Nano Co-Crystal Embedded Stimuli-Responsive Hydrogels: A Potential Approach to Treat HIV/AIDS

Abstract

Currently, the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) can only be treated successfully, using combination antiretroviral (ARV) therapy. Lamivudine (3TC) and zidovudine (AZT), two compounds used for the treatment of HIV and prevention of disease progression to AIDS are used in such combinations. Successful therapy with 3TC and AZT requires frequent dosing that may lead to reduced adherence, resistance and consequently treatment failure. Improved toxicity profiles of 3TC and AZT were observed when combined as a nano co-crystal (NCC). The use of stimuli-responsive delivery systems provides an opportunity to overcome the challenge of frequent dosing, by controlling and/or sustaining delivery of drugs. Preliminary studies undertaken to identify a suitable composition for a stimulus-responsive in situ forming hydrogel carrier for 3TC-AZT NCC were conducted, and the gelation and erosion time were determined. A 25% w/w Pluronic® F-127 thermoresponsive hydrogel was identified as a suitable carrier as it exhibited a gelation time of 5 min and an erosion time of 7 days. NCC-loaded hydrogels were evaluated using in vitro dissolution and cytotoxicity assays. In vitro dissolution undertaken using membrane-less diffusion over 168 h revealed that 3TC and AZT release from NCC-loaded hydrogels was complete and followed zero-order kinetic processes, whereas those loaded with the micro co-crystal and physical mixture were incomplete and best described using the Korsmeyer–Peppas kinetic model. The release of AZT and 3TC from the physical mixture and MCC-loaded gel exhibited a value for n of 0.595 for AZT release from the physical mixture and 0.540 for the MCC technology, whereas the release exponent for 3TC was 0.513 for the physical mixture and 0.557 for the MCC technology indicating that diffusion and erosion controlled 3TC and AZT release. In vitro cytotoxicity assay data revealed that the addition of NCC to the thermoresponsive hydrogel resulted in an improved cell viability of 88.0% ± 5.0% when compared to the cell viability of the NCC of 76.9% ± 5.0%. The results suggest that the use of a thermoresponsive nanosuspension may have the potential to be delivered as an intramuscular injection that can subsequently increase bioavailability and permit dose reduction and/or permit use of a longer dosing frequency.

A SWOT analysis of nano co-crystals in drug delivery: present outlook and future perspectives

“…This has been demonstrated in the manufacture of an NCC formulation to potentially delivery both lamivudine and zidovudine for the management of HIV/AIDS. 48,55,81,82…”

“…This has been demonstrated in the manufacture of an NCC formulation to potentially delivery both lamivudine and zidovudine for the management of HIV/AIDS. 48,55,81,82 Similarly, Pi et al, demonstrated the possibility of combining the botanical therapeutic baicalein and nicotinamide to improve the solubility of the baicalein. 41 The authors were able to manufacture a formulation capable of increasing the bioavailability of the baicalein while also being able to deliver nicotinamide.…”

“…While additive manufacturing has not been demonstrated much specifically for NCC, it has been attempted to further develop NCC of antiretroviral drugs into a stimuli responsive gel allowing for potential sustained/controlled release of the payload. 82 It was reported that the stimuli responsive carrier was able to sustain the release of the payload for up to 168 hours in vitro . The authors do, however, maintain that there is a need for more studies pertaining to the actual implications of these data when applied to in vivo models.…”

Cellulosic Polymers for Enhancing Drug Bioavailability in Ocular Drug Delivery Systems

“…Implants can also be made as stimuli-responsive delivery systems, but the currently marketed implants extended the release but do not change the rate of the drug release. There are many ongoing studies related to stimuli-responsive polymeric implants [37,[69][70][71]. Felipe et al prepared an implant for the delivery of bimatoprost for treatment of glaucoma and ocular hypertension; in a 12-week study, they showed that a bimatoprost implant was not inferior to timolol and it has potential for improved adherence and decrease the treatment of glaucoma [72].…”

Enhancement of Biological and Pharmacological Properties of an Encapsulated Polyphenol: Curcumin

“…In general the inclusion of polymers, lipids, and surfactants for the production of suitable carriers for medicinal and non-medicinal applications has been demonstrated and opportunities to produce technologies that exhibit advantages over conventional formulations including improved stability, enhanced and beneficial biodistribution profiles, altered drug release rates, lower immunotoxicity and with potential targeting of specific cells, exists [ 108 ]. Micro- and/or nano-encapsulation has been used to develop sustained/prolonged drug delivery technologies [ 30 , 109 , 110 ], minimise degradation in biological fluids [ 111 ], facilitate handling [ 112 ] reduce toxicity [ 109 , 113 , 114 , 115 ] and to improve the organoleptic properties [ 19 , 116 , 117 ] of products.…”