duration of delivery, typically 1–4 days. Multivesicular liposomes (MVLs) are distinct from conventional liposomes in composition, structure, and size and are the only class of commercial liposomes that have demonstrated depot delivery of both small molecule and protein/peptide drugs. These MVLs are characterized by the presence of a continuous bilayer membrane, with numerous internal aqueous compartments that are contiguous and separated by bilayer septums. As a result of their larger size (median diameter typically 10–30μ.m), these MVLs are not rapidly cleared by tissue macrophages and can act as a drug depot providing slow release of drugs delivered through different routes of administration. Moreover, the biocompatibility and biodegradability of the MVL lipid matrix allows for the sustained delivery of drugs to sensitive areas. The unique architecture of MVLs provides high drug loading of water-soluble drugs, reasonable stability during storage, and control over the drug-release rate. Furthermore, the lipid composition of MVLs can be altered to deliver therapeutics over periods ranging from a few days to a month, in order to meet specific therapeutic needs. The capability of altering the rate of drug release from MVLs by varying the lipid composition provides a great deal of versatility for controlled delivery of a wide variety of therapeutics. This article reviews depot delivery with conventional liposomes, demonstrates through several examples the sustained depot delivery of small and macromolecular drugs using MVLs, and summarizes some novel delivery systems that combine liposomes with polymeric matrices and have the potential to expand the platform of liposomal depot delivery.

Temperature sensitive copolymer systems were previously studied using modified diffusion cells in vitro for intratympanic injection, and the PLGA-PEG-PLGA copolymer systems were found to provide sustained drug delivery for several days. The objectives of the present study were to assess the safety of PLGA-PEG-PLGA copolymers in intratympanic injection in guinea pigs in vivo and to determine the effects of additives glycerol and poloxamer in PLGA-PEGPLGA upon drug release in the diffusion cells in vitro for sustained inner ear drug delivery. In the experiments, the safety of PLGA-PEG-PLGA copolymers to inner ear was evaluated using auditory brainstem response (ABR). The effects of the additives upon drug release from PLGA-PEG-PLGA hydrogel were investigated in the modified Franz diffusion cells in vitro with cidofovir as the model drug. The phase transition temperatures of the PLGA-PEG-PLGA copolymers in the presence of the additives were also determined. In the ABR safety study, the PLGA-PEG-PLGA copolymer alone did not affect hearing when delivered at 0.05-mL dose but caused hearing loss after 0.1-mL injection. In the drug release study, the incorporation of the bioadhesive additive, poloxamer, in the PLGA-PEG-PLGA formulations was found to decrease the rate of drug release whereas the increase in the concentration of the humectant additive, glycerol, provided the opposite effect. In summary, the PLGA-PEG-PLGA copolymer did not show toxicity to the inner ear at the 0.05-mL dose and could provide sustained release that could be controlled by using the additives for inner ear applications.

One of the challenges of ocular drug delivery systems is sustainable delivery of the intended drug to the posterior segment of the eye. Periocular routes of drug delivery are a promising method to bridge this challenge. The purpose of this study is to investigate the recent advances and potentials of subconjunctival route and its pros and cons in comparison with other ocular drug delivery routes. In this literature review, the comprehensive search of publications was performed in MEDLINE/PubMed indicating investigations on subconjunctival drug delivery systems using relevant keywords. Based on the resultant detailed criteria to choose an appropriate ocular drug delivery route, it is revealed that most of these routes are either highly invasive and/or provide low bioavailability of drug to the target tissue. Nevertheless, subconjunctival drug delivery could be considered as one of the less invasive and easily accessible routes for delivering various drugs to both anterior and posterior segments of the eye. However, most of such researches are at the stage of animal study in their pipelines. Periocular route of drug delivery is one of the most efficient routes for delivering the drugs to both anterior and posterior segments of the eye. Subconjunctival sustained drug delivery is highly effective and less invasive compared to other periocular routes. This makes subconjunctival implants and injections one of the most proper ways of treating various ranges of ocular diseases and disorders, e.g., diabetic retinopathy, dry eye syndrome, glaucoma, etc.

Introduction Glaucoma is a group of progressive optic neuropathies resulting in irreversible blindness. It is associated with an elevation of intraocular pressure (>21 mm Hg) and optic nerve damage. Reduction of the intraocular pressure (IOP) through the administration of ocular hypotensive eye drops is one of the most common therapeutic strategies. Patient adherence to conventional eye drops remains a major obstacle in preventing glaucoma progression. Additional problems emerge from inadequate patient education as well as local and systemic side effects associated with adminstering ocular hypotensive drugs. Areas covered Sustained-release drug delivery systems for glaucoma treatment are classified into extraocular systems including wearable ocular surface devices or multi-use (immediate-release) eye formulations (such as aqueous solutions, gels; ocular inserts, contact lenses, periocular rings, or punctual plugs) and intraocular drug delivery systems (such as intraocular implants, and microspheres for supraciliary drug delivery). Expert opinion Sustained release platforms for the delivery of ocular hypotensive drugs (small molecules and biologics) may improve patient adherence and prevent vision loss. Such innovations will only be widely adopted when efficacy and safety has been established through large-scale trials. Sustained release drug delivery can improve glaucoma treatment adherence and reverse/prevent vision deterioration. It is expected that these approaches will improve clinical management and prognosis of glaucoma.

The present study focused on the formulation and evaluation of Ketotifen Fumarate transdermal patches to overcome limitations of oral therapy, such as sedation and gastrointestinal side effects, and to enhance patient compliance through sustained drug delivery. Preformulation studies confirmed the drug’s characteristic organoleptic properties, including its white to off-white crystalline, odorless, and bitter-tasting nature. Eight transdermal patch formulations (KFT-P1 to KFT-P8) were prepared and assessed for critical parameters including pH (5.1–6.3), thickness (0.48–0.57 mm), weight variation (112.35–126.35 mg) and surface pH (5.4–5.8), all within skin-compatible ranges. Mechanical evaluations revealed strong folding endurance (77–98.24%), tensile strength (3.27–4.72 N/mm²), and moisture content (3.24–4.12%), indicating durability, flexibility, and adequate stability. Spreadability (4.45–6.95 g·cm/sec) ensured ease of application, while drug content was uniform (92.55–96.27%), confirming efficient drug loading. Physical appearance assessments highlighted smooth and flexible patches as most suitable for therapeutic use. Overall, the results demonstrate that Ketotifen Fumarate transdermal patches possess desirable physicochemical and mechanical attributes, making them promising candidates for sustained transdermal drug delivery.

The present study aimed to develop and evaluate a diclofenac sodium-loaded nanostructured lipid carrier (NLC) gel for enhanced topical management of arthritis. Diclofenac sodium-loaded NLCs were prepared using the solvent injection technique and incorporated into Carbopol 940 gel to improve topical applicability and sustained drug delivery. The optimized NLC gel was characterized for physicochemical properties, in vitro drug release, ex vivo skin permeation and retention, and In Vivo anti-arthritic efficacy. The optimized formulation exhibited acceptable pH, viscosity, spreadability, and uniform drug content, along with sustained drug release over 12 h. Ex vivo studies using porcine skin demonstrated significantly enhanced drug permeation and skin retention for the NLC gel compared to marketed diclofenac gel and blank gel. In Vivo evaluation in Complete Freund’s Adjuvant-induced arthritic rats revealed a pronounced reduction in paw edema, arthritis score, and improvement in body weight in animals treated with diclofenac sodium NLC gel. Histopathological analysis further confirmed reduced synovial hyperplasia, inflammatory cell infiltration, cartilage erosion, and bone destruction, indicating effective suppression of arthritic pathology. Overall, the findings suggest that diclofenac sodium-loaded NLC gel offers superior topical anti-arthritic efficacy with sustained local drug delivery and reduced systemic burden, making it a promising alternative for localized arthritis therapy.

Biomimetic self-assembly of calcium phosphate templated by PNIPAAm nanogels for sustained smart drug delivery

To investigate PTSgels (Pentablock copolymers) as an injectable formulation technology for sustained ocular drug delivery. Drug release profile, tolerability, and polymer degradation for one of the thermosensitive, biodegradable, and biocompatible compositions were investigated through intracameral (IC) injection in rabbits. New Zealand White rabbit eyes were injected IC (50 μL) with 100 μg near-infrared-immunoglobulin G (NIR-IgG) in balanced salt solution (BSS) or 20% PTSgel; or with PTSgel or BSS alone. Ocular irritation scoring, intraocular pressure (IOP), and corneal thickness (CT) measurement, as well as color and infrared photography, were performed for up to 28 days postinjection. Upon euthanasia at 7, 14, or 28 days, eyes underwent ex vivo imaging (Xenogen IVIS) followed by tissue fixation and histopathology. IC injection of PTSgel (liquid at room temperature) was performed without difficulty using a 31G needle. The polymer quickly gelled in the IC space resulting in an inferior anterior chamber deposit. The tested PTSgel was well tolerated, with no significant changes in IOP or CT. Eyes injected with NIR-IgG in PTSgel had visible NIR-IgG through 9 days postinjection, and ex vivo imaging detected a strong NIR-IgG signal in the anterior chamber through day 28. The gel deposit steadily decreased in size over time and was nearly eliminated by 28 days. The PTSgel released IgG for 28 days and was well tolerated. The polymer degraded in parallel with drug release. These results demonstrate the potential of intracameral PTSgel formulations for sustained delivery of biologic therapies to the ocular anterior segment.

Fundamental investigation of sustained and controlled therapeutics release from 3D printed medical devices

A green chemistry approach towards synthesizing hydrogel for sustained ocular delivery of brinzolamide: In vitro and ex vivo evaluation

Mechanically tuned nanocomposite coating on titanium metal with integrated properties of biofilm inhibition, cell proliferation, and sustained drug delivery

Galactomannans are natural biopolymers possessing efficient biocompatibility, biodegradability, and sustainability, leading to diverse industrial applications. The present work aimed to synthesize a novel hydrogel for drug delivery systems using Cassia galactomannan (galactose to mannose ratio, 1/5) and sodium trimetaphosphate. The hydrogels are used as sustained drug delivery agents for colon cancer treatments and other colonic diseases. The zero order, first order, Higuchi's and Korsmeyer-Peppas models were used to study the release kinetics of the drug, (±)-2-(p-isobutylphenyl)propionic acid. The gels possess controlled water absorption, solubility and increased stability, a requirement for controlled drug delivery applications. The studies reveal that the lower and higher cross-ligate hydrogels were effective in sustained release of 27 and 10 % drug respectively in 24 h. Korsmeyer-Peppas kinetic model showed that the drug release mechanism is controlled diffusion from polymeric gel matrix. Nuclear magnetic spectroscopy 31P, 1H, 13C, DEPT, COSY, HSQC and infrared spectroscopy (FT-IR) proved the formation of new covalent bonds between phosphate and hydroxyls groups that reinforced hydrogel into effective network density and controlled swelling power.

RSM optimized chitosan based composite hydrogel for sustained drug delivery applications

Fluocinolone acetonide sustained drug delivery device to treat severe uveitis

The main objective of sustained release drug delivery system is to provide a steady state blood plasma level concentration which is non-toxic and therapeutically active for a longer period of time. Owing its increased patient compliance and prolonged release of action in delivering drugs several benefits can be contemplated in delivering of sustained release dosage form[1]. Among various route of drug delivery Sustained release drug delivery is most widely preferred as it’s less frequency of dosing and controls the release of drugs. Natural polymers are biodegradable and nontoxic in nature with reduced side effects. It is also eco-friendly and safe to be administered as compared to synthetic polymers. The current work was based on preparation of sustained release tablets of Propranolol Hydrochloride using natural polymers like Gum Acacia, Hibiscus Rosasinesis and Microcrystalline cellulose. Presently much attention is being paid for formulation of sustained release tablets that contains matrix system. Direct compression method was used for formulation of sustained release tablets of Propranolol Hydrochloride. The prepared tablets were evaluated for different pre-formulation studies and in vitro dissolution studies were performed using USP-III dissolution apparatus. Dissolution studies of different formulations were evaluated for 24 hours at 370C.